research about cervical cancer

Skip to Content

• Conquer Cancer
• ASCO Journals
• f Cancer.net on Facebook
• t Cancer.net on Twitter
• q Cancer.net on YouTube
• g Cancer.net on Google

Types of Cancer

• Navigating Cancer Care
• Coping With Cancer
• Research and Advocacy
• Survivorship

Cervical Cancer: Latest Research

ON THIS PAGE: You will read about the scientific research being done to learn more about cervical cancer and how to treat it. Use the menu to see other pages.

Doctors are working to learn more about cervical cancer, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your doctor about the best diagnostic and treatment options for you.

Improved detection and screening methods. Because cervical cancer is highly treatable when detected early, researchers are developing better ways to detect precancer and cervical cancer. For example, fluorescent spectroscopy is the use of fluorescent light to detect changes in precancerous cervix cells.

Human papillomavirus (HPV) prevention. As discussed in the Screening section, HPV vaccines help prevent infection from the HPV strains that cause most cervical cancers. Gardasil is also approved by the U.S. Food and Drug Administration (FDA) for boys and men ages 9 through 26 to prevent genital warts. Researchers are looking at the impact of the HPV vaccine on boys to reduce the risk of HPV transmission.

Immunotherapy. As explained in Types of Treatment , immunotherapy is a systemic therapy using medication designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. For people who already have cervical cancer, a therapeutic vaccine is being developed. This type of vaccine helps "train" the immune system to recognize cervical cancer cells and destroy them. Learn more about immunotherapy .

Fertility-preserving surgery. Research continues to focus on improving surgical techniques and finding out which patients can be treated successfully without losing their ability to become pregnant and have children. Learn more about fertility preservation .

Targeted therapy. As explained in Types of Treatment , targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Targeted drugs called angiogenesis inhibitors that block the action of a protein called vascular endothelial growth factor (VEGF) have been shown to help people live longer if they have cervical cancer that has spread to other parts of the body. VEGF promotes angiogenesis, which is the formation of new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of angiogenesis inhibitors is to “starve” the tumor. Learn more about angiogenesis inhibitors and targeted treatments .

Combination therapy. Some clinical trials are exploring different combinations of immunotherapy, radiation therapy, and chemotherapy.

Palliative and supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current cervical cancer treatments to improve comfort and quality of life for patients.

Looking for More About Latest Research?

If you would like more information about the latest areas of research in cervical cancer, explore these related items that take you outside of this guide:

To find clinical trials specific to your diagnosis, talk with your doctor or search online clinical trial databases .

Visit the Cancer.Net Blog to review news and information about cervical cancer, including research announced at recent scientific meetings.

Listen to a webinar featuring an American Society of Clinical Oncology (ASCO) expert discussing research in cervical cancer presented at the 2021 ASCO Annual Meeting.

Get updates from Cancer.Net delivered right to your inbox. Subscribe to the Inside Cancer.Net email newsletter.

Visit the website of Conquer Cancer, the ASCO Foundation , to find out how to help support cancer research. Please note that this link takes you to a different ASCO website.

The next section in this guide is Coping with Treatment . It offers some guidance on how to cope with the physical, emotional, social, and financial changes that cancer and its treatment can bring. Use the menu to choose a different section to read in this guide.

Cervical Cancer Guide

Cancer.Net Guide Cervical Cancer

• Introduction
• Medical Illustrations
• Risk Factors
• Screening and Prevention
• Symptoms and Signs
• Types of Treatment
• About Clinical Trials
• Latest Research
• Coping with Treatment
• Follow-Up Care
• Questions to Ask the Health Care Team
• Additional Resources

View All Pages

Timely. Trusted. Compassionate.

Comprehensive information for people with cancer, families, and caregivers, from the American Society of Clinical Oncology (ASCO), the voice of the world's oncology professionals.

Find a Cancer Doctor

Explore  CRI’s 2023 Cancer Research Impact

Immunotherapy For Cervical Cancer

How is immunotherapy for cervical cancer changing the outlook for patients.

Reviewed by:

Dmitriy Zamarin, MD, PhD Memorial Sloan Kettering Cancer Center

Immunotherapy for cervical cancer shows promise with preventive vaccines and new treatment directions.

Cervical cancer is the fourth most common cancer in the world for women, affecting over half a million people every year. Almost all cases of cervical cancer are associated with human papilloma virus (HPV) infection. This prevalent virus is also linked to anal, genital, and head and neck cancers. Most people infected by HPV do not develop cancers associated with the virus.

During the early stages, cervical cancer can usually be detected early with regular Pap smear, also called a Pap test, a procedure in which cells are scraped from the cervix and looked at under a microscope. Mortality rates have been decreasing in United States, thanks largely to widespread use of the Pap smear as a screening tool. In addition to the Pap smear, DNA tests can also detect HPV strains that pose a cervical cancer risk. Cervical cancer incidence and mortality, however, remain significantly higher in low-income countries.

Symptoms of this disease often go undetected until the cancer becomes invasive. Abnormal vaginal bleeding is the most common sign of cervical cancer.

There are an estimated 570,000 new cases of cervical cancer diagnosed and 310,000 cervical cancer-related deaths each year globally, and in 2023 there will be an estimated 14,000 new cases and 4,000 deaths in the United States alone. If cervical cancer is caught while it is still localized, the five-year survival rate is 92%. The five-year survival rates for patients with regional and distant disease are 57% and 17%, respectively.

Three immunotherapy vaccines (below) are FDA-approved to prevent HPV infection. Since the introduction of the first HPV vaccine in 2006, the number of new cases of cervical cancer has dropped significantly in the United States. Recent studies have begun to provide evidence that vaccination may also provide some benefit to people who have been infected previously with HPV. While these vaccines are effective in preventing HPV infection, there is no evidence that the vaccines are effective against established cancers.

Preventive Vaccines

• Cervarix®:  a vaccine approved for use in preventing infection by the two strains of HPV that cause most cervical cancers, HPV types 16 and 18; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers
• Gardasil®:  a vaccine that protects against infection by HPV types 16, 18, 6, and 11; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers
• Gardasil-9®:  a vaccine approved for the prevention of infection by HPV types 16, 18, 31, 33, 45, 52, and 58, and for the prevention of genital warts caused by HPV types 6 or 11; can help prevent the development of HPV-related cervical, vulvar, vaginal, and anal cancers

Cervical Cancer Treatment Options

Standard treatment options for cervical cancer are surgery, radiation therapy, chemotherapy, and targeted therapy.

Immunotherapy  is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently three FDA-approved immunotherapy options for the treatment of cervical cancer.

Targeted Antibodies

• Bevacizumab (Avastin®):  a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced cervical cancer in combination with chemotherapy
• Tisotumab vedotin (Tivdak™):  an antibody-drug conjugate that targets tissue factor (TF); approved for subsets of patients with advanced cervical cancer

Immunomodulators

• Pembrolizumab (Keytruda®):  a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced cervical cancer that has PD-L1 expression, high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)

Other vaccines and immunotherapies that target HPV-infected tumors are also currently being tested in clinical trials.

CRI’s Impact in Cervical Cancer

Since 1953, the Cancer Research Institute has dedicated more than $10 million in funding to develop and discover immunotherapies that can treat gynecologic cancers, including cervical cancer. CRI’s support of cervical cancer and human papillomavirus research has led to several breakthroughs in treatment, including paving the way for more effective prevention methods.

• In 1999, CRI awarded the first of several grants to  Ian H. Frazer, MD, FRCPA , for work on “virus-like particles” (VLP) based papillomavirus vaccines—crucial to the development of the first preventive cervical cancer vaccine, Gardasil®.

“This new vaccine that prevents cervical cancer grew out of research funded by CRI.” Professor Ian Frazer, 2003 CRI Annual Report

• In 2009, Sjoerd van der Burg, PhD, and Cornelis (Kees) Melief, MD, PhD, at Leiden University Medical Center,  found in a CRI-sponsored study that a vaccine composed of HPV long peptides could result in durable complete responses  in some women with HPV 16+ vulvar intraepithelial neoplasias (VINs), a disease that normally has a spontaneous regression rate of less than 2%.
• In 2014, W. Martin Kast, PhD, was awarded a Clinic and Laboratory Integration Program (CLIP) grant from CRI to test a treatment that combines chemoradiation and the immunotherapy ipilimumab (Yervoy®) to trigger a targeted immune attack against cervical cancer cells and lead to a much-needed treatment for cervical cancer patients.
• In 2020, Sjoerd van der Burg, PhD, and Cornelis (Kees) Melief, MD, PhD, at Leiden University Medical Center, revealed the benefits of a vaccine-chemotherapy combination in advanced, HPV-associated cervical cancer.

You can explore  CRI’s current funding for cervical cancer research  in our funding directory.

4th Most frequently diagnosed cancer of women worldwide

91% 5-year survival rate for localized disease

$12 Million Awarded by CRI to cervical cancer research

570K Newly diagnosed patients each year globally

Cervical Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in cervical cancer clinical trials include:

• EGFR:  a pathway that controls cell growth and is often mutated in cancer
• HER2:  a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
• Tissue Factor (TF):  a protein expressed by cancer cells that aids proliferation and metastasis
• TROP2 : a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
• VEGF/VEGF-R:  a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in cervical cancer clinical trials include:

• Folate-related proteins:  proteins in this pathway are commonly overexpressed in cancer
• Human Papilloma Virus (HPV)-related antigens:  foreign viral proteins expressed by HPV-infected cancer cells
• Personalized neoantigens:  these abnormal markers arise from mutations and are expressed exclusively by tumor cells
• Tumor-associated antigens (TAAs):  proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in cervical cancer clinical trials include:

• GD2:  a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
• MAGE antigens:  the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system
• Mesothelin:  a protein that is commonly overexpressed in cancer and may aid metastasis
• MUC-1:  a sugar-coated protein that is commonly overexpressed in cancer

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in cervical cancer clinical trials include:

• CD73 or A2AR:  blocking these pathways can help prevent the production of immunosuppressive adenosine
• CD137 (also known as 4-1BB):  activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
• CSF1/CSF1R:  blocking this pathway can help reprogram cancer-supporting macrophages
• CTLA-4:  blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
• CXCR4:  blocking this pathway can promote the migration and recruitment of immune cells
• GITR:  activating this pathway can help prevent immunosuppression and increase the survival of cancer-fighting T cells
• ICOS:  activating this co-stimulatory pathway on T cells can help enhance immune responses against cancer
• IDO:  blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
• IL-2/IL-2R:  activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
• OX40:  activating this co-stimulatory pathway can help promote T cell survival after activation
• PD-1/PD-L1:  blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
• Toll-like receptors (TLRs):  activation of these innate immune receptors can help stimulate immune responses against tumors

Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in cervical cancer clinical trials include:

• Adenovirus:  a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
• Measles virus:  a highly contagious virus that infects the respiratory tract and can cause measles
• New Castle Virus:  a virus primarily found in birds; can cause mild conjunctivitis and flu-like symptoms in humans
• Vaccinia virus:  the virus that was used to help vaccinate against and eliminate smallpox; rarely causes illness in humans and is associated with a rash covering the body
• Vesicular stomatitis virus:  a virus that belongs to the same family as the rabies virus; can cause flu-like symptoms in humans

Find an Immunotherapy Clinical Trial

Create a profile and fill out a questionnaire to identify immunotherapy clinical trials for which you may be eligible.

Need more information? Learn more about clinical trials .

News & Events

AACR 2022 Recap: T Cells Still On Top, But Make Room for Myeloid Cells

#Immune2Cancer Day 2022

On Friday, June 10, 2022, we invite you to raise awareness of the lifesaving potential of immunotherapy.

Giving Tuesday 2022

Be a part of the global generosity movement and celebrate all acts of giving. #GivingTuesday

This website uses tracking technologies, such as cookies, to provide a better user experience. If you continue to use this site, then you acknowledge our use of tracking technologies. For additional information, review our Privacy Policy .

What Is Cervical Cancer?

Cervical cancer is cancer that starts in the cells of the cervix. The cervix is the lower, narrow end of the uterus (womb). The cervix connects the uterus to the vagina (birth canal). Cervical cancer usually develops slowly over time. Before cancer appears in the cervix, the cells of the cervix go through changes known as dysplasia, in which abnormal cells begin to appear in the cervical tissue . Over time, if not destroyed or removed, the abnormal cells may become cancer cells and start to grow and spread more deeply into the cervix and to surrounding areas.

The cervix has two main parts:

• The ectocervix (also called exocervix) is the outer part of the cervix that can be seen during a gynecologic exam. The ectocervix is covered with thin, flat cells called squamous cells .
• The endocervix is the inner part of the cervix that forms a canal that connects the vagina to the uterus. The endocervix is covered with column-shaped glandular cells that make mucus .

The squamocolumnar junction (also called the transformation zone) is the border where the endocervix and ectocervix meet. Most cervical cancers begin in this area.

Types of cervical cancer

Cervical cancers are named after the type of cell where the cancer started. The two main types are:

• Squamous cell carcinoma : Most cervical cancers (up to 90%) are squamous cell carcinomas. These cancers develop from cells in the ectocervix.
• Adenocarcinoma : Cervical adenocarcinomas develop in the glandular cells of the endocervix. Clear cell adenocarcinoma, also called clear cell carcinoma or mesonephroma, is a rare type of cervical adenocarcinoma.

Sometimes, cervical cancer has features of both squamous cell carcinoma and adenocarcinoma. This is called mixed carcinoma or adenosquamous carcinoma. Very rarely, cancer develops in other cells in the cervix.

Learn more about cervical cancer

Many cervical cancer symptoms are also seen with other, less serious conditions. These are the warning signs you shouldn’t ignore.

Causes, Risk Factors, and Prevention

Long-lasting HPV infection causes almost all cervical cancers. Learn about HPV infection and other risk factors for cervical cancer and what you can do to lower your risk.

If you have a cervix, screening for cervical cancer is an important part of routine health care. Learn when to get screened and what to expect during and after screening.

HPV and Pap Test Results

Learn what HPV and Pap test results mean and next steps if a test result is abnormal.

Learn about the tests that are used to diagnose and stage cervical cancer.

Prognosis and Survival Rates

Learn about cervical cancer survival rates and why this statistic doesn't predict exactly what will happen to you.

Stage refers to the extent of your cancer, such as how large the tumor is and if it has spread. Learn about cervical cancer stages, an important factor in deciding your treatment plan.

Learn about the different ways cervical cancer can be treated.

Childhood Cervical and Vaginal Cancers

Cervical cancer and vaginal cancer are very rare in children. Learn about the signs and symptoms, diagnosis, and treatment options.

Coping and Support

Certain aspects of cervical cancer diagnosis and treatment are of special concern. Gain a greater sense of control by knowing what to expect and what resources are available to help you cope.

• Intellectual Property
• Connect with Us
• Publications
• Clinical Trials

INFORMATION FOR

• Residents & Fellows
• Researchers

Genetic Analysis of Rare, Often Deadly Cervical Cancer Uncovers Potential Treatments

Largest translational study seeking novel treatments specifically for neuroendocrine tumors of the cervix (netc)., microscopic image of cervical cancer.

This was the largest translational study seeking novel treatments specifically for neuroendocrine tumors of the cervix (NETc).

An ambitious study of patients from around the world with rare neuroendocrine tumors of the cervix (NETc) set out to uncover potential treatments by understanding the molecular basis of the aggressive disease. Since the average survival for patients diagnosed with NETc is less than two years, effective treatments are needed.

