Vaginal Cancer Causes and Risk Factors

Vaginal cancer is a rare cancer that begins in the tissues of the vagina. Most vaginal cancers are associated with long-lasting infection with high-risk types of human papillomavirus (HPV), particularly HPV16. HPV is found in approximately 66–74% of invasive vaginal cancers and in about 85–96% of high-grade vaginal precancers (VaIN 2/3). Most HPV infections clear on their own and never cause cancer. However, when a high-risk HPV infection persists, it can cause abnormal cell changes that may develop into precancer. Approximately 5% of high-grade vaginal precancers may eventually progress to invasive cancer. 

Not all vaginal cancers are related to HPV. Some are HPV-independent, meaning they develop through other pathways that are not yet fully understood. Understanding these different pathways helps explain why vaginal cancer can occur both in people with HPV-related disease and in those without evidence of HPV infection. 

What Causes Vaginal Cancer?

Vaginal cancer begins when the genetic blueprint, or DNA, of the cells lining the vaginal wall becomes severely damaged. While the precise biological trigger behind this genetic damage is not yet fully understood, clinical research has established a definitive link to high-risk strains of the Human Papillomavirus (HPV), and in the vast majority of cases, it is a persistent, chronic HPV infection that drives this cellular disruption.

When the virus becomes chronic, it integrates its own genetic material into the host cells, producing specific viral proteins that deactivate the body's natural tumor-suppressor pathways. Without these cellular guardrails, healthy epithelial cells undergo a multi-stage transformation. They begin as precancerous lesions, a state known as vaginal intraepithelial neoplasia (VaIN).

If the immune system or medical interventions do not clear these abnormal cells, they continue to mutate and multiply uncontrollably. Over time, they form a localized mass or tumor that can eventually penetrate deeper into the surrounding muscular walls of the vagina, the lymphatic channels, or distant anatomical structures.

Vaginal Cancer Risk Factors

Having one or more risk factors does not mean that you will develop vaginal cancer. Understanding your risk factors can help you and your healthcare team identify ways to reduce your risk when possible and determine whether you may benefit from closer follow-up based on your individual medical history. 

Risk factors can generally be grouped into two categories: non-modifiable risk factors, such as age and medical history, which cannot be changed, and modifiable risk factors, such as smoking, where changes may help reduce risk. 

Non-Modifiable Risk Factors

Some risk factors for vaginal cancer cannot be changed. These include age, certain medical conditions or exposures, and a history of HPV-related precancer or cancer. 

• Older age: The risk of vaginal cancer increases with age. Most invasive vaginal cancers are diagnosed in women in their late 60s and 70s, although the disease can occur at younger ages. 

• History of vaginal precancer: Women who have had high-grade vaginal precancer (VaIN 2/3 or HSIL) have an increased risk of developing vaginal cancer. Most of these precancerous changes are associated with persistent high-risk HPV infection. 

• History of cervical or other HPV-related precancer or cancer: A history of cervical precancer (CIN), cervical cancer, or precancer or cancer of the vulva increases the risk of vaginal cancer. These conditions share many of the same risk factors, particularly persistent high-risk HPV infection. 

• DES exposure before birth: Diethylstilbestrol (DES) is a medication that was prescribed to some pregnant women in the United States between about 1940 and 1971 to help prevent pregnancy complications. Women exposed to DES before birth have an increased risk of developing a rare type of vaginal cancer called clear cell adenocarcinoma. Although DES exposure increases this risk, clear cell adenocarcinoma remains rare. 

• Vaginal adenosis: Vaginal adenosis occurs when glandular cells are present in areas of the vagina where they are not normally found and is more common in women exposed to DES before birth. Most vaginal adenosis does not become cancer. Certain atypical forms have been associated with clear cell adenocarcinoma, but the overall risk is low. 

• A weakened immune system: Conditions or treatments that suppress the immune system can make it more difficult for the body to clear HPV infection. This includes HIV infection, organ transplantation, and the use of certain medications that suppress the immune system.  

Modifiable Risk Factors

Unlike many common cancers, vaginal cancer has few established lifestyle-related risk factors. Diet, exercise, and body weight have not been clearly linked to the development of vaginal cancer. However, there are steps you can take to reduce your risk, particularly by reducing your risk of HPV infection and avoiding tobacco. 

• HPV exposure: Because most vaginal cancers are associated with high-risk HPV, reducing exposure to HPV may lower your risk. Having multiple sexual partners and becoming sexually active at a younger age are associated with a greater likelihood of HPV exposure. Condom use can reduce but does not completely prevent HPV transmission. 

