The absence of high-risk HPV combined with specific p53 and p16INK4a expression patterns points to the HPV-independent pathway as the causative agent for vulvar squamous cell carcinoma and its precursor simplex VIN in a young patient.

Simplex vulvar intraepithelial neoplasia (VIN) is an important precursor of vulvar invasive squamous cell carcinoma and characteristically occurs in postmenopausal women. In this report, the absence of high-risk human papillomavirus (HPV) combined with specific p53 and p16INK4a expression patterns points to the HPV-independent pathway as the causative agent for vulvar squamous cell carcinoma in a 28-year-old woman. Its precursor simplex VIN was initially interpreted as eczema.