Only 4% of HNSCC cases exhibit mutations of mitogen-activated protein kinase (MAPK) signaling, which modulates cell proliferation, death, differentiation, angiogenesis, and dissemination.142–144 It comprises four sub-pathways, namely extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and ERK5 sub-pathways.144 In oral cancer, the ERK1/2 pathway has generated significant interest due to the fact that ERK1/2 is activated mechanistically by binding the growth factor EGF. Here, MAPK3 is linked to head and neck squamous cell carcinoma.