Yale Cancer Center (YCC) researchers at Yale School of Medicine (YSM) analyzed the genetic landscape of 66 tumors, the largest series of cervical NET ever reported in scientific literature. They used cutting-edge techniques (whole-exome and RNA-Seq analysis) to sequence all the genes from the tumors and identified the mutations that are crucial for these tumors to grow and endure cancer treatment.

The study, conducted through international collaboration with research groups in Italy, Norway, South Korea, and the United States, revealed atypical genes and pathways that indicate NET patients could benefit from precision medicine. Researchers say the findings better define the genetic landscape of NETc and suggest that a large subset of these highly aggressive malignancies might respond to existing targeted therapies.

The study was published April 15 in Proceedings of the National Academy of Sciences .

“Our findings have important implications for the development of novel therapies since NETc are currently treated with chemotherapy regimens used for patients with lung cancer,” said senior author Alessandro Santin, MD , co-chief of the division of gynecologic oncology at YCC and a professor of obstetrics, gynecology & reproductive sciences at YSM. “Our genetic data suggest that regimens used for the most common types of cervical cancer in combination with immunotherapies may represent a better choice.”

Stefania Bellone, PhD , first author of the study and associate research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at YSM, said that the genetic sequencing of tumors with both adenocarcinoma and neuroendocrine elements found for the first time that the neuroendocrine part of the tumor comes from the same type of cell that leads to the adenocarcinoma, meaning they each have similar genetic mutations typical of epithelial cancer.

The study team sequenced tumor genes from 64 patients affected with NETc, including two patients with NETc tumors mixed with adenocarcinoma cells, cancer cells that form in glands that line certain organs. Using two fully sequenced patient-derived xenografts (PDX) — in which patients’ cancer cells were implanted in mice — the researchers identified mutations that were crucial for the tumors to grow and survive treatment. The team also studied genes that were not mutated but were amplified in the tumors to give them a growth advantage over normal tissues.

The findings showed many genes had repeated mutations and some had higher levels of certain genetic changes than others. Tumors with a higher number of mutations are potentially more sensitive to immunotherapy.

Corresponding author Joseph Schlessinger, PhD , the William H. Prusoff Professor of Pharmacology at YSM, said that creating two PDX models, each with their own mutation profile, allowed testing of each to determine if they could predict drug responses in living organisms. The approach held promise for tailoring cancer treatments to individual patients.

Other Yale authors on the study include Blair McNamara , Michelle Greenman , Levent Mutlu , Cem Demirkiran , Tobias Max Philipp Hartwich , Yang Yang-Hartwich , Natalia Buza , Pei Hui , Gary Altwerger , Gloria Huang , Vaagn Andikyan , Mitchell Clark , Elena Ratner , Masoud Azodi , Peter E. Schwartz , and Ludmil B. Alexandrov

Featured in this article

• Alessandro Santin, MD
• Stefania Bellone, PhD
• Joseph Schlessinger, PhD
• Blair Colette McNamara, MD
• Michelle Greenman
• Levent Mutlu, MD
• Cem Demirkiran, MD
• Tobias Hartwich, PhD
• Yang Yang, PhD
• Natalia Buza, MD
• Pei Hui, PhD, MD
• Gary Altwerger, MD
• Gloria Huang, MD, FACOG
• Vaagn Andikyan, MD
• Mitchell Clark, MD, MPH
• Peter Schwartz, MD
• Elena Ratner, MD, MBA
• Ludmil B. Alexandrov, PhD
• Masoud Azodi, MD

• Patient Care & Health Information
• Diseases & Conditions
• Cervical cancer
• What is cervical cancer? A Mayo Clinic expert explains

Learn more about cervical cancer from Mayo Clinic gynecologic oncologist Kristina Butler, M.D., M.S.

I'm Dr. Kristina Butler, a gynecologic oncologist at Mayo Clinic. In this video, we'll cover the basics of cervical cancer: What is it? Who gets it? The symptoms, diagnosis, and treatment. Whether you're looking for answers for yourself or someone you love, we're here to give you the best information available. Cervical cancer happens when cells in the cervix, the lower part of the uterus that connects to the vagina, start to become abnormal. Small changes in the cell DNA tells them to multiply out-of-control, and cells accumulate in growths called tumors. Thankfully, advances in medical technology and specifically the use of Pap tests, have significantly helped us identify cervical cancer in patients earlier than ever before. What was once the most common cause of cancer death for American women is now caught sooner and therefore more curable.

While it isn't perfectly clear what sparks the cervical cells to change their DNA, it is certain that human papilloma virus, or HPV, plays a role. HPV is spread by skin to skin contact often during sexual encounters. Over 85% of the general population has been exposed. But most people with HPV never develop cervical cancer. However, reducing your risk of one helps reduce your risk of the other. I recommend getting both the HPV vaccine and regular screening tests. Other risk factors for cervical cancer include multiple sexual encounters. But it only takes one to contract HPV, so it's important to always practice safe sex. A weakened immune system and also smoking are linked to higher risk. One drug called DES was popular in the 1950s as a miscarriage prevention drug. So if your mother took it while pregnant, you may have higher risk as well.

Unfortunately, the early stages of cervical cancer generally show no signs or symptoms. And this is why we emphasize getting Pap smears every three to five years and yearly pelvic exams. Once the cancer has progressed, it can show these symptoms: Unusual vaginal bleeding, for example, after intercourse or between periods or after menopause. Watery, bloody vaginal discharge that may be heavy or have an odor. And pelvic pain or other pain can also occur during intercourse.

Most guidelines suggest starting regular screening for cervical cancer at age 21. And during these screenings, a provider collects cells from the cervix to be tested in the lab. HPV DNA tests examine the cell specifically for HPV that can lead to pre-cancer. A Pap test, or commonly called a Pap smear, tests the cells for abnormalities. The process of these tests are not painful but can be mildly uncomfortable. If your provider suspects cervical cancer, they may start a more thorough examination of the cervix. This may include a colposcopy, which is a special tool that shines light through the vagina into the cervix to magnify the view for your provider. During the colposcopy, your provider might take several deeper samples of cells to examine. This could include a punch biopsy that collects tiny samples of cells, or an endocervical curettage that uses a narrow instrument to take an internal tissue sample. And if after further examination, the sample tissue is worrisome, your doctor may run more tests or collect other tissue samples from deeper layers of the cells. This could use a LEEP or cone biopsy procedure to give the clearest picture possible.

Treating cervical cancer isn't one-size-fits-all. Your doctor will consider the whole picture of your health and your personal preferences before making a recommendation. And this will include one or several treatment methods. For early cervical cancer, we typically treat with surgery to remove the abnormal growths. For more advanced cervical cancer, there's also chemotherapy, a drug that runs the body killing cancer cells in its path. Radiation therapy uses high-powered beams with energy focused on the cancer cells. There's also targeted drug therapy that blocks specific weaknesses present within the cancer cells. And immune therapy, a drug treatment that helps your immune system recognize cancer cells and attack them.

No one can be prepared for a cancer diagnosis. However, there are ways we can help reduce anxiety and feel more in control of the situation. Learning about the condition can make you feel more empowered and confident in the decisions about your care. So ask lots of questions and request additional resources. Find support. Ask for help from your family and friends. If you feel more comfortable expressing yourself in a support group, there are many available both online and in-person. Set goals that you can achieve and feel good about. And most importantly, take care of yourself. This time can be difficult and fatiguing. Eat well, relax and get enough rest. If you'd like to learn even more about cervical cancer, watch our other related videos or visit mayoclinic.org. We wish you well.

Cervical cancer begins in the cells of the cervix.

Cervical cancer is a growth of cells that starts in the cervix. The cervix is the lower part of the uterus that connects to the vagina.

Various strains of the human papillomavirus, also called HPV, play a role in causing most cervical cancers. HPV is a common infection that's passed through sexual contact. When exposed to HPV , the body's immune system typically prevents the virus from doing harm. In a small percentage of people, however, the virus survives for years. This contributes to the process that causes some cervical cells to become cancer cells.

You can reduce your risk of developing cervical cancer by having screening tests and receiving a vaccine that protects against HPV infection.

When cervical cancer happens, it's often first treated with surgery to remove the cancer. Other treatments may include medicines to kill the cancer cells. Options might include chemotherapy and targeted therapy medicines. Radiation therapy with powerful energy beams also may be used. Sometimes treatment combines radiation with low-dose chemotherapy.

Products & Services

• A Book: Mayo Clinic Family Health Book, 5th Edition
• A Book: Taking Care of You

Female reproductive system

The ovaries, fallopian tubes, uterus, cervix and vagina (vaginal canal) make up the female reproductive system.

When it starts, cervical cancer might not cause symptoms. As it grows, cervical cancer might cause signs and symptoms, such as:

• Vaginal bleeding after intercourse, between periods or after menopause.
• Menstrual bleeding that is heavier and lasts longer than usual.
• Watery, bloody vaginal discharge that may be heavy and have a foul odor.
• Pelvic pain or pain during intercourse.

When to see a doctor

Make an appointment with a doctor or other health care professional if you have any symptoms that worry you.

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

From Mayo Clinic to your inbox

Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. Click here for an email preview.

Error Email field is required

Error Include a valid email address

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

Thank you for subscribing!

You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox.

Sorry something went wrong with your subscription

Please, try again in a couple of minutes

• Where cervical cancer begins

Two types of cells line the surface of the cervix, and both can become cancerous. Glandular cells have a column-shaped appearance. Squamous cells are thin and flat. The boundary between the two types of cells is where most cervical cancers start.

Cervical cancer begins when healthy cells in the cervix develop changes in their DNA . A cell's DNA contains the instructions that tell a cell what to do. The changes tell the cells to multiply quickly. The cells continue living when healthy cells would die as part of their natural life cycle. This causes too many cells. The cells might form a mass called a tumor. The cells can invade and destroy healthy body tissue. In time, the cells can break away and spread to other parts of the body.

Most cervical cancers are caused by HPV . HPV is a common virus that's passed through sexual contact. For most people, the virus never causes problems. It usually goes away on its own. For some, though, the virus can cause changes in the cells that may lead to cancer.

Types of cervical cancer

Cervical cancer is divided into types based on the type of cell in which the cancer begins. The main types of cervical cancer are:

• Squamous cell carcinoma. This type of cervical cancer begins in thin, flat cells, called squamous cells. The squamous cells line the outer part of the cervix. Most cervical cancers are squamous cell carcinomas.
• Adenocarcinoma. This type of cervical cancer begins in the column-shaped gland cells that line the cervical canal.

Sometimes, both types of cells are involved in cervical cancer. Very rarely, cancer occurs in other cells in the cervix.

Risk factors

Risk factors for cervical cancer include:

• Smoking tobacco. Smoking increases the risk of cervical cancer. When HPV infections happen in people who smoke, the infections tend to last longer and are less likely to go away. HPV causes most cervical cancers.
• Increasing number of sexual partners. The greater your number of sexual partners, and the greater your partner's number of sexual partners, the greater your chance of getting HPV .
• Early sexual activity. Having sex at an early age increases your risk of HPV .
• Other sexually transmitted infections. Having other sexually transmitted infections, also called STI s, increases the risk of HPV , which can lead to cervical cancer. Other STI s that increase the risk include herpes, chlamydia, gonorrhea, syphilis and HIV / AIDS .
• A weakened immune system. You may be more likely to develop cervical cancer if your immune system is weakened by another health condition and you have HPV .
• Exposure to miscarriage prevention medicine. If your parent took a medicine called diethylstilbestrol, also known as DES, while pregnant, your risk of cervical cancer might be increased. This medicine was used in the 1950s to prevent miscarriage. It's linked to a type of cervical cancer called clear cell adenocarcinoma.

To reduce your risk of cervical cancer:

• Ask your doctor about the HPV vaccine. Receiving a vaccination to prevent HPV infection may reduce your risk of cervical cancer and other HPV -related cancers. Ask your health care team if an HPV vaccine is right for you.
• Have routine Pap tests. Pap tests can detect precancerous conditions of the cervix. These conditions can be monitored or treated in order to prevent cervical cancer. Most medical organizations suggest beginning routine Pap tests at age 21 and repeating them every few years.
• Practice safe sex. Reduce your risk of cervical cancer by taking measures to prevent sexually transmitted infections. This may include using a condom every time you have sex and limiting the number of sexual partners you have.
• Don't smoke. If you don't smoke, don't start. If you do smoke, talk to a health care professional about ways to help you quit.

More Information

Cervical cancer care at Mayo Clinic

• Cervical cancer FAQs

Living with cervical cancer?

Connect with others like you for support and answers to your questions in the Gynecologic Cancers support group on Mayo Clinic Connect, a patient community.

Gynecologic Cancers Discussions

9 Replies Thu, Apr 18, 2024

56 Replies Wed, Apr 17, 2024

12 Replies Mon, Apr 15, 2024

• Cervical cancer. Cancer.Net. https://www.cancer.net/cancer-types/cervical-cancer/view-all. Accessed March 27, 2023.
• Gershenson DM, et al. Malignant diseases of the cervix. In: Comprehensive Gynecology. 8th ed. Elsevier; 2022. https://www.clinicalkey.com. Accessed March 27, 2023.
• Niederhuber JE, et al., eds. Cancers of the cervix, vulva and vagina. In: Abeloff's Clinical Oncology. 6th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed March 27, 2023.
• Cervical cancer. National Comprehensive Cancer Network. ps://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426. Accessed March 27, 2023.
• AskMayoExpert. Cervical cancer screening (adult). Mayo Clinic; 2022.
• Palliative care. National Comprehensive Cancer Network. https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1454. Accessed March 27, 2023.
• What is cervical cancer? National Cancer Institute. https://www.cancer.gov/types/cervical. Accessed March 27, 2023.
• Cervical dysplasia: Is it cancer?
• Cone biopsy

Associated Procedures

• Brachytherapy
• Chemotherapy
• Palliative care
• Radiation therapy

News from Mayo Clinic

• Mayo Clinic Minute: Why Black women need to be screened for cervical cancer Jan. 25, 2024, 05:00 p.m. CDT
• Toolkit for reducing cervical cancer risk Jan. 23, 2024, 04:30 p.m. CDT
• Mayo Clinic Minute: Cervical cancer screening Jan. 08, 2024, 03:31 p.m. CDT
• Cervical cancer and HPV -- what's the connection? Jan. 02, 2024, 04:00 p.m. CDT
• Mayo Clinic Health System now offering Saturday appointments for cervical cancer screening June 14, 2023, 05:15 p.m. CDT
• Mayo Clinic Minute: Screening for cervical cancer Jan. 12, 2023, 05:30 p.m. CDT
• Mayo Clinic Q and A: Cervical cancer and HPV screening Jan. 11, 2023, 04:00 p.m. CDT
• 4 ways to reduce risks of cervical cancer Jan. 10, 2023, 03:00 p.m. CDT

Mayo Clinic in Rochester, Minnesota, has been ranked among the best Gynecology hospitals in the nation for 2023-2024 by U.S. News & World Report.

• Symptoms & causes
• Diagnosis & treatment
• Doctors & departments
• Care at Mayo Clinic

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book

Make twice the impact

Your gift can go twice as far to advance cancer research and care!

Select "Patients / Caregivers / Public" or "Researchers / Professionals" to filter your results. To further refine your search, toggle appropriate sections on or off.

Home > Patients, Caregivers, and Advocates > About Cancer > Cancers > Cervical Cancer

Cervical Cancer

Cervical cancer usually develops slowly over time. Before cancer appears in the cervix, the cells of the cervix go through changes known as dysplasia, in which abnormal cells begin to appear in the cervical tissue. Those abnormal cells may become cancer cells and start to grow and spread more deeply into the cervix and to surrounding areas.

