p16INK4a is a tumor suppressor protein. It is a specificinhibitor of cdk4/cdk6, and a tumorsuppressor involved inthe pathogenesis of a variety of malignancies. Recentanalyses of the p16INK4a gene revealed homozygousdeletions, nonsense, missense, or frameshift mutations inseveral human cancers. Although the frequency of p16INK4aabnormalities is higher in tumor derived cell lines than inunselected primary tumors, significant subsets of clinicalcases with aberrant p16INK4a gene have been reportedamong melanomas, gliomas, esophageal, pancreatic, lung,and urinary bladdercarcinomas, and some types of leukemia.Expression of p16INK4a (p16 positive) is highly correlatedwith human papilloma virus (HPV) infection in head and necksquamous cell carcinomas (HNSCC). p16 status is animportant prognostic indicator in HNSCC and the p16positive/HPV16 negative group is likely a distinct subgrouplacking any HPV genotype.