What Causes Vulvar Cancer?

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

Researchers have made a lot of progress in understanding how certain 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 look like 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 right time are called tumor suppressor genes.

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. For more on genes and cancer, see Oncogenes and Tumor Suppressor Genes.

Studies suggest that squamous cell cancer of the vulva (the most common type) can develop in at least 2 ways. In up to half of cases, human papillomavirus (HPV) infection appears to have an important role. Vulvar cancers associated with HPV infection (the basaloid and warty subtypes) seem to have certain distinctive features. They are often found along with several other areas of vulvar intraepithelial neoplasia (VIN). The women who have these cancers tend to be younger and often smoke.

The second process by which vulvar cancers develop does not involve HPV infection. Vulvar cancers not linked to HPV infection (the keratinizing subtype) are usually diagnosed in older women (over age 55). These women may have lichen sclerosis and may also have the differentiated type of VIN. DNA tests from vulvar cancers in older women rarely show HPV infection, but often show mutations of the p53 tumor suppressor gene. The p53 gene is important in preventing cells from becoming cancerous. When this gene has undergone mutation, it is easier for cancer to develop. Younger vulvar cancer patients with HPV infection rarely have p53 mutations.

These discoveries have not yet affected treatment. But they may help in finding ways to prevent cancer of the vulva and at some point might lead to changes in treatment.

Because vulvar melanomas and adenocarcinomas are so rare, much less is known about how they develop.