Infection of the cervix with human papillomavirus (HPV) is almost always the cause of cervical cancer. Not all women with HPV infection, however, will develop cervical cancer. Women who do not regularly have tests to detect HPV or abnormal cells in the cervix are at increased risk of cervical cancer. The vast majority of cervical cancers could be prevented with Pap tests and HPV vaccination.

Cervical cancer, an often preventable cancer, will be diagnosed in an estimated 13,960 women living in the United States in 2023, and some 4,310 women are expected to die of the disease, according to the National Cancer Institute.

about cervical cancer

Cervical cancer is a disease in which cancer cells arise in the cervix, which connects the uterus to the vagina. HPV is almost always the cause of cervical cancer, which is why vaccines against the virus are an important part of cervical cancer prevention strategies. 

The U.S. Food and Drug Administration (FDA) has approved three vaccines – Gardasil, Gardasil 9, and Cervarix – that prevent infection with certain subtypes of HPV including 16 and 18, two high-risk HPVs that cause some 70 percent of cervical cancers. 

In a study published in Cancer Epidemiology, Biomarkers & Prevention , a journal of the American Association for Cancer Research (AACR), researchers investigated the types of HPV infections in 12,514 women aged 15 to 45 and found that the seven subtypes of the virus targeted by Gardasil 9 accounted for about 91 percent of the most advanced cervical precancers, meaning that Gardasil 9 could prevent nine out of 10 cases of cervical cancer.

“If vaccination programs with this new-generation vaccine are effectively implemented, approximately 90 percent of invasive cervical cancer cases worldwide could be prevented, in addition to the majority of precancerous lesions,” said senior author Elmar A. Joura, MD , an associate professor of gynecology at the Medical University of Vienna in Austria .

But there is a lack of public awareness and adherence to vaccination programs in the U.S. The Centers for Disease Control and Prevention (CDC) recommends vaccination for girls and boys ages 11 to 12. 

A 2015 article in Cancer Epidemiology, Biomarkers & Prevention  reported on a national survey that found many pediatricians and primary care physicians communicate about HPV vaccination in ways that may discourage parents from getting their children vaccinated. 

“We are currently missing many opportunities to protect today’s young people from future HPV-related cancers,” said Melissa B. Gilkey, PhD, the article’s lead author and an assistant professor of population medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. 

Usually, cervical cancer develops slowly over time, and another powerful preventive measure is Pap test screening, a procedure during which cells are collected from the surface of the cervix and examined. The Pap test can both detect cancer at an early stage, when treatment outcomes tend to be better, and detect precancerous abnormalities, which can then be treated to prevent them from developing into cancers.

Source: National Cancer Institute

You can support the AACR's mission by contacting your representatives and senators and advocating for increased funding for lifesaving cancer research.

FDA Approvals in Oncology: January-March 2024 

My Name is Mom. And I Have Cancer.

Expanding Global Access to Cervical Cancer Prevention, Screening, and Treatment 

• January is Cervical Cancer Awareness Month
• A New HPV Vaccine May Prevent More Cervical...
• Expanding Global Access to Cervical Cancer...

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts

Cervical cancer articles within Nature Reviews Clinical Oncology

Research Highlight | 02 April 2024

Pembrolizumab plus chemoradiotherapy effective in locally advanced cervical cancer

• Peter Sidaway

Research Highlight | 06 March 2024

Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer

• Diana Romero

Research Highlight | 18 December 2023

Neoadjuvant chemoimmunotherapy is effective in locally advanced cervical cancer

Research Highlight | 25 February 2022

Benefit with cemiplimab in cervical cancer

Research Highlight | 06 October 2021

Pembrolizumab tunes up chemotherapy in cervical cancer

Research Highlight | 29 January 2021

SCRT for early stage cervical cancer

• David Killock

In Brief | 20 December 2018

TIL infusions effective in HPV-associated cancers

Research Highlight | 21 November 2018

Less invasive is not always better

News & Views | 11 April 2017

Novel molecular subtypes of cervical cancer — potential clinical consequences

The Cancer Genome Atlas Research Network recently published the most comprehensive, multi-omic molecular characterization of cervical cancers performed to date. The data reveal novel disease subtypes, and provide new insights into the aetiology and pathogenesis of cervical cancer. Importantly, the information obtained has potentially major clinical implications.

• Chris J. L. M. Meijer
•  &  Renske D. M. Steenbergen

Research Highlight | 13 October 2015

Therapeutic HPV vaccine holds promise

Opinion | 01 September 2015

HPV-FASTER: broadening the scope for prevention of HPV-related cancer

Human papillomavirus (HPV)-screening technologies and HPV vaccination are revolutionizing the management of cancers related to this virus, in particular, cervical neoplasms. At present, however, the effectiveness of these modalities is not optimal, owing to the limited scope of HPV-vaccination and cervical screening programmes. In this Perspectives, an international panel of experts describes for the first time a new campaign, termed 'HPV-FASTER', which aims to broaden the use of HPV vaccination coupled with HPV testing to women aged up to 30 years, and in some settings up to 50 years, with the aim of accelerating the reduction in the incidence of HPV infections and cervical cancer. The authors describe the evidence supporting this approach and details on how it might be implemented, discuss the opportunities—particularly in low-resource settings—and challenges associated with the strategy, and highlight key research gaps that need to be addressed in future studies.

• F. Xavier Bosch
• , Claudia Robles
•  &  Jack Cuzick

In Brief | 23 June 2015

Less than three doses of HPV-16/18 prevents HPV infection

News & Views | 02 June 2015

Squamocolumnar junction ablation—tying up loose ends?

Despite the commercialization of HPV vaccines, cervical cancer remains a major cause of death, especially in developing countries. Recent data implicate a discrete population of cells within the cervical squamocolumnar junction in the pathogenesis of cervical precancerous lesions, indicating that ablation of these cells might reduce the rate of cervical cancer in high-risk populations.

• Michael Herfs
•  &  Christopher P. Crum

News & Views | 24 February 2015

New standard of care—HPV testing for cervical cancer screening

High-risk human papillomavirus (hrHPV) types cause cervical cancer. Hence, a negative hrHPV test provides excellent reassurance against cervical precancer and cancer, superior to a negative cervical smear (Papanicolaou or Pap) test. Screening first for hrHPV might improve the accuracy and positive predictive value of secondary Pap testing in hrHPV-positive women, and thus guide decisions on what care is needed.

• Philip E. Castle

Research Highlight | 17 February 2015

Survival benefit and quality of life

• Lisa Hutchinson

Research Highlight | 09 December 2014

From ENA 2014

News & Views | 08 April 2014

Further delineating bevacizumab's response spectrum

The use of antiangiogenic drugs, such as bevacizumab, represents an appealing intervention against cancer. However, not all malignancies are equally responsive to such treatment. Recent trials demonstrate the efficacy of this drug for advanced-stage cervical cancer and, despite limitations, bevacizumab provides an important clinical respite for most patients with progressive glioblastoma.

• David A. Reardon
•  &  Patrick Y. Wen

Year in Review | 21 January 2014

Screening comes of age and treatment progress continues

In 2013, studies confirmed that HPV infection of target cells predisposes to cervical (pre)cancer. In developed countries, HPV screening revealed superior protection than cytology screening. In India, visual inspection of the cervix after acetic acid application significantly reduced cervical cancer mortality after 12 years. Improved survival for women with advanced disease was observed after adjuvant bevacizumab.

•  &  Peter J. F. Snijders

In Brief | 30 July 2013

Declining use of brachytherapy for cervical cancer in USA

Research Highlight | 18 June 2013

Advances in cervical cancer screening and treatment

• Rebecca Kirk

Review Article | 04 June 2013

Clinical trials of human papillomavirus vaccines and beyond

Highly efficacious vaccines are available to protect against persistent human papillomavirus (HPV) infection and, therefore, the associated neoplasias (most notably cervical cancer). This Review article discusses the two approved vaccines in terms of their structure, mode of action, efficacy, cross-reactivity with non-vaccine HPV types, safety and use in vaccination programmes.

• Matti Lehtinen
•  &  Joakim Dillner

News & Views | 11 September 2012

Cervical cancer—should we abandon cytology for screening?

Convincing data have shown that human papillomavirus (HPV)-DNA testing predicts the development of high-grade cervical cancer better than cytology. However, for HPV-positive women, triage with cytology testing should be performed before colposcopy. The question on how to proceed if the cytology test in HPV-positive women is negative remains unclear.

•  &  Johannes Berkhof

News & Views | 14 February 2012

More evidence supporting human papillomavirus testing

Clinical trials have consistently demonstrated the superior sensitivity of human papillomavirus (HPV) testing compared with cytology (Pap) testing for identifying women at risk of cervical cancer. Rijkaart et al . have now shown that adding HPV testing to routine cervical cancer screening can further reduce the risk of cervical cancer compared to Pap testing alone.

Research Highlight | 06 September 2011

Cisplatin more effective when given less often

News & Views | 31 May 2011

New treatment paradigm for locally advanced cervical cancer?

Despite the improved progression-free survival and overall survival demonstrated by cisplatin–gemcitabine chemoradiation in a phase III randomized trial in patients with stage IIB to IVA cervical cancer, the acute and chronic toxic effects urge caution before embracing this as a new treatment paradigm.

• Peter G. Rose

News & Views | 01 July 2010

HPV testing for cervical cancer: the good, the bad, and the ugly

A randomized, controlled trial has shown human papillomavirus (HPV) DNA testing with and without liquid-based cytology to be more sensitive but less specific than conventional Papanicolaou smears for detection of precancerous lesions of the cervix. The lead-time advantage of early detection of precancerous lesions by HPV DNA testing resulted in cervical cancer reduction; however, an increased detection of possibly regressive precancerous lesions could result in unnecessary treatment, especially in women aged 25–34 years.

News & Views | 01 February 2010

Cisplatin combinations in cervical cancer—which is best?

We reviewed the results of the Gynecological Oncology Group 204 (GOG-204) randomized phase III trial, which investigated four cisplatin combination chemotherapy regimens for the treatment of patients with recurrent or metastatic cervical carcinoma. As the overall survival was similar between all arms, treatment recommendations need to be tailored based on toxic effects.

• David O. Holtz
•  &  Charles J. Dunton

Research Highlight | 01 January 2010

IL-12 polymorphism linked to cervical cancer risk

• Vessela Vassileva

Browse broader subjects

• Gynaecological cancer

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

UC to open national trial to study self-testing for HPV, cervical cancer

New method could improve access, early detection and treatment to underserved populations.

Cervical cancer is preventable through vaccination for human papillomavirus (HPV) and treatable through early detection. But the National Cancer Institute (NCI) reports more than half of all cervical cancer cases diagnosed in the United States occur in patients who have never been screened or are infrequently screened. 

Barriers to screening include socioeconomic factors, a lack of awareness and a lack of access, whether patients are physically far from a clinic or do not seek care due to being uninsured or underinsured. 

To help close the gap in access to screening, the NCI has launched the Cervical Cancer ‘Last Mile’ Initiative , a public-private partnership working to provide evidence on the effectiveness and accuracy of self-testing for HPV. 

Part of this initiative is the SHIP trial (Self-collection for HPV testing to Improve Cervical Cancer Prevention). The University of Cincinnati Cancer Center is one of 25 SHIP trial sites across the country testing whether samples self-collected by patients for HPV testing are as accurate and effective as clinic-collected samples. 

Leeya Pinder, MD. Photo/University of Cincinnati.

Leeya Pinder, MD, local principal investigator of the trial, said there are several ways to screen for cervical cancer. But primary HPV testing, rather than other methods including Pap and HPV cotesting, shows the most promise for being an effective self-testing method. 

“It really gives people the opportunity to just do a vaginal swab or a cervico-vaginal swab so that they can get tested for high-risk HPV, which is usually the driver of cervical precancer and cervical cancer,” said Pinder, a Cancer Center member and associate professor in the UC College of Medicine Department of Obstetrics and Gynecology, Division of Gynecologic Oncology. “What we’ve been trying to do over the last several years is prove that women can actually do HPV testing on their own.” 

While other countries have approved self-collection HPV testing, the method is not currently approved by the U.S. Food and Drug Administration. Pinder said previous studies have shown self-testing methods are effective, especially for certain underscreened populations. 

“Those populations include those who sometimes struggle with substance abuse, sometimes have a history of trauma or other kinds of abuse, those that are concerned about their immigration status or actually, many things,” she said. “These are reaching the people who for whatever reason do not have great access to a health care provider to get their cervical cancer screening.” 

In the SHIP trial, patients who already have a scheduled appointment for a colposcopy, an examination of the cervix, vagina and vulva, will self-test in the clinic before providers collect samples for HPV testing and continue with their routine scheduled procedure as they normally would.  

“These patients are getting two swabs, so the goal is to provide additional data that this works so that the FDA has more evidence by which to approve self-testing as a means by which we could actually target populations with limited access,” Pinder said. 

In addition to self-testing potentially increasing access to cervical cancer screening, prevention and early detection and treatment, Pinder said she is excited at the potential to personalize outreach and education to individual communities’ unique population and needs.

Pinder said health care providers could streamline care and offer connections to services, including HPV vaccinations, if self-testing is approved. Photo/iStock/anilakkus.

“I think that it will provide us an opportunity to reach people by partnering with other outreach organizations such as the 513 Relief Bus , mobile mammography vans , church events,” Pinder said. “I really think it will provide us an opportunity to reach the masses.” 

If self-testing is approved, Pinder noted health care providers will need to streamline communications procedures and link patients to care. This could look like follow-ups with clear next steps for those found to be HPV positive and/or at higher risk for cervical cancer and offering easy-to-access HPV vaccinations for those whose self-tests are negative. 

“I think that it opens a lot of doors for us in terms of education, getting people screened and then figuring out how to link people to efficient care and provide opportunities,” she said. 

Since the SHIP trial will enroll patients already scheduled to come into the clinic, community members cannot enroll themselves. However, Pinder said the Cancer Center is working to launch additional research studying HPV self-testing. This may include an early intervention program at the emergency department and comparing mail-in testing versus office testing, that will provide community members an opportunity to participate in the research. 

Impact Lives Here

The University of Cincinnati is leading public urban universities into a new era of innovation and impact. Our faculty, staff and students are saving lives, changing outcomes and bending the future in our city's direction.  Next Lives Here.

Featured photo at top of HPV test form. Photo/iStock/Sefa Ozel.

• Clinical Research
• Faculty Staff
• Obstetrics & Gynecology
• College of Medicine
• Academic Health Center
• UC Cancer Institute

Related Stories

April 11, 2024

The University of Cincinnati Cancer Center is one of 25 sites across the country hosting the SHIP trial testing whether samples self-collected by patients for HPV testing are as accurate and effective as clinic-collected samples.

UC cancer research presented at national meeting

May 26, 2023

University of Cincinnati Cancer Center researchers will present abstracts at the American Society of Clinical Oncology (ASCO) annual meeting 2023, held in Chicago June 2-6.

OncLive and Targeted Oncology: Drug yields long-lasting benefits to treat PEComa tumors

March 22, 2024

OncLive and Targeted Oncology covered research presented by the University of Cincinnati's Thomas Herzog that found patients with perivascular epithelioid sarcoma (PEComa) of gynecologic or peritoneal origin experienced rapid, durable responses when treated with the drug nab-sirolimus.

An official website of the United States government

The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• Browse Titles

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Cervical cancer.

Josephine R. Fowler ; Elizabeth V. Maani ; Charles J. Dunton ; David P. Gasalberti ; Brian W. Jack .

