Genetic and epigenetic alterations inactivating CDKN2A are frequently encountered in a myriad of cancers, with base sequence-altering events more common in cancer types such as melanoma, head and neck squamous cell carcinoma (HNSCC), pancreatic cancer, lung cancer, esophageal cancer, and glioblastoma multiforme (GBM) [1–3]. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.