Several risk factors for cancer of the vulva are known, and we are beginning to understand how these factors can cause cells in the vulva to become cancerous.

Researchers have made great progress in understanding how certain known, and we are beginning to understand how these factors can cause cells in the vulva to become changes in DNA can cause normal cells to become cancerous. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance. Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the appropriate time are called tumor suppressor genes. It is known that cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes. Usually DNA mutations related to cancers of the vulva occur during life rather than having been inherited before birth. Acquired mutations may result from cancer-causing chemicals in tobacco smoke. Sometimes they occur for no apparent reason.

Recent studies suggest that squamous cell vulvar cancer (the most common type) can develop in at least 2 ways. In about 1/3 to 1/2 of cases, HPV infection appears to have an important role. Two proteins (E6 and E7) produced by high-risk HPV types can interfere with the functioning of known tumor suppressor gene products (called p53 and Rb). This results in increased cell growth and in failure of cells to die when they become damaged. Vulvar cancers associated with HPV infection seem to have certain distinctive features. Women with these cancers often have multiple areas of VIN elsewhere on their vulvas, are usually smokers, and tend to be younger (age 35 to 55) than typical vulvar cancer patients.

The second process by which vulvar cancers develop does not involve HPV infection. Vulvar cancers not associated with HPV infection usually are diagnosed in older women (age 55 to 85) who rarely have VIN but often have lichen sclerosus. DNA tests from vulvar cancers in older women not infected by HPV often show mutations of the p53 tumor suppressor gene. Younger patients with HPV infection and vulvar cancer rarely have p53 mutations.

These recent discoveries have not yet had any impact on treatment. But, in the future, they will probably be important in developing prevention strategies and in selecting treatment strategies most appropriate for distinct older and younger women with squamous cell vulvar cancer.

Because of their rarity, much less is known about how vulvar melanomas and adenocarcinomas develop.