Affiliations

Last Update: November 12, 2023 .

• Continuing Education Activity

Cervical cancer, the fourth most common cancer among women worldwide, is caused almost entirely by human papillomavirus (HPV). High-risk types of HPV can lead to cervical intraepithelial lesions which, over time, can progress to cervical cancer. In the United States and other developed countries, most screening and early detection efforts involve HPV testing and Papanicolaou (Pap) smears. HPV testing identifies exposure to both low- and high-risk types of HPV, whereas Pap smears identify abnormal cytology.

Cervical cancer is a largely preventable disease. Primary prevention and screening are the most effective modalities for decreasing the healthcare burden and mortality attributable to cervical cancer. Since 2006, HPV vaccination has been available to prevent cervical cancer. Interprofessional team members must educate young female patients (ideally, prior to initiating sexual activity) and their families about this highly effective vaccine. This activity details primary prevention strategies, screening guidelines, diagnostic evaluations, current staging, and specific treatment modalities for invasive cervical cancer.

• Identify the risk factors, signs, and symptoms of cervical cancer, including the role of high-risk HPV types in its development.
• Apply evidence-based treatment modalities for precancerous cervical lesions, and assess the indications, techniques, potential complications, and follow-up care associated with these interventions.
• Select appropriate treatment modalities for invasive cervical cancer based on patient characteristics, staging, and available options, including surgery, radiation, and chemotherapy.
• Collaborate with the interprofessional team to increase HPV vaccination initiatives and to ensure coordinated and comprehensive care for patients diagnosed with cervical cancer.
• Introduction

Cervical cancer continues to rank among the top gynecologic cancers worldwide. According to current data, it is ranked 14th among all cancers and is the 4th most common cancer among women worldwide. [1] Cervical cancer intervention focuses on primary and secondary prevention. [2] Primary prevention and screening are the best methods to decrease the burden of cervical cancer and mortality.

In the United States and other developed countries, most screening and diagnostic efforts are directed toward the early identification of high-risk human papillomavirus (HPV) lesions through HPV testing and Papanicolaou (Pap) smears. Although HPV testing is not recommended in women younger than 30 years, low-risk younger women should begin screening with Pap tests at age 21 and continue until age 65, per the United States Preventive Services Task Force (USPSTF) recommendations. Newer recommendations offer 3- to 5-year intervals between screenings based on a patient's prior results and the use of Pap and HPV cotesting. [3] [4]  

Like many diseases and cancers, disparities exist in screening, early diagnosis, and timely treatment rates. Screening rates are lower in low socioeconomic and low-resource areas with racial, ethnic, and age variations. Studies show women with obesity and chronic disease may have lower cervical and breast cancer screening rates. A study of ethnic minority women in the United Kingdom reports several barriers to screening, including lack of awareness, fear, embarrassment, shame, and low perceived risk. [5]  Another study reviewing the barriers for Haitian women revealed socioeconomic barriers, language barriers, and a limited understanding of health and disease. [6]  In the United States, cervical cancer mortality is disproportionately higher in black women.

As cervical cancer is a sexually transmitted infection (STI), it is preventable, and the global incidence can be reduced through targeted education, screening, and intervention. Since 2006, vaccination has been available for the prevention of cervical cancer. Vaccination can improve cancer death rates in populations with higher mortality rates and in developing countries where resources may not be available for routine screening. 

Current literature reports that HPV is found in most sexually active people at some point during their lifetime. There are more than 130 types of known HPV, with 20 HPV types identified as cancer-related. HPV exposure rates are only known in women since men are not screened outside of research protocols. HPV types 16 and 18 are the most common HPV types identified in invasive cervical cancer. Population-based HPV prevalence studies show the greatest prevalence of high-risk HPV occurs in adults younger than 25 years, and cervical cancer deaths peak in middle-aged women between 40 and 50 years. Studies have shown that HPV-related cervical disease in women younger than 25 years is largely self-limiting. However, those with coinfection of multiple HPV types may be less likely to have spontaneous clearance and, thus, progress to cancer.

HPV is transmitted by skin-to-skin contact, including during sexual intercourse, hand-to-genital contact, and oral sex. Risk factors for HPV and cervical cancer include young age at sexual initiation, multiple sexual partners, high parity, smoking, herpes simplex, HIV, coinfection with other genital infections, and oral contraceptive use. [7] [8]

• Epidemiology

Persistent HPV infection causes more than 99% of all cervical cancers. Every year, there are more than 500,000 new cases of cervical cancer and approximately 250,000 deaths due to cervical cancer worldwide. Eighty percent of cases occur in developing countries. [9] In the United States, about 4000 women die yearly from cervical cancer. Blacks, Hispanics, and women in low-resource areas have more disparity in evidenced-based care and a significantly higher mortality rate. [10] [11]  Mortality is higher among women not screened in the past 5 years and those without consistent follow-up after identifying a precancerous cervical lesion. Trends show that women with the highest-mortality risk may be less likely to receive HPV vaccination.

• Pathophysiology

More than 75% of cervical cancer cases are due to high-risk HPV types 16 and 18. [12] Other HPV types also can cause malignancy. Some low-risk HPV types, specifically types 6 and 11, cause condylomata acuminate, commonly referred to as anogenital warts. Although there are more than half a million cases of HPV identified annually, most are low-grade infections and will spontaneously resolve within 2 years. The progression of high-grade lesions and cancer is seen in the presence of other carcinogenic risk factors, as previously described.

Within HPV DNA, the oncoproteins E6 and E7 interfere with the critical host cell cycle; specifically, E6 interferes with suppressive tumor protein p53, whereas E7 interferes with retinoblastoma protein (pRB). Additionally, the E5 protein may play a role in immune evasion. These are significant factors in HPV-related neoplasia, including primary vagina cancer. [13]  Oxidative stress and microRNAs are believed to play a role in cervical carcinogenesis. Future research to elucidate the proposed interplay is needed. [12] [14]

• Histopathology

Squamous cell carcinoma and adenocarcinoma are the most common histological subtypes of cervical cancer, with squamous cell carcinoma being vastly more frequent. Adenocarcinoma constitutes approximately 5% of invasive cervical cancers worldwide, although this percentage is increasing in some countries. [15]   Both subtypes result from precursor lesions, cervical intraepithelial neoplasia (CIN), or carcinoma in situ (CIS). Squamous CIS and adenocarcinoma in situ (AIS) are the most immediate precursors to invasive cervical cancer. Adenocarcinoma of the cervix should be carefully distinguished from endometrial adenocarcinoma with immunohistochemistry and HPV in situ hybridization. [16]   

Most malignancies arise from the sqamocolumnar junction of the cervix. Microscopically, anastomosing irregular nests or single tumor cells with stromal inflammation or desmoplasia are present. Lymphovascular invasion (LVI) may also be present. Grading is predicated on nuclear pleomorphism, nucleoli size, mitotic activity, and necrosis, and does not correlate with prognosis. [17]

• History and Physical

Patients with cervical cancer are usually asymptomatic during the early stages. A complete medical history must include a sexual history, including the patient's age at first sexual encounter. Sexual history also includes questions about postcoital bleeding and pain during intercourse. Questions about previous STIs, including HPV and HIV, the number of lifetime sexual partners, tobacco use, and prior vaccination against HPV are all vitally important. [18] Women should also be asked about menstrual patterns, abnormal bleeding, persistent vaginal discharges, irritations, and known cervical lesions. [19]

The physical exam must include a complete evaluation of the external and internal genitalia. Positive exam findings in women with cervical cancer might include a friable cervix, visible cervical lesions, erosions, masses, bleeding with the examination, and fixed adnexa. [20]  Many patients will have no positive findings on physical examination. Screening by Pap and/or HPV testing is essential in the workup and diagnosis of patients with cervical cancer and its precursor lesions.

According to the United States Preventative Services Task Force (USPTF), Pap screening is recommended beginning at age 21; at age 30, HPV testing starts in conjunction with Pap smear cytology. Screening is recommended every 3 years for women with continued negative screening results and those at low risk for cervical cancer. For women older than 30 years, cytology can be done every 5 years with HPV testing. One Level A recommendation for women with low-risk status and consistently negative screenings is discontinuing cervical cytology and HPV testing at age 65. Women who have had a total abdominal hysterectomy, including removal of the cervix for benign disease, do not require subsequent screening. [4]

Colposcopy is the diagnostic procedure of choice for evaluating abnormal cytology and/or persistent high-risk HPV infection. The American Society for Colposcopy and Cervical Pathology (ASCCP) has issued guidance on procedural indications, and their recommended algorithms are considered standard of care. Multiple colposcopic-guided biopsies and endocervical sampling are often indicated, except during pregnancy. [21]  Abnormal colposcopic findings may include acetowhite color change with the application of acetic acid, rich vascularity, atypical vessels, mosaicism, and punctation (see Image.  Invasive Cervical Cancer).

Patients diagnosed with invasive disease require a comprehensive staging workup. The International Federation of Gynecology and Obstetrics (FIGO) staging system employs several methods to stage a patient's disease. Classically, staging was based on the local extent of the tumor, which could be determined with a combination of pelvic examination, cystoscopy, proctoscopy, chest x-ray, intravenous pyrography, and basic labs. More recently, advanced imaging modalities such as MRI and PET scans have been utilized for staging. A pelvic MRI is excellent for detecting local tumor extension and can also be used for monitoring tumor response. PET scans are more sensitive than CT scans for detecting nodal and visceral metastases. This is critical as nodal disease can significantly influence prognosis. [22]

• Treatment / Management

Precancerous lesions are managed conservatively for women younger than 25 years. Most positive findings in women younger than 25 years are low-risk cervical dysplasia and will resolve spontaneously. Colposcopy evaluates persistent, abnormal cytology or lesions suspected to be moderate or high risk. These are managed according to findings.

Low-risk lesions may be observed and reevaluated more frequently, and high-risk lesions are treated based on size, depth, and location. Cryotherapy or excision is performed to manage precancerous lesions limited in size and depth. Conization, laser, or loop electrosurgical excision procedure (LEEP) are used to manage lesions that include the endocervical canal and are more extensive. LEEP may provide better visualization of the squamocolumnar junction and provide the benefit of less bleeding in the outpatient setting. [23]

If invasive cancer is diagnosed, the next step in management is staging to determine further treatment. Staging is based on findings and results from reported signs and symptoms, examination, tissue pathology, and imaging. Grading is based on the size and depth of the cancer and signs of spread to other organs. Treatment of early-stage disease is typically surgical resection, ranging from a conization to a modified radical hysterectomy. However, women with high-risk pathology postresection may require adjuvant treatment with chemotherapy and radiation. Conization or trachelectomy may be an option for women with early-stage disease who desire future fertility. For patients with more advanced disease, concurrent chemoradiation is the standard of care.

• Differential Diagnosis

Evaluating visible cervical lesions for invasive cancer is essential. However, as discussed above, most cervical cancer is asymptomatic and will not present with an overt mass in the early stages. Other possible causes of cervical lesions and/or abnormal bleeding include STIs, cervical polyps or fibroids, and endometriosis. Diagnosis may require further evaluation of symptoms and testing to determine whether the disease is cervical cancer. A diagnostic biopsy is needed to finalize the diagnosis.

Other pathology-determined conditions in the differential diagnosis include carcinosarcoma, epithelioid trophoblastic tumor, placental site nodule, immature squamous metaplasia, and metastatic disease from a noncervical primary tumor. Rarely, a routine Pap smear may identify metastatic cancer on the uterine cervix. [24]

• Surgical Oncology

Surgical resection is offered to patients with early-stage disease confined to the cervix; it can range from relatively noninvasive procedures such as cervical conization to more extensive operations such as radical hysterectomy. Although surgery is the preferred treatment modality for early-stage cervical cancer, it is especially important in younger patients for whom preservation of ovarian function and/or fertility is desired. Surgery is also indicated in select patients with recurrent disease.

Types of Surgery

Cervical conization

Cervical conization is typically indicated in patients with CIS or stage IA1 invasive cervical cancer. Using a scalpel or laser, a cold knife cone (CKC) removes the cervical transformation zone and a portion of the cervix with at least a 3-mm margin. Pathologic evaluation of the margins and assessment of the presence or absence of lymphovascular invasion (LVI) are critical. If a positive margin or LVI is present, reexcision or more invasive surgical treatment may be required.

If no LVI exists on the specimen, lymph node involvement is exceedingly rare, so nodal evaluation is unnecessary. Patients without any adverse pathologic findings may be observed. Recurrence rates are typically <10%, but patients must be followed closely with periodic colposcopy and cytology. Five-year survival rates exceed 95%. Complications include hemorrhage, infection, cervical incompetence, cervical stenosis, and infertility. The complication rate ranges from 2% to 12%. [25] [26]

Radical trachelectomy

Patients who are not candidates for conization due to adverse pathological features or more advanced disease but who desire future fertility are candidates for a radical trachelectomy. The procedure consists of removing most of the cervix, resecting the parametria, and mobilizing the ureters, bladder, and rectum. A 5-mm section of the cervix is preserved for the placement of a cerclage, allowing for future pregnancy. Due to the increased risk of nodal involvement, a lymph node evaluation with a sentinel node biopsy or pelvic lymphadenectomy typically accompanies a radical trachelectomy.

Adverse pathologic features such as positive margins, parametria involvement, lymph node involvement, or meeting Sedlis criteria would necessitate adjuvant treatment with radiotherapy with or without chemotherapy. A vaginal approach or laparotomy can be used, but there are insufficient data on minimally invasive techniques. The 5-year recurrence rate is approximately 5%, and the overall survival rate is 97%. The pregnancy rate postprocedure is 24%, with a live birth occurring in 75% of patients. [27] Complications include cervical suture problems, dysmenorrhea, isthmic stenosis, and vaginal discharge.

Extrafascial hysterectomy

Extrafascial hysterectomy, also known as a Type A radical hysterectomy, has a narrow range of clinical indications. [28] Typically, this surgery is offered to patients with stage IA1 disease who are not interested in future fertility; it involves the removal of the entire cervix and uterus. As ovarian removal is optional, ovarian function can be preserved. The parametria are not resected, and a vaginal approach or laparotomy may be utilized. Lymph node evaluations are not usually performed unless adverse pathologic features are discovered postoperatively. Patients with adverse pathologic features may require a complete parametrectomy or external beam radiotherapy with or without chemotherapy.

Radical hysterectomy

A radical hysterectomy may be considered in almost all early-stage cervical cancer cases when fertility preservation is not desired. The older Piver-Rutledge-Smith classification has been replaced by the Querleu–Morrow system, which simplifies the classification process based solely on the extent of lateral parametria resection. Four types of radical hysterectomy are described (Types A through D). Type A includes a minimal parametrial resection. In contrast, Type D completely resects the paracervical region to the pelvic sidewall. The most commonly performed radical hysterectomies fall in the Type B and C categories, which differ in the transection of the paracervical region at the level of the ureters or internal iliac vessels, respectively. [29]

Minimally invasive approaches have been shown to provide inferior oncologic outcomes compared with more established open approaches in terms of disease-free survival (91% vs 97%) and overall survival (93% vs 99%), with most patients having stage IB1 disease. [30]  Complications include bleeding, infection, venous thromboembolism, pulmonary embolus, small bowel obstruction, vesicovaginal fistula, hydronephrosis, ureteral injury, urinary stress incontinence, and lower extremity edema.

