The topmost frequently mutated genes in HNSCC are TP53 (72%), CDKN2A (22%), FAT1 (23%), PIK3CA (21%), NOTCH1 (19%), KMT2D (MLL2) (18%), NSD1 (10%), CASP8 (9%), AJUBA (6%), and NFE2L2 (6%). The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.