p53, RB, p16 and p14 inactivation through mutation, deletion or epigenetic silencing as well as cyclin D1 (CCND1 gene), MDM2 and CDK4 overexpression have been associated with tumorigenesis and/or reduced survival in HNSCC [147,151,162,173,174]. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.