TP53 and head and neck squamous cell carcinoma: Loss of function of tumor suppressor genes TP53 and CDKN2A (p16Ink4A) through gene mutation, methylation, or in the case of CDKN2A through focal loss of 9p21, are often found in both premalignant cells and HPV-negative HNSCC, and occur early in oncogenesis [3,26,29].