In HPV-negative SCCHN, alteration of the tumor suppressor genes Tumor protein 53 (TP53) and Cyclin-dependent kinase inhibitor 2A (CDKN2A) (occurring in 84% and 58% of cases, respectively), and the amplification of the proto-oncogenes Cyclin D1 (CCND1) and Myelocytomatosis viral related oncogene (MYC) (occurring in 31% and 14% of cases, respectively) results in the activation of cyclin-dependent kinase (CDK) 4/6-CylinD complexes leading to cell cycle progression [17,18,19]. Here, TP53 is linked to head and neck squamous cell carcinoma.