Representative cases of NK, NK-M and K histological subtypes of OPSCC K cancer with sheets of compact cells (a), which are p16-positive (b) and HPV DNA ISH-positive (c). Inset shows intranuclear localization of HPV consistent with so-called “integrative” pattern of viral infection. NK-M case (d) is predominantly composed of compact cells mixed by areas with larger cells with more abundant eosinophilic cytoplasm (lower left); NK-M OPSCC are often p16-positive (e), but HPV ISH-negative (f). K carcinoma with typical keratin pearls (g), no p16 immunoreactivity (h), and no HPV ISH signal. Hematoxylin & eosin (a, d, g), p16 immunohistochemistry (b, e, h), high-risk HPV DNA ISH (c, f, i); semi-serial sections, × 100.