• HPV vaccination: Vaccination is one of the most effective ways to prevent infection with the high-risk HPV types that cause vaginal and other HPV-related cancers and precancers. The vaccine provides the greatest protection when given before exposure to HPV, but some adults may also benefit from vaccination depending on their age and individual circumstances. 

• Tobacco use: Smoking increases the risk of vaginal squamous cell cancer and may make it more difficult for the immune system to clear a persistent HPV infection. Quitting smoking may help reduce this risk and provide many other important health benefits. 

While vaginal cancer cannot always be prevented, reducing HPV exposure, receiving the HPV vaccine when appropriate, and avoiding tobacco can help lower your risk. There is no routine screening test specifically for vaginal cancer in the general population. Follow recommended cervical cancer screening and any additional surveillance advised by your doctor based on your medical history. Report symptoms such as unusual vaginal bleeding or discharge, pelvic pain, or a vaginal mass to your doctor. 

Can Vaginal Cancer be Prevented?

There is no way to completely prevent vaginal cancer, particularly because some risk factors, such as age and certain medical conditions or exposures, cannot be changed. However, there are steps you can take to reduce your risk, especially for vaginal cancers related to HPV. 

Get vaccinated against HPV: HPV vaccination is one of the most effective ways to prevent infection with the high-risk HPV types that cause most vaginal cancers and precancers. The vaccine works best when given before exposure to HPV. Routine vaccination is recommended at ages 11–12 and can begin as early as age 9. Catch-up vaccination is recommended through age 26, and some adults ages 27–45 may also benefit after discussing vaccination with their doctor. 

Avoid tobacco: Smoking increases the risk of vaginal squamous cell cancer and may make it more difficult for the body to clear an HPV infection. If you smoke, quitting can help reduce your risk and provides many other health benefits.  

Reduce your risk of HPV exposure: Using condoms can lower the risk of HPV transmission, although they do not provide complete protection. Limiting the number of sexual partners can also reduce the likelihood of HPV exposure. 

Keep up with recommended Pap testing and follow-up: There is no routine screening test specifically for vaginal cancer in women at average risk. Pap tests are designed primarily to screen for cervical cancer, but they may occasionally detect abnormal cells from the vagina. Continue Pap and HPV testing according to your doctor’s recommendations. If you are at higher risk for vaginal cancer, your doctor may recommend additional testing or closer follow-up. Women who have had a hysterectomy with removal of the cervix for noncancerous reasons and have no history of high-grade cervical precancer or cancer generally do not need routine Pap or HPV testing. 

Know the symptoms: Because there is no routine screening test for vaginal cancer, promptly report unusual symptoms to your doctor. These may include abnormal vaginal bleeding or discharge, pain during sex, pelvic pain, or a lump or mass in the vagina.  

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Benefit from World-Class Care at Moffitt Cancer Center

At Moffitt Cancer Center, our gynecologic oncology specialists provide expert evaluation and individualized care for women with vaginal precancer or cancer, as well as those who may be at higher risk. Although there is no routine screening test specifically for vaginal cancer, women with certain risk factors may benefit from closer surveillance or additional testing based on their medical history. Pelvic examinations are also important when symptoms are present, such as abnormal vaginal bleeding or discharge, pelvic pain, or a vaginal mass. 

Pap and HPV tests are primarily used to screen for cervical cancer and should be performed according to current screening guidelines. For women at higher risk, recommendations for Pap or HPV testing, pelvic examinations, and other surveillance may differ. Your doctor can determine which examinations and tests are appropriate based on your age, medical history, symptoms, and individual risk factors. 

For women diagnosed with vaginal cancer, Moffitt’s multidisciplinary team provides specialized care and develops an individualized treatment plan designed to achieve the best possible outcome while preserving quality of life. Patients also have access to advanced treatment options and innovative clinical trials that may not be widely available elsewhere. 

Moffitt’s researchers are dedicated to advancing our understanding of how cancer develops, spreads, and can be prevented and treated. By bringing research and clinical care together, promising discoveries can be translated into new approaches to cancer prevention, diagnosis, and treatment. This commitment to research and patient care is reflected in Moffitt’s designation by the National Cancer Institute as a Comprehensive Cancer Center.

If you would like to learn more about vaginal cancer causes and risk factors, a specialist in our gynecological clinic can provide detailed information and create an individualized risk profile for you. To request an appointment, call 1-888-663-3488 or submit a new patient registration form online. No referral is necessary.