Laparoscopic radical hysterectomy

Although this procedure offers a quicker recovery for the patient, it has been largely abandoned due to poor oncologic outcomes and increased recurrence compared with open surgery. The mechanism for this difference is unknown, but 2 large independent studies have confirmed this finding. [31] [32] [33]

Lymph node evaluation

Detecting lymph node involvement is essential, as it yields important prognostic information and guides therapeutic decision-making. The risk of nodal involvement should guide the decision to evaluate the lymph nodes and is a function of the disease stage (see Table.  Pelvic Nodal Risk by Stage). Para-aortic (PA) nodal risk typically carries one-half the pelvic nodal risk by stage. Although pelvic lymphadenectomies are considered the gold standard, sentinel node biopsies may also be pursued for select early stage I cervical cancer. Generally, sentinel node biopsies are safe and effective. They have been investigated in stage IA1 to stage IIA1 patients with a sensitivity of 92%, a negative predictive value of 98%, less lymphatic morbidity, and no differences in recurrence-free survival. [34] [35] The sentinel node biopsy approach continues to be investigated in large-scale international trials called SENTICOL III ( NCT03386734 ).

Table.  Pelvic Nodal Risk by Stage

Pelvic exenteration

Pelvic exenteration is the most radical surgical procedure for cervical cancer. Indications are confined to patients with central pelvic recurrence after radiotherapy or patients with stage IVA disease who cannot receive radiotherapy. Classically, a total pelvic exenteration includes the removal of the uterus, fallopian tubes, ovaries, vagina, bladder, urethra, and rectum. Reconstruction consists of an ileal conduit, or continent diversion, for the urinary system and an end colostomy for the GI system. Continent diversions include the Indiana and Miami pouch techniques. [36] [37]  

Total exenteration is generally performed for cervical cancer. Variations of this technique include anterior and posterior exenteration, which spare the rectum or the bladder, respectively. Exenteration can be further classified into supralevator and infralevator, depending on whether the urogenital diaphragm and levator muscles are removed. It is important to ensure that the central tumor can be completely resected and there is no metastatic disease. Minimally invasive pelvic exenteration has been described in the literature, although further evaluation of this technique is warranted. [38] [39]  

A neovagina can be formed with a myocutaneuous flap or split-thickness skin graft with an omental J-flap. The posterior supralevator exenteration approach allows for the possibility of maintaining not only urinary function but fecal continence if a colonic anastomosis can be formed. The 5-year survival rate for patients treated with exenteration ranges from 40% to 50% in the recurrent setting. [40]  At 3 and 5 years, local recurrence rates are 84% and 75%, respectively. [41] Survival is not impacted by the type of exenteration performed. [42] Mortality from the operation has fallen dramatically over the last 70 years to less than 5%, but surgical morbidity is over 50%. [41] Early complications include infection, abscess formation, thromboembolism, fistulas, urinary leakage, peritonitis, stoma necrosis, flap necrosis, and stump dehiscence. Late complications include stoma stenosis, incontinence, hydronephrosis, stone formation, chronic pain, and abdominal wall hernia.

Cervical Cancer in Pregnancy

Although cervical cancer is one of the most common malignancies diagnosed in pregnancy, it poses unique staging and treatment challenges in pregnant patients. A maternal-fetal medicine specialist should evaluate patients to discuss fetal risks and potential pregnancy loss. Women must weigh the risk of delaying treatment until after delivery versus proceeding immediately with treatment.

The determination of gestational age is crucial. Minimum fetal viability is approximately 24 weeks gestation, but there is a significant risk of neonatal death or long-term disability in those who survive. Disability-free survival at 25 years increases substantially with advancing gestational age, with 4% of infants born at 22 weeks versus 78% for those born at 28 weeks gestation. In contrast, full-term infants have a disability-free survival of 97%. [43]

While the radiation delivered during a PET or CT scan remains far below the threshold for the development of congenital malformations and pregnancy loss, ionizing radiation in imaging studies should be kept to a minimum in this population. [44] Other imaging modalities, such as ultrasound and MRI, are preferred when appropriate to determine local tumor extent and distant metastatic involvement. However, MRI and ultrasound have a low sensitivity for small nodal metastases. Consequently, more invasive staging techniques may need to be employed.

In patients with a high risk of nodal metastasis, laparoscopic pelvic lymphadenectomy may be performed to establish the disease stage. [45]  The safety of this procedure has only been studied in limited case series, but it can be performed in any trimester (although earlier in the pregnancy is preferred). These techniques may still be employed when advanced imaging is unavailable or contraindicated. In addition, the FIGO staging system continues to allow the use of proctosigmoidoscopy and cystoscopy for local staging of cervical cancer.

Treatment strategies must be individualized and discussed in a multidisciplinary fashion with medical oncologists, radiation oncologists, obstetrician/gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. Generally, patients with pregnancies at gestational ages under 22 weeks and stage IA1 disease can be treated with conization, but this carries a 15% risk of significant bleeding and spontaneous abortion. Patients with pregnancies at gestational ages above 22 weeks may be able to delay treatment until after delivery if they have early-stage disease. Patients with more advanced disease (>IB1) may receive platinum-based neoadjuvant chemotherapy (cisplatin/paclitaxel) until delivery, followed by a cesarean radical hysterectomy. Limited data suggest this is a safe regimen for both mother and fetus. [46]  Small series indicate approximately a 75% tumor response rate, with 15% of patients experiencing a local recurrence. The risk of fetal toxicity with these regimens is unknown, but complications may include respiratory distress syndrome, malformations, and childhood malignancies. [46]    International guidelines for treatment and fetal preservation have been published. [47]

Immediate treatment is recommended for patients with documented lymph node metastasis, disease progression, or pregnancy termination. If the patient opts to terminate the pregnancy before treatment, definitive treatment recommendations are identical to those of a nonpregnant patient.

• Radiation Oncology

Radiotherapy remains a crucial component in the treatment of cervical cancer. Randomized evidence from the 1990s and early 2000s has established radiotherapy in almost every facet of treatment; it may be utilized as a definitive or adjuvant treatment with or without platinum-based chemotherapy.

Definitive Radiotherapy

Early-stage cervical cancer

Radiotherapy may be utilized as the sole treatment modality in early-stage cervical cancer (stages IA1 to IIA1). External beam radiotherapy (EBRT) with a brachytherapy (BT) boost has less morbidity and equivalent 5- and 20-year overall survival rates (83% and 75%, respectively) compared with radical hysterectomy. [48] [49] Some centers may perform an adjuvant hysterectomy for bulky tumors after chemoradiation therapy. However, most guidelines do not recommend this due to significant complication rates. Recent data suggest that survival rates after chemoradiation therapy and adjuvant hysterectomy are suboptimal. [50]

Advanced cervical cancer

Locally aggressive and/or node-positive diseases are typically treated with definitive concurrent platinum-based chemoradiotherapy followed by a BT boost. The addition of chemotherapy to definitive radiotherapy has resulted in considerable improvement in overall survival compared with radiotherapy alone, with an 8-year overall survival of 67% versus 41%. Improvements in local recurrence and distant metastasis have also been noted. [51]

Postoperative radiotherapy

Radiotherapy with or without chemotherapy is recommended in the postoperative setting when specific pathologic findings are present. These findings are thought to represent an increased risk of recurrence.

Conventionally, the Sedlis criteria guided the use of adjuvant radiotherapy without chemotherapy in postradical hysterectomy patients with at least 2 of the following 3 features: tumor size greater than 4 cm, LVI, or more than one-third stromal invasion. [52] These criteria were meant to identify patients with at least a 30% risk of relapse at 3 years. [53] Patients who met these criteria and were treated with pelvic radiotherapy were noted to have improved progression-free survival (78% vs 65%) and local recurrence (21% vs 14%). [52] More recently, there have been concerns that these criteria may overlook women who might benefit from adjuvant radiotherapy due to such a high threshold. A nomogram incorporating the original Sedlis criteria and tumor histology has been developed to provide a more linear and continuous risk assessment rather than a simple threshold. [53]

Classically, the addition of chemotherapy to radiotherapy was guided by the Peters trial, which randomized patients with positive nodes, involved parametria, or positive surgical margins to radiotherapy alone or radiotherapy with concurrent platinum-based chemotherapy. The addition of chemotherapy resulted in a 10% improvement in overall survival at 4 years and almost a 20% improvement in progression-free survival over the same time frame. [54] More contemporary studies such as the STARS trial have sought to expand the use of chemotherapy in the adjuvant setting in patients meeting either the original Sedlis or Peters criteria. [55]

Delivery Techniques

The 2 major delivery methods include ERBT, directed at the primary tumor and pelvic lymphatics, and BT, in which a sealed radiation source is placed in close proximity to the tumor. 

EBRT techniques include 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). Intact cervical cancer patients’ plans can be employed. A reduction in gastrointestinal and hematological adverse effects has been documented with IMRT in both adjuvant and definitive settings. [56] [57]

ERBT simulation

Patients undergoing EBRT can be placed in the supine position. Accounting for cervical motion is essential when using IMRT. This is accomplished by taking 2 separate scans of patients, first with a full bladder followed by an empty bladder. Prone positioning may also be accomplished using a belly board; however, if there are large daily fraction shifts, IMRT may not be reproducible. Prone positioning may allow for a reduction in the small bowel dose when using IMRT. [58]

ERBT target delineation

Traditionally, pelvic fields were drawn on 2-D x-rays consisting of anterior-posterior (AP)/posterior-anterior (PA) and opposed lateral fields comprising the 4-field box. The superior edge of the field was the bottom of L4 and inferiorly drawn to the bottom of the obturator foramen (or at least 3 cm below the lowest extent of disease). The lateral fields have the same superior/inferior borders, with the anterior border being the anterior pubic symphysis and the posterior border being the sacral hollow, including S2.

More precise delineation of the gross disease and elective volumes can be accomplished in the era of CT-based planning, PET/CT fusions, and IMRT. A gross tumor volume (GTV) consists of gross disease seen on a CT, PET, and physical examination. An internal target volume (ITV) accounts for variation in bladder filling and can also be employed, but this requires the patient to have 2 CT simulations (empty and full bladder). The clinical tumor volume (CTV) 1 expansion includes the entire cervix and uterus (if intact). Planning target volume (PTV) 1 on primary disease is typically 1.5 cm. The CTV2 includes the parametrial tissue, paravaginal tissues, and at least one-half of the upper vagina. If there is vaginal involvement, consideration should be given to covering the entire vagina. This PTV2 expansion should be 1.0 cm. The elective nodal volumes in the CTV3 should include obturator nodes, external iliac nodes, internal iliac nodes, and presacral nodes. If there is lower vaginal involvement, consideration should be given to coverage of the inguinal nodes. PTV expansion on the elective nodes is typically 0.7 cm.

Coverage of the PA nodes may be necessary in cases with evidence of disease in the nodal chain, or in cases in which the patient has a positive pelvic node and will not receive systemic therapy. In those instances, the superior boundary would become the T12/L1 interspace, with the nodal strip ending at the top of the pelvic field L5/S1. [59] [60]

ERBT dosing and dose constraints

The standard whole pelvic dose is 45 to 50.4 Gy, specifically 1.8 to 2.0 Gy per fraction. Any gross nodal disease may be boosted to 60 Gy if possible, given that organs-at-risk (OAR) constraints are not exceeded.

EBRT has dramatically improved with the adoption of IMRT, reducing acute toxicity while maintaining oncologic outcomes. Typical OAR include the rectum, bladder, bowel, femoral heads, and bone marrow. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC)   dose constraints can be an excellent guide. Typically, with EBRT, doses of 45 to 50 Gy alone will not lead to significant rates of acute bladder or bowel toxicity. [57]

If BT is planned, minimizing these doses during the external beam phase of treatment will allow higher doses to be delivered during the boost phase of treatment. Bone marrow suppression resulting in grades 3 to 4 neutropenia has been demonstrably lower (8.6% vs 27.1%) with image-guided radiotherapy and IMRT. [56] The most common constraints are for bone marrow in the pelvis. [56] [57] [61]

BT can be used alone in early-stage cervical cancer or as a boost after EBRT in more advanced disease (stages IB2 to IVA), as it allows for highly conformal dose delivery to the tumor while minimizing exposure to normal tissues. The dose delivery is controlled by adjusting the dwell times within the delivery device. High dose-rate (HDR) BT (>12 Gy/hr) is the most commonly used technique; however, it requires a radioactive source, usually iridium-192.

Typically, BT is started after the external beam portion of the treatment or interdigitated with EBRT in the last week of treatment. EBRT and BT should not be administered on the same day. Total treatment time (EBRT and BT) should not exceed 8 weeks. Excessive treatment times can result in a 1% per day decline in local control and overall survival.

Before undergoing BT, a review of the patient’s history, physical exam, pathology, and imaging should be conducted. A complete blood count and metabolic panel should be obtained within a week of the procedure. Metabolic derangements should be investigated and corrected before the procedure. Patients with an absolute neutrophil count (ANC) less than 500 mm should not undergo the procedure until their count has recovered. A review of medications, especially anticoagulants, should be completed, and a prothrombin time/international normalized ratio result should be obtained. Careful consideration should be given to holding anticoagulant medications before the procedure. Inpatients confined to bed should be given thromboprophylaxis and sequential compression devices. Bowel preparation should also be reviewed with the patient before the procedure.

BT applicators

There are several applicators that may be used in various clinical scenarios. The ring and tandem is the most common device for intact cervical cancer. The tandem is placed in the cervical canal while the ring is placed inside the vaginal fornices. Tandem and ovoids are utilized similarly but are preferred in patients with a barrel-shaped cervix. Interstitial applicators such as the Syed template can be used in patients with extensive parametria involvement, pelvic sidewall involvement, lower vaginal involvement, or vaginal cuff recurrence. Tandem and cylinder applicators can be used in cases of vaginal stenosis, inability to place a ring or ovoid, or lower vaginal involvement less than 5 mm thick. Modifications to the tandem and ring or vaginal cylinder can also be made to accommodate interstitial needles. [62] [63]

Patient discomfort experienced during the procedure can lead to suboptimal placement of the applicator, longer procedure times, and distress for the patient. An anesthetic is typically required to help optimize patient comfort and procedure mechanics. The types of anesthesia administered vary but may include general anesthesia, spinal anesthesia, epidural anesthesia, intravenous conscious sedation, and oral pain medication.

Placement of an intracavitary applicator for an intact cervix

The patient is placed in the dorsal lithotomy position in stirrups. After adequate sterile preparation of the area, a Foley catheter is inserted, and the balloon is inflated with dilute contrast to allow for detection with CT scan. A speculum is inserted to visualize the cervix, and a uterine sound is used to determine the length of the cavity. This will aid in determining the length and angle of the tandem. A Smit sleeve is occasionally used to maintain the patency of the cervical os but, if not available, serial dilations may be required. Once this is complete, the tandem is inserted, followed by the ring or ovoid. Fiducial markers may also be placed during the procedure to outline the extent of the disease or the opening of the cervical os so it is visible on CT scan. These applicators can be locked so their relative positions do not change.

Displacement of the bladder and rectum is critical to reduce the excess dose and limit toxicity. The packing material can consist of gauze soaked in a radiopaque solution. Applicators fitted with inflatable balloons or separate rectal blades are also available. Anterior packing displaces the bladder, whereas posterior packing displaces the rectum. It is essential to ensure no packing is placed in front of the ring or ovoids, as this will significantly reduce the intended dose.

