2026 International Society for the Study of Vulvovaginal Disease terminology for vulvar intraepithelial neoplasia and squamous intraepithelial lesions.

Abstract

The 2026 International Society for the Study of Vulvovaginal Disease terminology for vulvar intraepithelial neoplasia and squamous intraepithelial lesion requires p16 and p53 immunohistochemistry for classification into human papillomavirus-associated or human papillomavirus-independent disease. p16 and p53 are tumor suppressor proteins; block positive p16 staining is a surrogate marker for genomic integration of oncogenic human papillomavirus, while null or overexpressed p53 staining correlates with TP53 mutation. Human papillomavirus-associated and human papillomavirus-independent vulvar intraepithelial neoplasia represent 2 distinct entities with different diagnostic considerations, treatments, surveillance strategies, and prognoses. The designation of 'neoplasia' vs 'lesion' reflects biological behavior, with neoplasia signifying an established risk of progression to cancer. Human papillomavirus-associated disease maintains a 2-tier nomenclature: human papillomavirus-associated vulvar intraepithelial neoplasia for precursors to vulvar squamous cell carcinoma vs low-grade squamous intraepithelial lesion and condyloma for transient human papillomavirus manifestations. While human papillomavirus-associated vulvar intraepithelial neoplasia is preferred, high-grade squamous intraepithelial lesion is retained as acceptable in some settings to maintain consistency with nomenclature for analogous lesions across the lower genital tract. Human papillomavirus-independent disease almost always arises from longstanding lichen sclerosus. The updated terminology for human papillomavirus-independent precursors to squamous cell carcinoma is human papillomavirus-independent vulvar intraepithelial neoplasia, subcategorized as p53 mutant or p53 wild type. Verrucous vulvar intraepithelial neoplasia is a subtype of p53 wild type human papillomavirus-independent vulvar intraepithelial neoplasia and the usual precursor to verrucous carcinoma. Vulvar aberrant maturation encompasses human papillomavirus-independent lesions of uncertain neoplastic potential arising in lichen sclerosus that raise concern for but are not diagnostic of human papillomavirus-independent vulvar intraepithelial neoplasia. Collaboration between clinicians and pathologists is essential to achieve accurate diagnosis, optimal individualized treatment, and consistent application of this terminology in practice and research.