Status of the PIK3CA gene was examined in 36 HPV-positive HNSCC tumors (4 CYLD-mutant, 9 TRAF3-mutant, 23 CYLD-wildtype/TRAF3-wildtype), and PIK3CA mutations tended to be mutually exclusive from CYLD/TRAF3 mutations. The gene discussed is CYLD; the disease is head and neck squamous cell carcinoma.