Even beyond expected differences associated with CDKN2A and TP53, 20 genetic events were significantly more prevalent in HPV– HNSCC, including SNVs in FAT1, NOTCH1, CASP8, HRAS, the −3p highly prevalent in HPV– HNSCC and 15 other arm-level somatic copy number alterations (Supplementary Tables 1 and 2; Fisher’s exact test with Benjamini–Hochberg false discovery rate q value of <0.1). Here, CDKN2A is linked to head and neck squamous cell carcinoma.