Based on TCGA database, we identified that TP53 (69%), TTN (37%), FAT1 (21%), CDKN2A (20%), CSMD3 (18%), MUC16 (17%), NOTCH1 (17%), PIK3CA (17%), SYNE1 (16%) and LRP1B (15%) are the top 10 most frequently mutated genes in the HPV (−) HNSCC cohort (Fig. 1A). The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.