Once complete, the patient will undergo a CT simulation for 3-D BT planning. Three-dimensional CT-based planning has been shown to have improved overall survival (65% vs 74%) and lower rates of grades 3 to 4 toxicity (23% vs 3%) compared with 2-D planning. [64]   A 1- to 5-mm slice thickness is recommended. [62] [63] More recently, MRI-guided BT has been incorporated into planning for improved tissue delineation, best seen on the T2-weighted fat-suppressed sequences (T2–fast-spin echo) imaging. [65]

Paraxial and para-coronal images should be obtained concerning the cervix-uteri and sagittal images. [66]  These images can also allow for the assessment of chemoradiation response.   Technically, low- and high-intensity magnetic field MRI machines can be used. Patients can be given glucagon before MRI to reduce bowel motion. A pelvic coil is recommended to increase the signal-to-noise ratio. Ideally, a 3-mm slice thickness should be obtained, which helps improve the detection of parametrial involvement, but a slice thickness of less than 5mm is acceptable. The disadvantages of this approach are the increased costs, longer procedure times, and the need for strict compatibility of the materials utilized.

Proper applicator placement should be confirmed with plain radiography or more advanced imaging such as a CT scan or MRI. Adequate placement includes the tandem bisecting the ring/ovoids on AP and lateral imaging, the tandem being one-third to one-half the distance between the sacral promontory and the pubic symphysis, the tip of the tandem being below the sacral promontory, no packing located superior to the ring/ovoids, and no inferior displacement of the ring/ovoids relative to the flange. 

With HDR BT, a remote afterloading technology allows a small iridium source attached to the end of a cable to be robotically driven through multiple channels, stopping at predetermined points (dwell positions) for varying lengths of time. [67]  A Cochrane review failed to show differences between HDR and low dose-rate (LDR) intracavitary brachytherapy (ICBT). Oncologic outcomes included overall survival, disease-free survival, and recurrence-free survival, as well as local control rate, recurrence, and metastasis. There was no difference in treatment-related complications. Regardless, this review recommends HDR ICBT for all clinical stages of cervix cancer due to the advantages of HDR ICBT, including accuracy of the source, applicator positioning, outpatient treatment, and patient convenience. [68]

BT target delineation

As part of 3-D–based planning, contouring the targets is essential. The Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) have established standardized terminology regarding target delineation. [66] The high-risk clinical target volume (HR-CTV) consists of the entire cervix and all gross disease at the beginning of BT treatment; the intermediate-risk clinical target volume (IR-CTV) incorporates the HR-CTV and gross disease before any treatment; and the low-risk clinical target volume (LR-CTV), which includes the IR-CTV as well as the entire uterus, upper vagina, entire parametria, and spaces between the bladder and rectum. [69]  Normal OAR should be contoured, including the bladder, rectum, sigmoid colon, and vagina.

BT dose and dose constraints

Ensuring adequate dose to the target is critical and has been shown to lead to improved local control and survival. Dose and fractionation schemes may vary by institutional preference, but they must result in a total equivalent dose in 2 Gy fractions (EQD2) of 85 Gy or higher, assuming 45 Gy was initially delivered to the pelvis. There are several calculators to determine EQD2. One of these, colloquially known as the “Vienna Spreadsheet,” was used by the Effects of a Multifaceted Intervention on Blood Pressure Actions in the Primary Care Environment (EMBRACE) trial group; it provides EQD2 calculations to the target structures and OAR. The most common dose fractionation schemes include 4 x 7 Gy, 5 x 6 Gy, and 6 x 5 Gy, with an EQD2 of approximately 90.1, 88.6, and 83.7 Gy, respectively.

For 3D-based planning, the critical dosimetric parameter is the D90 greater than or equal to 90%. The goal is for 90% of the HR-CTV to be covered by at least 90% of the prescription dose. The EQD2 should be calculated to ensure the total dose received is approximately 85 Gy or higher, although there are instances in which it is acceptable for the EQD2 to be slightly lower. In patients with a complete response before BT or partial response with less than 4 cm in residual disease, an EQD2 above 80 Gy may be used, whereas for those patients with more than 4 cm residual disease, an EQD2 greater than 85 Gy is recommended. [62] [63]

Despite the transition to 3D-based volumetric planning and the continued evolution of BT treatment, 2-D dosimetric reporting systems persist and should be understood. Point A, where the uterine artery crosses the ureter, is located 2 cm up the tandem and 2 cm lateral to the tandem and was originally part of the Manchester system. This point was traditionally where the prescription dose was prescribed, but more recently has become a starting point where dose coverage can be further manipulated in 3-D to ensure coverage of the HR-CTV. Point B, also part of the original Manchester system, is located 2 cm up the tandem and 5 cm from the patient’s midline. This location represents the pelvic side wall lymphatics and typically receives one-third of the prescription dose. It has fallen out of favor and is no longer reported. The isodose lines for typical tandem and ring/ovoid implant should appear pear-shaped. In addition, the International Commission on Radiation Units and Measurements (ICRU 38) specified a bladder and rectal point. The bladder point is located posterior to the Foley balloon that has been pulled down to the neck of the bladder. The rectal point is 5 mm posterior to the vaginal wall.

Doses to OAR must also be carefully documented. Again, it is the cumulative dose of EQD2 that is critical. The dosimetric parameter D2 cc, which represents the highest dose received by 2 ccs of tissue, is commonly used for evaluating a BT plan. The American Brachytherapy Society (ABS) guidelines allow for the D2 cc of the bladder to receive 90 Gy or less EQD2, whereas the D2 cc of the rectum and sigmoid should be 75 Gy or less EQD2. However, recent data suggest that late rectal morbidity may be substantially lower even using a D2 cc of 65 Gy or less. [70]

Radiation Therapy Complications

Long-term toxicity is a concern with any patient receiving radiation therapy. Bowel, rectal, and urinary complications are the most frequent. There does not appear to be a difference in the frequency or severity of complications with respect to age. The greatest risk of late sequelae typically occurs within 3 years of treatment.

Radiation proctitis can result in tenesmus and intermittent bleeding with bowel movements. Postradiation proctitis typically occurs 3 months after treatment at the earliest but may take years to develop. Treatments can include mesalamine or steroid-based suppositories to relieve pain and stop bleeding. Randomized trials have suggested that mesalamine may be slightly more efficacious than steroid-based suppositories. [71]  Other treatments can include a 4% formaldehyde application to control rectal bleeding. In refractory cases, argon plasma laser coagulation may be performed on the offending vessels.

Radiation cystitis can lead to dysuria, urinary frequency, and, in some cases, hematuria. This complication can occur acutely within 2 to 3 weeks of starting radiotherapy and up to 3 years posttreatment.

For acute cystitis, a urinary tract infection must be ruled out; therefore, a urinalysis is an appropriate first step in the diagnosis. A short course of phenazopyridine can be prescribed for dysuria relief, although the urine color change may be alarming for some patients. Patients should be made aware of this change before starting the medication. Urinary frequency can be treated with anticholinergic drugs such as oxybutynin or mirabegron, although caution is advised in elderly patients.

Chronic cystitis has an incidence of 5% to 10%. [72] These patients are more likely to experience hematuria in addition to frequency and dysuria. The severity can range from mild to severe and life-threatening. Mildly symptomatic patients may be managed conservatively. Any antiplatelet or anticoagulation medications the patient takes should be reviewed, and the necessity questioned. A cystoscopy with clot evacuation and irrigation is necessary in more severe cases. During a cystoscopy, formalin instillation can be used to manage intractable hematuria. In refractory cases, hyperbaric oxygen therapy has been utilized and shown to relieve and control bleeding in 92% of patients; however, recurrences may occur. [73]  Barotrauma is a risk associated with this procedure.

Secondary malignancy

Radiation-induced cancers tend to appear several decades after treatment. The overall risk of secondary malignancy is increased with pelvic radiotherapy compared to those treated with surgery alone. Women younger than 50 years had a 40-year cumulative risk of 22% versus 16% for those older than 50 years. [74]  Secondary cancers tend to be confined to the rectum, bladder, lungs, and genitals. Other retrospective studies have shown an increase in leukemia risk, which peaks around 5 to 10 years after treatment. [75] Limiting normal organ doses may help to reduce the risk. 

Ovarian failure

Radiation-induced ovarian failure typically occurs within 6 to 12 months after radiation. Minimum doses for ovarian failure are inversely related to age ranging from 20.3 Gy at birth to 14.3 Gy at the age of 30 years. [76] The doses used for cervical cancer can easily precipitate ovarian failure. Premenopausal patients have several options for preserving ovarian function, namely definitive surgery or ovarian transposition. Laparoscopic ovarian transposition allows the ovaries to be placed outside the radiation field, usually 3 cm away. This procedure is also useful for fertility preservation. The functional preservation rate is approximately 80%. Ovarian cryopreservation is another option. Exogenous hormonal supplementation with estrogen should be considered to prevent osteoporosis and osteopenia and to maintain libido.

Vaginal stenosis

Vaginal stenosis and vaginal canal shortening can develop over months to years after treatment. Stenosis can make it difficult for intercourse and gynecological exams. Consistent use of a vaginal dilator is typically recommended; however, compliance is highly variable. Sexual dysfunction is quite common, ranging from a lack of desire for sexual activity to a lack of adequate vaginal lubrication.

Bone fracture

Pelvic radiotherapy can increase the risk of pelvic fractures, with most fractures occurring at dose levels of 45 to 63 Gy. Bone health is another concern in patients who undergo radiation to the pelvis. Approximately 10% of patients radiated for cervical cancer experience a pelvic fracture. The most common fracture site is the sacrum, most occurring within 2 years after treatment. Bone mineral density scans and appropriate intervention to maintain bone health may help to reduce this risk.

Uterine perforation

Uterine perforation is a complication related to BT applicator insertion and results in excessive doses to normal tissues, poor target coverage, bleeding, and infection. Rates of perforation range from 2% to 18%. [77] [78] [79]  Management is controversial, ranging from postponement of BT to allow for healing to outright abandonment of the procedure. However, treatment delays are known to adversely affect patient outcomes. The risk of vascular and organ injury is low when a blunt instrument causes perforation. Stable patients without signs of infection may be discharged and observed. Prophylactic antibiotics may be prescribed. Signs of hemodynamic instability and infection warrant more aggressive approaches with IV fluids, antibiotics, and surgical exploration.

• Medical Oncology

Definitive Therapy

The Radiation Therapy Oncology Group (RTOG) trials established the utility of platinum-based chemotherapy regimens. Compared with radiotherapy alone, there are consistent overall survival, disease-free survival, and local control advantages. [51] It is postulated that chemotherapy acts as a radiosensitizer. The most common agent used is weekly cisplatin. Single-agent platinum-based regimens have the best progression-free survival and overall survival compared to non-platinum-based regimens and a better toxicity profile than combinations of platinum-based regimens such as cisplatin/5-FU/hydroxyurea. [80] Carboplatin may also be used in patients who cannot tolerate cisplatin. Some practices continue to use a combination of cisplatin/5-FU. This regimen is delivered concurrently with radiotherapy.

Adjuvant Therapy Chemoradiotherapy may be added after surgical resection should the patient have high-risk features. Overall survival and progression-free survival benefits have been demonstrated with the addition of chemotherapy to radiotherapy in certain high-risk postoperative patients. [54]

The use of adjuvant chemotherapy after definitive chemoradiation continues to be investigated in clinical trials. The results have been mixed. Adding adjuvant carboplatin/taxol to chemoradiation for locally advanced cervical cancer resulted in higher rates of grades 3 to 5 toxicity and no difference in overall survival or progression-free survival. Another trial using concurrent and adjuvant cisplatin/gemcitabine demonstrated improved 3-year progression-free survival but markedly higher rates of grades 3 to 4 toxicity and hospitalizations. [81] RTOG 0724 is an ongoing trial investigating the use of adjuvant cisplatin/paclitaxel after definitive chemoradiation in high-risk postoperative patients ( NCT00980954 ).

Recurrence and Metastasis

In recurrent and metastatic disease settings, patients who are not candidates for exenterative surgery or radiotherapy may receive systemic therapy alone. Many patients have previously received single-agent cisplatin-based therapy; therefore, multidrug regimens are typically used. Cisplatin/paclitaxel has been shown to improve progression-free survival in patients with recurrent cervical cancer but yields no difference in median overall survival. [82]  Although other drug combinations such as cisplatin/topotecan, cisplatin/gemcitabine, and cisplatin/vinorelbine are potential options, the Gynecologic Oncology Group (GOG) has suggested that these regimens are not superior to cisplatin/paclitaxel (protocol 204). [83]  Incorporating biological agents such as vascular endothelial growth factor receptor antagonists like bevacizumab into standard chemotherapeutic regimens has improved overall survival. [84]  Immunotherapy with PD-1 inhibition has also been incorporated into chemotherapeutic regimens. Single-agent pembrolizumab has an objective response rate of 12% to 14% in patients with recurrent or metastatic cervical cancer. [85]  Keynote-826, a randomized, double-blinded phase 3 study, demonstrated the addition of pembrolizumab to multidrug chemotherapy improved overall and progression-free survival. [86]  Follow-up subgroup analysis confirmed this finding in a Japanese population. [87]

• Complications

The most commonly used platinum-based drugs are cisplatin and carboplatin. Common adverse effects include neutropenia, thrombocytopenia, anemia, febrile neutropenia, nephrotoxicity, neurotoxicity, and infection. Although cisplatin is the drug of choice, carboplatin can be used in patients who may not tolerate cisplatin, particularly if they already have underlying renal disease.  Carboplatin is thought to have lower efficacy than cisplatin; however, prospective data suggest noninferiority in effectiveness and a statistically significant lower incidence of febrile and nonfebrile neutropenia and creatinine elevation. [88]

Bevacizumab carries the risk of hypertension, hemorrhage, thromboembolic events, renal injury, and ovarian failure in premenopausal women. Pembrolizumab is known for precipitating autoimmune phenomena such as pneumonitis, colitis, hepatitis, nephritis, and endocrinopathies.

The International Federation of Gynecology and Obstetrics (FIGO) staging system was updated in 2018 and remains the dominant staging methodology. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual also has a tumor-node-metastasis classification system in which the tumor stages correspond with the FIGO stages; however, it is not regularly used.

FIGO Staging

Classically, FIGO staging would rely on clinical examination, cystoscopy, proctoscopy, hysteroscopy, urography, and plain film x-ray. These relatively basic tests were utilized so developing countries with fewer healthcare resources could adequately stage patients. More recently, advanced imaging techniques such as MRI and PET scans have become part of the staging workup. MRI is preferred for establishing the tumor stage, given superior tissue delineation compared with CT scan with contrast. [89] [90]

Stage I  

• The disease is strictly confined to the cervix, with the A/B designation indicating the depth of invasion (≤5 or >5 mm).

Stage II  

• The disease invades beyond the uterus but has not extended into the lower vagina.
• This stage also has an A/B designation based on involvement of the parametria.

Stage III  

• The disease has extended to the lower one-third of the vagina (IIIA) or to the pelvic side wall and/or hydronephrosis (IIIB).

Classically, nodal disease did not influence the FIGO staging system; however, it has been shown that nodal disease is one of the most important prognostic indicators for reduced 5-year overall survival. [91]  As a result, new stages (IIIC1 and IIIC2) were added to reflect the involvement of pelvic or PA nodes, respectively.

Stage IVA  

• The disease is locally aggressive, involving adjacent organs such as the bladder or rectum. 

Stage IVB  

• The disease has spread to other solid distant organs; this stage can also be indicative of nonregional nodal disease.

Multiple factors contribute to differences in patient outcomes. Potential prognostic factors for cervical cancer patients include disease stage, number of retrieved lymph nodes, use of a uterine manipulator in laparoscopic treatment, age, race, ethnicity, general health before diagnosis, and access to evidence-based care. These prognostic factors highlight opportunities to enhance care and improve overall mortality.

