Mutations in TP53 are a negative prognostic factor in HNSCC and are observed more commonly in (i) non–HPV-associated vs. HPV-positive HNSCC, (ii) in men vs. women, and (iii) in tumors associated with repeated exposure to carcinogens such as those arising in the larynx, tongue, and oral cavity [33,40,41,42]. This evidence concerns the gene TP53 and head and neck squamous cell carcinoma.