In HNSCC, the PI3K-AKT pathway is upregulated in over 90% of cases through mechanisms including epidermal growth factor receptor activation, PI3K overexpression, phosphatase and tensin homolog mutations, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations or amplifications [17]. Here, PIK3CA is linked to head and neck squamous cell carcinoma.