NOTCH1 and head and neck squamous cell carcinoma: These studies have shown that non-viral HNSCC is broadly driven by non-mutually exclusive mutations in genes involved in four pathways: cell survival and proliferation (TP53, EGFR, PIK3CA, and HRAS), cell-cycle control (CDKN2A and CCND1), cellular differentiation (NOTCH1), and cellular adhesion and invasion signaling (FAT1) [31,48,49].