Data from The Cancer Genome Atlas (TCGA) indicated that PIK3CA was the most commonly mutated oncogene in HPV-positive HNSCC, while genomic alterations in HPV-negative HNSCC were mostly limited to tumor suppressor genes, including TP53, NOTCH1 and FAT1 mutations and CDKN2A inactivation [63,64,65]. Here, NOTCH1 is linked to head and neck squamous cell carcinoma.