Around 80% of HNSCC cases present downregulation of p53, either via TP53 mutation (more than 50% of HPV negative HNSCC cases) or other pathways like MDM2 or cyclin dependent kinase inhibitor 1A (CDKN1A) or CDKN2A (p16), but changes in cyclin dependent kinases (CDKs), CUB and Sushi multiple domains (CSMD), nuclear factor κB (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF) genes are also described [18]. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.