Risk Factors for Vaginal Cancer

Scientists have found that certain risk factors make a woman more likely to develop vaginal cancer. But many women with vaginal cancer don’t have any clear risk factors. And even if a woman with vaginal cancer has one or more risk factors, it’s impossible to know for sure how much that risk factor contributed to causing the cancer.

What is a risk factor?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even many, does not mean that you will get the disease. And some people who get the disease might not have any known risk factors.

Human papillomavirus (HPV)

HPV is short for human papillomavirus. HPVs are a large group of related viruses. Each virus in the group is given a number, which is called an HPV type.

Certain HPV types have been linked with cancers of the cervix and vulva in women, cancer of the penis in men, and cancers of the anus and throat (in men and women). They've also been linked to vaginal pre-cancers (VAIN).  HPV is found in most cases of vaginal cancer. These types are known as high-risk types of HPV and include HPV 16 and HPV 18, as well as others. Infection with a high-risk HPV may have no visible signs until pre-cancerous changes or cancer develops.

Sexual activity with someone who has HPV is the most common way of getting HPV. Thus, having many sexual partners in a person’s lifetime, puts them at higher risk for acquiring HPV. Vaccines have been developed to help prevent infection with some types of HPV. See HPV for more information.

Age

Squamous cell cancer of the vagina occurs mainly in older women. It can happen at any age, but only a few cases are found in women younger than 40. Almost half of cases occur in women who are 70 years old or older.

Diethylstilbestrol (DES)

DES is a hormone drug that was given to pregnant women from the 1940s to early 1970s to prevent miscarriage. The FDA stopped use of this drug in 1971.  Women whose mothers took DES when pregnant with them develop clear-cell adenocarcinoma of the vagina or cervix more often than would normally be expected. There's about 1 case of this type of cancer in every 1,000 daughters of women who took DES during their pregnancy. This means that about 99.9% of DES daughters do not develop this cancer.

DES-related clear cell adenocarcinoma is more common in the vagina than the cervix. The risk appears to be greatest in those whose mothers took the drug during their first 16 weeks of pregnancy. Their average age when they are diagnosed is 19 years.

DES daughters have an increased risk of developing clear cell carcinomas, but women don’t have to be exposed to DES for clear cell carcinoma to develop. In fact, women were diagnosed with this type of cancer before DES was invented.

DES daughters are also more likely to have high grade cervical dysplasia (CIN 3) and vaginal pre-cancers (VAIN 3) when compared to women who were never exposed.

You can learn more in DES Exposure: Questions and Answers.

Vaginal adenosis

Normally, the vagina is lined by flat cells called squamous cells. In about 40% of women who have already started having periods, the vagina may have one or more areas lined instead by glandular cells. These cells look like those found in the glands of the cervix, the lining of the body of the uterus (the endometrium), and the lining of the fallopian tubes. These areas of gland cells are called adenosis. This occurs in nearly all women who were exposed to DES during their mothers’ pregnancy. Having adenosis increases the risk of developing clear cell carcinoma, but this cancer is still very rare. The risk of clear cell carcinoma in a woman who has adenosis that's not related to DES is very small. Still, many doctors feel that any woman with adenosis should have careful screening and follow-up.

Cervical cancer

Having cervical cancer or pre-cancer (cervical intraepithelial neoplasia or cervical dysplasia) increases a woman’s risk of vaginal squamous cell cancer. This is most likely because cervical and vaginal cancers have much the same risk factors, such as HPV infection and smoking.

Some studies suggest that treating cervical cancer with radiation therapy may increase the risk of vaginal cancer, but this was not seen in other studies, and the issue remains unresolved.

Smoking

Smoking cigarettes more than doubles a woman’s risk of getting vaginal cancer.

Alcohol

Drinking alcohol might affect the risk of vaginal cancer. A study of alcoholic women found more cases of vaginal cancer than expected. But this study was flawed because it didn’t look at other factors that can alter risk, such as smoking and HPV infection. A more recent study that did take these other risk factors into account found a decreased risk of vaginal cancer in women who do not drink alcohol at all.

Human immunodeficiency virus (HIV)

Infection with HIV (human immunodeficiency virus), the virus that causes AIDS, increases the risk of vaginal cancer. This is because HIV may prevent the immune system from working well.  If people with HIV are also infected with another virus, like HPV, the immune system would have a hard time getting rid of it, putting the person at higher risk for developing HPV- associated VAIN or HPV-associated vaginal cancer. 

Vaginal irritation

In some women, stretched pelvic ligaments let the uterus sag into the vagina or even extend outside the vagina. This is called uterine prolapse. It can be treated with surgery or by wearing a pessary, a device to keep the uterus in place. Some studies suggest that long-term (chronic) irritation of the vagina in women using a pessary may slightly increase the risk of squamous cell vaginal cancer. But this is very rare, and no studies have clearly proven that pessaries cause vaginal cancer.

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References

Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).

Ao M, Zheng D, Wang J, Gu X, Xi M. Risk factors analysis of persistence, progression and recurrence in vaginal intraepithelial neoplasia. Gynecol Oncol. 2021 Sep;162(3):584-589. doi: 10.1016/j.ygyno.2021.06.027. Epub 2021 Jul 3. Erratum in: Gynecol Oncol. 2022 Aug;166(2):369. doi: 10.1016/j.ygyno.2022.06.009. PMID: 34226020.

Huo D, Anderson D, Palmer JR, Herbst AL. Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: Update after 40-year follow-up. Gynecol Oncol. 2017;146(3):566-571.

SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute; 2024 Apr 17. [updated: 2024 Jun 27; cited 2024 Aug 12]. Available from: https://seer.cancer.gov/statistics-network/explorer/. Data source(s): SEER Incidence Data, November 2023 Submission (1975-2021), SEER 22 registries.

National Cancer Institute. Vaginal Cancer Treatment (PDQ®)–Health Professional Version. February 16, 2024. Accessed at www.cancer.gov/types/vaginal/hp/vaginal-treatment-pdq on August 12, 2024.

Society of Gynecologic Oncology. Vaginal Cancer Risk Factors.  Accessed at www.sgo.org/patients-caregivers-survivors/caregivers/vaginal-cancer-risk-factors/ on August 12, 2024.

 

Last Revised: September 23, 2024

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