HNSCC tumors with a low T-cell inflamed phenotype (TCIP-L) were enriched in the WNT/β-catenin and Hedgehog signaling pathways, had frequent NSD1 mutations, EGFR, YAP1 amplifications and CDKN2A deletions. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.