Human Papillomavirus-Independent Squamous Lesions of the Vulva.

The pathogenesis of vulvar squamous neoplasia has 2 pathways: human papillomavirus (HPV)-dependent and HPV-independent. The HPV-dependent pathway in the vulva follows the same progression as HPV-dependent lesions elsewhere in the gynecologic tract-HPV infection results in high-grade squamous intraepithelial lesion with subsequent progression to basaloid squamous cell carcinoma. The HPV-independent pathway is more complex, with a variety of precursor lesions and molecular alterations. Although the most recognized form of HPV-independent vulvar lesion is differentiated vulvar intraepithelial neoplasia, recent explorations have elucidated new precursors. This review provides an update on HPV-independent risk factors and precursor lesions for squamous cell carcinoma of the vulva.