When diagnosed early, the 5-year relative survival rate for cervical cancer is approximately 92%. About 44% of cervical cancer patients are diagnosed at an early stage. Inconsistent screening is an independent risk factor for late diagnosis. [92]  A higher stage at presentation decreases survival and increases the chance of recurrence. The 5-year relative survival rate drops to 60% when cervical cancer is diagnosed after it has spread locally or spread to regional lymph nodes. With distant metastasis at diagnosis, the 5-year relative survival rate is 19%.

Studies show certain surgical factors affect survival. It is believed that the number of retrieved lymph nodes corresponds to the thoroughness of surgical treatment. Research indicates that a higher retrieved lymph node count has a statistically significant positive effect on progression-free survival. For women having laparoscopic surgery, the use of a uterine manipulator is associated with a better prognosis. [93]

Survival rates also differ based on race. The 5-year relative survival rate is 67% for women of all races. Black women tend to have the highest mortality and lowest survival rate, with a 5-year relative survival rate of approximately 56%. [11] [94]

Patient age at diagnosis also contributes to differences in prognosis and survival, independent of disease stage and histology. Older age is associated with lower survival rates. Patients younger than 50 years, aged 50 to 64 years, and 65 years and older have relative 5-year survival rates of 77%, 61%, and 46%, respectively. Studies indicate older women are a high-risk subset, often receive suboptimal treatment, and die more frequently. Even with BT alone, older women with cervical cancer obtain significant survival benefits. [95]

Complications of advanced disease and associated treatments are similar to other cancers. These late complications may include renal failure, hydronephrosis, pain, lymphedema, bleeding disorders, and fistulas (see Image. Secondary Lymphedema). [96]

• Deterrence and Patient Education

Traditional and innovative patient education methods can increase overall awareness of cervical cancer and the need for prevention and early screening. [97] [98]  Literature shows that healthcare professionals may not consistently recommend or discuss HPV vaccination with all target patients. Some women and parents of young daughters may also have reservations about vaccinations that prevent them from being vaccinated. Additional medical education for clinicians serving high-risk populations may increase awareness, prevention, and screening of those patients at risk for the highest mortality. [99]  

Although a patient may prefer counseling directly from the healthcare professional, additional community outreach efforts are necessary. Culturally sensitive information, appropriate language to reach lower health literacy populations, and targeted efforts to reach women not yet sexually active are needed to expand patient awareness and education and to initiate screening beyond the clinical setting. [100] [101]

• Pearls and Other Issues

Primary prevention of cervical cancer involves HPV vaccination to prevent cervical cancer. The estimated effectiveness of HPV vaccination is 90%. [102]  A quadrivalent vaccine that prevents cervical cancer and genital warts caused by low-risk HPV types is widely available in the United States. The recommended and approved age for vaccination is 9 to 45 years for both females and males. Vaccination can significantly impact cervical cancer mortality in women in low-resource areas and those in high-risk racial and ethnic groups. A vaccine covering only HPV-16 and -18 is no longer marketed in the United States. However, its use may continue in areas outside the United States.

• Enhancing Healthcare Team Outcomes

The interprofessional team can provide public health education and multidisciplinary care to improve cervical cancer awareness, prevention, screening, and management. [103] [104] [105]  Primary care clinicians performing cervical cancer screening, colposcopies, and LEEP procedures, must have ongoing dialogues with gynecologists about findings of suspicious cervical lesions, management, and treatment. Appropriate protocols and guidelines across healthcare systems can improve outcomes by optimizing treatment and follow-up. Developing a culturally sensitive system directed at increasing patient-centered education will require the input of diverse healthcare professionals and staff with multilingual skills and cross-cultural competency.

The interprofessional team can optimize the treatment of patients with cervical cancer through communication and coordination of care. Primary care physicians, gynecologists, gynecologic oncologists, radiation oncologists, and advanced practice practitioners provide diagnoses and care plans. Specialty care, ambulatory care, and oncology nurses should work with the team to coordinate care, support patient education, and provide feedback to the rest of the team. Pharmacists should evaluate vaccinations and medications, recognize drug-to-drug interactions, provide patient education, and monitor compliance. Together, the team can improve outcomes for patients with cervical cancer. 

• Review Questions
• Access free multiple choice questions on this topic.
• Access free CME on this topic.
• Comment on this article.

Invasive Cervical Cancer. Colposcopic view of the cervix in a patient with invasive cervical cancer. Centers for Disease Control and Prevention (CDC)

Secondary Lymphedema. Lymphedema related to cervical cancer treatment. Contributed by Molly Nettles, OTR/L, CLT-LANA

Disclosure: Josephine Fowler declares no relevant financial relationships with ineligible companies.

Disclosure: Elizabeth Maani declares no relevant financial relationships with ineligible companies.

Disclosure: Charles Dunton declares no relevant financial relationships with ineligible companies.

Disclosure: David Gasalberti declares no relevant financial relationships with ineligible companies.

Disclosure: Brian Jack declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Fowler JR, Maani EV, Dunton CJ, et al. Cervical Cancer. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

In this Page

Bulk download.

• Bulk download StatPearls data from FTP

Related information

• PMC PubMed Central citations
• PubMed Links to PubMed

Similar articles in PubMed

• Cervical Cancer (Nursing). [StatPearls. 2024] Cervical Cancer (Nursing). Fowler JR, Maani EV, Dunton CJ, Gasalberti DP, Jack BW, Miller JL. StatPearls. 2024 Jan
• Atypical Squamous Cells of Undetermined Significance. [StatPearls. 2024] Atypical Squamous Cells of Undetermined Significance. Ndifon CO, Al-Eyd G. StatPearls. 2024 Jan
• Review Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: A Systematic Evidence Review for the U.S. Preventive Services Task Force [ 2018] Review Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: A Systematic Evidence Review for the U.S. Preventive Services Task Force Melnikow J, Henderson JT, Burda BU, Senger CA, Durbin S, Soulsby MA. 2018 Aug
• Anal dysplasia screening: an evidence-based analysis. [Ont Health Technol Assess Ser....] Anal dysplasia screening: an evidence-based analysis. Medical Advisory Secretariat. Ont Health Technol Assess Ser. 2007; 7(4):1-43. Epub 2007 Jun 1.
• Review Screening for Cervical Cancer: A Decision Analysis for the U.S. Preventive Services Task Force [ 2011] Review Screening for Cervical Cancer: A Decision Analysis for the U.S. Preventive Services Task Force Kulasingam SL, Havrilesky L, Ghebre R, Myers ER. 2011 May

Recent Activity

• Cervical Cancer - StatPearls Cervical Cancer - StatPearls

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Connect with NLM

National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894

Web Policies FOIA HHS Vulnerability Disclosure

Help Accessibility Careers

Cervical Cancer Disparities: What to Know and Tips for Prevention 

Cervical cancer is caused by a virus called HPV (human papilloma virus) that is spread through sexual contact. For many people, the virus is cleared by the immune system. But if it isn’t, it can develop into cancer.  

The virus can be detected through HPV screening that inspects a sample of cervical tissue for the virus. The test is ordered by a primary care physician or gynecologist who typically collects a sample of cervical tissue as part of a pelvic exam. However, HPV tests can also be done using self-collected samples.  

Cancer of the cervix affects about 13,960 people per year in the United States. The number of cases has dropped dramatically since the 1970s due to screening and due to the HPV vaccine, which prevents infections.  

However, disparities persist. For example: 

• People from historically marginalized groups have lower rates of receiving the HPV vaccine.  
• Black patients are more likely to be diagnosed with more advanced disease and face a higher risk of death from the disease than white patients.  
• Hispanic/Latinx patients and Native American patients are also at a higher risk of death.  
• People who are uninsured, who don’t have a regular healthcare provider, who have experienced trauma, or who have been historically marginalized often experience delays receiving a definitive diagnosis, and therefore may experience delays in treatment.  

Dana-Farber gynecologic oncologists are working to reduce disparities by lowering the barriers patients face when trying to access screening and care. One strategy supported by Dana-Farber’s Cancer Care Equity Program and the Gynecologic Oncology Program is the employment of patient navigators who can help patients in many ways.  

Patient navigators at Dana-Farber have helped patients by:  

• Reaching out and learning specifically about a patient’s needs. 
• Arranging transportation. 
• Providing appointment reminders. 
• Attending appointments to provide support. 
• Arranging translators. 
• Connecting patients to social workers and resource that can help with food insecurity and housing.  

“If you are encountering obstacles that are interfering with your care, ask your cancer team if they have a patient navigator,” says Alexi Wright, MD, MPH , a gynecologic oncologist and director of Gynecologic Oncology Outcomes Research in the Gynecologic Oncology Program at Dana-Farber. “Navigators are increasingly available and can make a big difference for some of the most vulnerable members of our community.” 

Here are other things you can do to prevent and manage cervical cancer. 

For those under 26: Focus on prevention 

The HPV vaccine is a recommended routine vaccination at age 11 or 12, and can be started as early as age 9, according to the Centers for Disease Control and Prevention. People as old as 26 can receive the vaccine.  

“Cervical cancer is a preventable disease that we must eradicate within our lifetime with vaccination,” says Wright.  

Adults: Focus on screening  

Cervical cancer is highly treatable when it is found early, so screening regularly is essential. Any person with a cervix should be screened regularly between the ages of 21 and 65, regardless of their current sexual activity. 

Screening for cervical cancer is typically done during a pelvic exam performed by a primary care physician or a gynecologist. The test can include:  

• A Pap test, which checks for changes in the cells of your cervix that could turn into cancer. 
• An HPV test, which tests for the presence of the HPV virus that causes cervical cancer. 

For patients who want to be tested but prefer not to have a pelvic exam, talk to your doctor about a self-collection kit for you to use to complete HPV testing.  

The American College of Obstetricians and Gynecologists recommendation for cervical cancer screening is:  

• Ages 21-29: Pap test every 3 years. 
• Ages 30-65: A Pap test every 3 years or HPV testing every 5 years; or co-testing with an HPV test and a Pap test every 5 years. 
• Ages 66 and over: No screening required if prior tests have been negative. 

For patients who have had a hysterectomy with removal of the cervix, no screening is required if there is no history of precancerous cervical lesions or cervical cancer. 

Screening is preventive medicine and should be covered by all forms of medical insurance. In addition, many states provide free screening and diagnostic services for breast and cervical cancer for people who qualify based on income, insurance status, and residency. 

Learn more about free breast and cervical cancer screening and resources in Massachusetts. Help is available by phone in English, Spanish, Portuguese, Vietnamese, and Haitian Creole. 

Older adults: Continue gynecologic care 

Approximately 20% of cervical cancer cases are diagnosed in people over age 65, so it is important to continue paying attention to your gynecologic health as you age.  

Pap tests and HPV tests are not recommended for patients over 65, but regular pelvic exams should be continued. If you have a new sexual partner, talk to your doctor about whether a Pap test or HPV test is recommended. 

If you are diagnosed with cervical cancer 

If you are diagnosed with cervical cancer, follow up with an oncologist immediately to learn more and begin treatment. 

Learn more about cervical cancer diagnosis and treatment at Dana-Farber. 

If you are running into challenges that are preventing you from getting treatment — including concerns about insurance, language barriers, transportation challenges, or a living situation that makes cancer care difficult — please request help from your providers. 

At Dana-Farber, our patient navigators have helped nearly 100 patients over the past year access many resources. Patient navigators have helped reduce the number of patients who miss appointments by helping with transportation, care coordination and logistics, and reminders.  

Transportation seems small but it is a big barrier that can prevent patients from getting to appointments. For instance, Uber rides funded by Dana-Farber’s Cancer Care Equity Program helped patients without transportation get to their appointments.  

“We want to make sure there’s nothing stopping patients from getting the care they need,” says Imani Holloman, a patient navigator for the Cancer Care Equity Program in the Gynecologic Oncology Program at Dana-Farber. “This work is beautiful and gives me a chance to be there for people who need it. Sometimes you just need a hand to hold through it all.”  

About the Medical Reviewer

Dr. Wright is an Associate Professor of Medicine at Harvard Medical School and  Dana-Farber Cancer Institute.  She received her Medical Degree from University of Pennsylvania and completed a residency in Internal Medicine at Brigham and Women’s Hospital and a Medical Oncology fellowship at Dana-Farber Cancer Institute.   She also obtained a Masters in Public Health at the Harvard School of Public Health. In 2009 she joined the faculty of Dana-Farber Cancer Institute, where she is a practicing medical oncologist who specializes in gynecologic oncology and health outcomes research. 

2 thoughts on “Cervical Cancer Disparities: What to Know and Tips for Prevention ”

“This site is a treasure! I’d love to receive your newsletter updates.”

Hi Melaine, Thank you for your feedback, we will add you to our list to receive newsletters. Best, BL

Leave a Comment Cancel reply

• Adolescent and Young Adult Cancer
• Bile Duct Cancer
• Bladder Cancer
• Brain Cancer
• Breast Cancer
• Cervical Cancer
• Childhood Cancer
• Colorectal Cancer
• Endometrial Cancer
• Esophageal Cancer
• Head and Neck Cancer
• Kidney Cancer
• Liver Cancer
• Lung Cancer
• Mouth Cancer
• Mesothelioma
• Multiple Myeloma
• Neuroendocrine Tumors
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer
• Skin Cancer/Melanoma
• Stomach Cancer
• Testicular Cancer
• Throat Cancer
• Thyroid Cancer
• Prevention and Screening
• Diagnosis and Treatment
• Research and Clinical Trials
• Survivorship

Request an appointment at Mayo Clinic

HPV-related head and neck cancer treatment is improving, but prevention is best

Share this:.

Editor's note: April is Head and Neck Cancer Awareness Month.

By Jessica Saenz

Head and neck cancers are cancers in the mouth, throat, sinuses and salivary glands. Most often, these cancers develop in the squamous cells lining the nose, mouth and throat.

Head and neck cancers have common risk factors, including tobacco and alcohol use, environmental factors, and exposure to human papillomavirus (HPV) . HPV has been linked to cancers that affect the oropharynx, the part of the head and neck that includes the tonsils, the back of the tongue, the soft palate and the side and back wall of the throat.

Katharine Price, M.D. , a Mayo Clinic medical oncologist, says that while head and neck cancer treatment has come a long way, prevention is always better. Here's what she wants you to know:

The HPV vaccine can prevent head and neck cancer.

HPV is the most common sexually transmitted infection, and nearly everyone will be exposed to it at some point in their life, according to the Centers for Disease Control and Prevention (CDC) . Most of the time, the body's immune system will clear the virus, but it lingers in about 10% of the population without causing symptoms.

HPV is thought to cause about 60% to 70% of oropharyngeal cancer, a type of throat cancer . "The virus incorporates into the body, causing cancer 20 or 30 years later," says Dr. Price.

"People with HPV cancer will ask, 'Is this a new infection?' The answer is no. This is something they were exposed to decades ago." Dr. Katharine Price

Because it's so common, it's difficult to prevent HPV exposure, but you can prepare your immune system by getting the HPV vaccine . "We use the HPV vaccine to prevent HPV-associated cancers," says Dr. Price. "These vaccines get your immune system to recognize and fight specific antigens. Antigens are how the immune system recognizes something abnormal or foreign."

For maximum effectiveness, the HPV vaccine should be given before people become sexually active. The CDC recommends vaccination starting as early as 9, but it can be beneficial through age 45 . HPV vaccine is part of routine recommended childhood vaccinations for all boys and girls ages 11 to 23. If you haven't been vaccinated for HPV, ask your healthcare professional if it's right for you.

