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The exact cause of most vaginal cancers is not known. But scientists have found that it is linked to a number of conditions described in Risk Factors for Vaginal Cancer Research is being done to learn more about how these risk factors cause cells of the vagina to become cancer.

About 75% of vaginal cancers are caused by the human papillomavirus (HPV). Research has shown that normal cells make substances called tumor suppressor gene products to keep from growing too rapidly and becoming cancers. High-risk HPV (human papillomavirus) types (like HPV 16 and HPV 18) produce 2 proteins (E6 and E7) that can change the way tumor suppressor gene products work. When this happens, the tumor suppressor gene products are no longer able to control growth of normal cells into cancer cells.

Women who were exposed to diethylstilbestrol (DES) as a fetus (that is, their mothers took DES during pregnancy) are at increased risk for developing vaginal clear cell carcinoma. DES also increases the likelihood of vaginal adenosis (gland-type cells in the vaginal lining rather than the usual squamous cells). Most women with vaginal adenosis never develop vaginal clear cell carcinoma. Still, those with a rare type of adenosis called atypical tuboendometrial adenosis do have a higher risk of developing this cancer.