Traditionally, p16 IHC was used to differentiate high-grade squamous intraepithelial lesion, an HPV-associated squamous lesion of the lower anogenital tract20, and as a surrogate marker for HPV testing in HPV-mediated oropharyngeal squamous cell carcinoma21. This evidence concerns the gene CDKN2A and squamous cell intraepithelial neoplasia.