Vulvar Cancer

Epidemiology & Impact

Vulvar cancer accounts for approximately 6,900 new cases and 1,630 deaths annually in the United States, representing about 6% of gynecologic malignancies. Incidence has been increasing, particularly among younger women, reflecting the rising prevalence of HPV infection. Two distinct pathways exist: HPV-associated vulvar cancer (approximately 40-60%, younger women, better prognosis) and HPV-independent vulvar cancer (older women, associated with lichen sclerosus and differentiated vulvar intraepithelial neoplasia, worse prognosis). Squamous cell carcinoma accounts for approximately 90% of vulvar malignancies. The median age at diagnosis is 68 years.

Molecular Biology & Biomarkers

HPV-positive vulvar SCC is driven by E6/E7 oncoproteins and typically has wild-type TP53 with p16 overexpression (used as a diagnostic surrogate for HPV status). HPV-negative vulvar SCC commonly harbors TP53 mutations and CDKN2A alterations. Both subtypes show PD-L1 expression, providing rationale for immunotherapy. PIK3CA mutations are found in approximately 15-20% of vulvar cancers. HER2 amplification occurs in a subset and is a potential therapeutic target. The molecular distinction between HPV-positive and HPV-negative vulvar cancer has prognostic implications and may guide future treatment strategies.

Evolving Treatment Landscape

Early-stage vulvar cancer is treated with surgical excision and sentinel lymph node biopsy, moving away from radical vulvectomy with bilateral inguinofemoral lymphadenectomy to more conservative approaches that reduce morbidity. For locally advanced disease, concurrent chemoradiation with cisplatin or 5-FU/mitomycin mirrors the approach used in anal cancer. For recurrent or metastatic disease, pembrolizumab has shown activity in PD-L1-positive vulvar SCC and is approved for MSI-H or TMB-high tumors through tumor-agnostic indications. Cemiplimab has also demonstrated encouraging results. The rarity of vulvar cancer has limited disease-specific clinical trial development, and treatment advances often draw from cervical and anal cancer paradigms.

Note: There are no tumor-specific FDA-approved novel therapies for vulvar cancer. Treatment is primarily surgery, radiation, and platinum-based chemotherapy. Pembrolizumab is available via the MSI-H/TMB-H tumor-agnostic indication for eligible patients.

EMA-Approved Therapies for Vulvar Cancer

The European Medicines Agency (EMA) regulates drug approvals across the European Union. Below are key therapies with comparative information to FDA approvals.

For complete European drug information, visit ema.europa.eu ↗