In HPV-negative HNSCC, most frequent mutations and chromosomal alterations occurred in the driver genes P53 (84%), CDKN2A (58%), PIK3CA (34%), CCND1 (31%), EGFR (15%), MYC (14%), NOTCH1 (14%), and FGFR1 (10%) [5]. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.