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What Causes Vulvar Cancer?

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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 progress in understanding how certain changes in DNA can cause normal cells to become cancerous. DNA is the substance 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) have instructions that control 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 two ways. It can either be associated with HPV infection (HPV-positive) or not associated with HPV infection (HPV-negative). 

  • Women with HPV-positive vulvar cancer tend to be younger and often smoke.
  • Women with HPV-negative vulvar cancer tend to be older and often have an inflammatory or autoimmune condition.

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.

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

 

Brinton LA, Thistle JE, Liao LM, Trabert B. Epidemiology of vulvar neoplasia in the NIH-AARP Study. Gynecol Oncol. 2017 May;145(2):298-304..

Madsen BS, Jensen HL, van den Brule AJ, Wohlfahrt J, Frisch M. Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based case-control study in Denmark. Int J Cancer. 2008 Jun 15;122(12):2827-34. doi: 10.1002/ijc.23446. PMID: 18348142.

Last Revised: May 2, 2025

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