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