Head and neck cancer is often curable, but treatment can have lasting side effects.

Head and neck cancers have high cure rates with proper treatment . However, approaches like surgery, radiation and chemotherapy can have lasting side effects , including dry mouth, altered taste and difficulty chewing, swallowing, or speaking.

When head and neck cancers spread to the lymph nodes, the lymph nodes might need to be treated with radiation therapy or removed. This can lead to lymphedema , tissue swelling caused by an accumulation of fluid that's usually drained through the body's lymphatic system. It can also cause fibrosis, which is the stiffening of the neck tissues.

Head and neck cancer is often diagnosed after it has spread to the lymph nodes. "About 80% of the time, it will spread into lymph nodes in the neck, and the cancer grows there," says Dr. Price. Head and neck cancer that has spread to the lymph nodes is typically treated with a combination of surgery, radiation therapy and chemotherapy, she says.

HPV-related head and neck cancer will spread to other parts of the body in up to 20% of people who receive the diagnosis.

"We have to tailor treatment based on the person. If cancer has spread to another organ, we usually rely on systemic therapy — a drug that goes everywhere in the body through the bloodstream," says Dr. Price. Examples of systemic therapy include immunotherapy , which uses the body's immune system to kill cancer cells, chemotherapy and targeted therapies that attack specific molecular pathways in cancer cells.

New treatments and research are giving people with head and neck cancer more options.

Dr. Price says immunotherapy has become more widely available and has helped change and improve how head and neck cancers are treated. "The year 2016 was a big pivot point because that's when the Food and Drug Administration approved immunotherapy — pembrolizumab — for the treatment of advanced head and neck cancer," she says. "What's exciting now in research and development is the next generation of immunotherapy drugs. We're getting more creative in engaging the immune system to fight the cancer."

Cancer vaccines are another exciting area of research, says Dr. Price. Some people with HPV-related head and neck cancer have a higher risk of recurrence. David Routman, M.D. , a Mayo Clinic radiation oncologist, is leading a study investigating the use of an HPV vaccine with or without immunotherapy before surgery to prevent recurrence of throat cancer.

Distinguishing between HPV-negative and HPV-related head and neck cancer has also improved treatment. "They have a different biology, and HPV-related head and neck cancers respond better to treatment. They tend to have a higher cure rate," says Dr. Price. For example, a new approach developed by Mayo Clinic called de-escalated adjuvant radiation therapy (DART) for HPV-related throat cancer can give patients fewer long-term side effects and better outcomes .

HPV vaccine hesitancy may contribute to head and neck cancers in the future.

Dr. Price says people often relate HPV to cervical cancer and might overlook HPV vaccination for boys, but it's important to vaccinate all children. "If we look at cancers caused by HPV, the single greatest group of people who get HPV cancer in any given year are men with HPV-associated head and neck cancer, so we need to vaccinate boys."

"If we look at cancers caused by HPV, the single greatest group of people who get HPV cancer in any given year are men with HPV-associated head and neck cancer, so we need to vaccinate boys." Dr. Katharine Price

Also, people who are married or in monogamous sexual relationships might think the vaccine wouldn't benefit them. Still, Dr. Price says having even one sexual partner doubles the risk of HPV, and life circumstances can change. Divorce or the death of a spouse could mean you might go back into the dating pool and be exposed to HPV again. "You might be exposed the second time in the middle part of your life, which could lead to cancer in your 70s. Protecting yourself makes sense because you don't know what's around the corner. Get vaccinated up to age 45 if you haven't already."

Dr. Price says some parents hesitate to vaccinate their children against HPV because they worry it will lead to sexual activity at a young age, but she reassures parents that this is not the case. "Many studies have looked at children who were vaccinated and others who weren't, and they didn't show any increase in high-risk sexual activity or behavior in those who were vaccinated," she says. "This vaccine can prevent cancers that cause a significant amount of death and suffering."

Watch this "Mayo Clinic Minute" video to hear Dr. Price discuss HPV-related throat cancer and the importance of prevention with the HPV vaccine:

Learn more about  head and neck cancers  and find a  head and neck cancer  clinical trial at Mayo Clinic.

Join the  Head and Neck Cancer Support Group  on Mayo Clinic Connect.

Also, read these articles:

• Mayo Clinic Minute: 3 ways to prevent head and neck cancer
• Protecting yourself against HPV
• Innovative technology to treat head and neck cancers
• Protecting kids from cancer with HPV vaccine
• Dear Mayo Clinic: Defining head and neck cancer
• Less is more: The new approach to treating HPV-related throat cancer

Related Posts

Researchers are studying a risk-prediction tool that could help healthcare professionals better assess which patients need screening.

Dr. Derek Ebner discusses colorectal cancer in adults under 50, the warning signs, and the importance of seeking medical treatment without delay.

Dr. Janani Reisenauer, a Mayo Clinic thoracic surgeon, discusses innovation in lung cancer screening and treatment.

Request an appointment   Clinical Trials   Give Now

Ginny L. Clements Breast Cancer Research Institute

Researchers identify key bacteria in Latina study participants’ cervicovaginal microbiome linked to HPV and cervical cancer

Latina women experience disproportionately higher rates of human papillomavirus called HPV, precancerous cervical cell growth called dysplasia and cervical cancer compared to other racial and ethnic groups.

After completing a systematic review, University of Arizona researchers found 42 unique bacteria in the cervical and vaginal microbiome of 131 premenopausal Latina women in 10 countries. From those results, they found 16 bacteria with HPV, 24 unique bacteria with abnormal cytology or dysplasia, and five bacteria that are connected to cervical cancer.

“Our studies and this systematic review suggest that persistence and cancer is influenced by specific vaginal bacteria,” said lead researcher Melissa Herbst-Kralovetz , PhD. “There were seven bacteria that were consistently reported across studies, and that gives us insights on what to focus on moving forward.”

They published their findings in the Journal of Epidemiology and Global Health that research into cervical and vaginal microbiome is crucial to better understanding the role of the microbiome in HPV infection, cervical dysplasia and cervical cancer worldwide, especially in Latina women.

According to Dr. Herbst-Kralovetz, professor of basic medical sciences in the  University of Arizona College of Medicine – Phoenix and director of the Translational Women’s Health Research Program on the medical campus, their research addresses important health disparities in this historically understudied, underrepresented and underreported population of women.

Postdoctoral researcher Nicole Jimenez , PhD, BIO5 Institute postdoctoral research associate in the Herbs-Kralovetz lab and department of obstetrics and gynecology, said that since Hispanic individuals are 40% more likely to be diagnosed with cervical cancer than non-Hispanic white individuals, the researchers sought to find out if these same trends from previous systematic reviews were comparable in Hispanic populations or if other patterns would emerge.  

“We found that there are similar trends of dysbiotic bacteria that are more prevalent or abundant in HPV infection and malignant disease,” Dr. Jimenez said. “However, what was most notable to me was that there are not many studies being conducted on HPV or cervical cancer and the microbiome in Hispanic populations.” 

Their goal is to better inform cervical cancer prevention strategies in Latina women.

“I think one of our important findings was a call to action for future robust and standardized investigation in this area and to include not just race and ethnicity characteristics but also sociocultural factors as well,” she said.

Connecting a systematic study to earlier work

Every year about 14,000 women are diagnosed with cervical cancer in the United States and more than 4,000 women die from it. Human papillomavirus is almost always the cause of cervical cancer.

Dr. Herbst-Kralovetz said her team has been working on the vaginal microbiome and its influence in HPV progression to cancer for about 14 years. 

“Most HPV infections are cleared [from the vagina with] no problem. About 90% of people who get exposed to HPV clear it,” she said. “That other 10% has persistent HPV infection that may develop into dysplasia and ultimately cancer.”

She said about 12 years ago, she embarked on clinical study with clinical collaborator, Dana Chase , MD, now at the University of California, Los Angeles.

After starting with the microbiome, they wanted to learn more about the cervicovaginal microenvironment and its influence in promoting HPV. From a cohort of equal Caucasian and Hispanic women, Dr. Herbst-Kralovetz said they were able to produce seven publications.

Together with other researchers, they analyzed multiple "omics" datasets to develop predictive models of the cervicovaginal microenvironment and identify characteristic features of vaginal microbiome, genital inflammation and disease status.

“We knew that there were specific bacteria in our initial cohort that were associated with Hispanic ethnicity as well as HPV infection and progression to cancer,” she said of the results that prompted the latest systematic study.

Creating a publication to examine Latina women, HPV, and cervical cancer worldwide 

First author Vianney Mancilla , a post-baccalaureate student, joined the Herbst-Kralovetz Lab at the start of the COVID-19 pandemic through the Frontera BLAISER (Border Latino and American Indian Summer Exposure to Research) program to pursue her interest in minority and women’s health. The Frontera BLAISER program is designed for underrepresented undergraduates to prepare them for medical school.

“As an undergrad, it's really an incredible opportunity to be working with the University of Arizona College of Medicine - Phoenix, especially with it being my one of my number one school [in applying to medical school],” Mancilla said. “I'm very thankful for Dr. Herbst-Kralovetz and the lab for allowing me to pursue what I was interested in while also delving deeper into their Latina study population.”

What started as a summer research project for Mancilla’s Frontera BLAISER project quickly evolved into a worldwide systematic review with the collaboration of Melissa Flores , PhD, assistant clinical professor, UArizona Department of Psychology and director of the Health Equity Analytics Lab (HEAL) and Naomi Bishop , associate librarian at the University of Arizona College of Medicine - Phoenix.

“We brought them in for their expertise,” Dr. Herbst-Kralovetz said of Dr. Flores and Bishop. “It's been a great team to work with over the time we conducted this systematic review. And Naomi as our medical librarian was an integral team member to facilitate that process.”

Dr. Herbst-Kralovetz said there were a couple systematic studies already published on the connection between lactobacilli dominance and HPV infection connection, though they were primarily conducted with people who were from European ancestry.

Working with Bishop, the researchers narrowed their results to 25 articles from two databases from January 2000 through November 11, 2022. After searching hundreds of articles, they found only 10 countries that had published on Latinas and the cervical vaginal microbiome and cervical carcinogenesis. 

Future plans

The group’s next step is to take the results from the systematic review and apply them to their earlier work to see if there's specific microbial signatures in the microenvironment that may indicate why they are promoting cervical cancer. 

“The vaginal bacteria that we consistently identified [in the publication] across studies give us insights on where to go next,” Dr. Herbst-Kralovetz said.

Last reviewed: 27 March 2024

Cervical screening

Healthcare professionals play a vital role in supporting people to make informed decisions about participating in cervical screening..

Cervical screening is available to anyone with a cervix between the ages of 25 to 64 in the UK. The cervical screening test facilitates the identification of changes in the cervix which, if left untreated, could develop into cancer.

Landy, R., Pesola, F., Castañón, A. et al. Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case–control study. Br J Cancer 115, 1140–1146 (2016).  https://doi.org/10.1038/bjc.2016.290

Castanon A, Landy R, Sasieni P. By how much could screening by primary human papillomavirus testing reduce cervical cancer incidence in England?. J Med Screen. 2017;24(2):110-112.  https://doi.org/10.1177/0969141316654197

There are a few key questions or misunderstandings that can arise around who is eligible to take part in cervical screening and to help with this we have updated our section on eligibility in the Cervical Good Practice Guide to help health professionals provide the right information to patients.

Download our cervical good practice guide ( PDF , 724 KB )

Overview of UK cervical screening programmes

Read about primary human papillomavirus (HPV) testing and cervical screening coverage.

Encouraging informed participation

The latest evidence on barriers and resources to support informed choices.

Safety netting and screening optimisation

Includes information on safety netting, extending screening intervals and self-sampling.

Information for the public

Find out what cervical screening is, who’s eligible and how to get tested.

You can contact our Strategic Evidence team if you have any questions.

Stay connected

Follow cancer research uk health professionals.

Read news, updates and opinion, posted weekly.

Sign up for our Health Professionals newsletters

Stay up-to-date with the latest cancer research information.

• Health & Fitness

Hope's Heartbeat: After cancer diagnosis and surrogacy, family now fights for research

PHILADELPHIA (WPVI) -- Meet a couple whose whole world changed at precisely the wrong moment.

But now their fighting spirit is entering a new ring.

In 2017, newlyweds Erin and Joey D'Avanzo, of Chester County, were anxiously awaiting a bright future, hoping to expand their family. But when they returned from their honeymoon, they had to prepare for something they never expected.

"I was having some issues. I went to the doctors and we found out that I had stage 1B2 cervical cancer," Erin said. "So from there, I had to go on a treatment plan. I did three rounds of chemotherapy and then it ended with a hysterectomy. So then we knew right from then that I wasn't going to be able to carry a baby. I got some eggs taken out and then we took a pause from there."

When Erin was cancer-free, a hurdle was surpassed triumphantly. Yet they were still so far away from their dream of bringing new life into the world.

"When you would ask me what I wanted to be when I grow up, I would tell you 'mom' as a kid. So it was like, why me? Now everybody around you is getting pregnant, all your friends are getting pregnant. I can't really relate," she said.

But they didn't give up. They found a lovely surrogate from Buffalo, New York, who went on to carry their child.

"We had a phone call with them, and the first phone call we both were like, 'That's her. We want her to carry our baby.' She's amazing," said Erin.

And for all the trials they endured, a serendipitous gift was received when Frankie entered the world on Erin's 33rd birthday last year.

"Our journey was very different, but I actually wouldn't trade it for the world now that we went through it all," she said. "All the years of wanting a baby and waiting for a baby, and then he was finally here and I was just beyond words."

Overwhelmed with gratitude, the couple looked for a way to give back. They found that opportunity for Joey, who is participating in an event held in Philadelphia by "Haymakers for Hope."

"It would be great if there was a way that we could pay this forward to one of my closest friends. He had signed up for this boxing match. It's called Haymakers for Hope . And what this event does is they aim to raise awareness and money for knocking out cancer," Joey said.

Joey signed up as a boxer and has since raised over $7,500 that will go towards research for cancer. He's been getting his gloves on at Knockout Boxing and Fitness in Newark, Delaware. All of this leading up to the event on April 24.

"The number one thing is this is all for my wife, just as a way to kind of honor what she went through. As I always say, she had the toughest fight, just like any other cancer patient and other people that have diseases that can really disrupt her life. So seeing her go through all those steps, the chemo, then the surgery, and just how she handled it with grace and strength, for me -- now it's my turn to get in the ring."

Hope's Heartbeat: Share Your Story with Action News

Do you know someone who has triumphed when faced with a life-threatening situation?

If so, Action News wants to tell their story! What are the lessons learned that they can share with others? Let us know in the form below:

Related Topics

• PHILADELPHIA
• CHESTER COUNTY
• HEALTH & FITNESS
• FAMILY & PARENTING

NJ mom shares pregnancy experience during Black Maternal Health Week

Human infections from rat urine on the rise in New York City

Here's how to reduce stress and get your taxes done

Man accused of posing as nurse allegedly assaulted 12 other women

Top stories.

Philly man pleads guilty in DUI crash that killed mother of 5

• 2 hours ago

Voorhees Town Center closed for weekend after 2-alarm fire

Jalen Hurts donates $200K for air conditioning units at 10 schools

Ex-Philly officer pleads guilty in shooting death of 12-year-old boy

Man sets himself on fire outside courthouse where Trump is on trial

New Yorkers weigh in on Knicks-76ers playoff series

Man killed in fire that damaged part of Atlantic City boardwalk

American announces round trip flight to Brazil for Eagles fans

• 25 minutes ago