TP53 and head and neck squamous cell carcinoma: Carcinogen-driven (i.e., HPV–) HNSCC is largely mediated by loss-of-function mutations in tumor-suppressor genes (e.g., TP53 and CDKN2A), whereas HPV+ HNSCC carcinogenesis is driven by viral oncoprotein–mediated inactivation of tumor-suppressor genes (6).