In the large-scale study of genomic characterization of head neck squamous cell carcinoma (HNSCC) by The Cancer Genome Atlas Network, the major alterations are inactivating mutations of tumor suppressor genes, TP53 mutation (84%) and CDKN2A mutation or deletion (58%) in HPV negative HNSCC cases [7]. The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.