IDO was strongly expressed in HPV+ vs HPV− HNSCC (P = .001). Its expression correlated with E7 HPV antigen expression (R2 = 0.84, P = .033). Combined inhibition of PD‐1 and IDO‐1 can sensitise HPV+HNSCCs to CD8+ cytotoxic T‐lymphocyte‐mediated cytotoxicity. This evidence concerns the gene CD8A and head and neck squamous cell carcinoma.