CDKN2A and neoplasm: Annotation of the HPV status of oropharyngeal cancer is best ascertained by testing tumor tissue (fresh-frozen or formalin-fixed, paraffin-embedded tissue) for overexpression of p16INK4a using immunohistochemistry and the presence of HPV DNA or HPV mRNA by either in situ hybridization or PCR-based methods (Fig. 3).