This region includes tumor suppressor genes, CDKN2A which encodes for CDK4 and CDK6 inhibitor p16INK4A and ARF encoding p14 which is a stabilizer of p53. The accumulation of altered key tumor suppressor genes such as TP53 and CDKN2A, which encode p53 and p16INK4A, respectively is associated with the onset, progression and poor prognosis of HPV-negative HNSCC. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.