In HNSCC, PI3K/AKT/mTOR signaling is active in more than 90% of HNSCC as a result of EGFR activation, PI3K overexpression, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) mutations/amplifications, and PTEN mutation (116, 134). Here, PTEN is linked to head and neck squamous cell carcinoma.