Grant: Project Grant

Vulvar cancer, which affects the external genitalia of patients, is an uncommon and understudied cancer. In recent years, we have learned that the most common type of vulvar cancer, vulvar squamous cell carcinoma (VSCC), develops from pre-cancerous lesions via different pathways. One pathway is associated with human papilloma virus (HPV) infection, and these VSCCs are classified as HPV-associated (HPV-A). The second pathway is related to chronic inflammatory skin conditions, not HPV infection, and these VSCCs are classified as HPV-independent (HPV-I). VSCCs arising from these two principal pathways are associated with different risks of cancer recurrence and different responses to treatment. The majority of HPV-I VSCCs have mutations in the TP53 gene. Patients with HPV-I VSCC with TP53 mutations have a higher chance of their cancer recurring compared to HPV-A VSCC patients and need more extensive surgery in order to clear the disease and improve their survival. Despite these acknowledged differences between HPV-I and HPV-A VSCC, currently, management for all VSCCs is the same. This means that individuals with HPV-A VSCC are possibly undergoing unnecessarily disfiguring surgeries, which could include removal of the clitoris, compromise of sexual function, negative impacts on body image, and/or impairment of bowel or bladder function. Also of great concern, it is believed that patients with HPV-I VSCC have been undergoing less aggressive surgery than is needed, leading to higher rates of disease recurrence and death from disease. Our proposed study will determine if personalizing surgical therapy - providing less extensive surgery for HPV-A VSCC patients and more extensive surgery for HPV-I VSCC patients - based on the molecular features relating to HPV and TP53 status will improve outcomes.