It is regularly altered in HNSCC, and commonly mutated in HPV-driven tumors.8,31,32 Due to the common alteration in PI3K-AKT-mTOR detected in HNSCC, several preclinical and clinical studies have attempted to target this pathway; however, the results still remain inconsistent.31,33 Pan-PI3K inhibitor buparlisib and alpha-specific PI3K inhibitor alpelisib have been widely investigated in conjunction with anti-EGFR drug cetuximab for treatment of HNSCC.34–36. This evidence concerns the gene PIK3CA and head and neck squamous cell carcinoma.