The regulation of the cell cycle is often altered in neoplastic cells to overcome growth arrest or cellular senescence and to attain unlimited replicative potential.21 Mutation of tumor suppressor gene, TP53, is one of the earliest identified and most common genetic alterations discovered in over 50% HNSCC specimens examined.8,22 In p53 wild-type HNSCC tumors, the p53 functional pathway may be deactivated by other mechanisms, such as an increase in expression of MDM2, a negative regulator of p53, or deletion of CDKN2A, which can block p14/ARK, a suppressor of MDM2. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.