Over the past decade, immune checkpoint inhibitors (ICIs) against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have revolutionized the treatment of HNSCC including HPV-associated cancers with impressive anti-tumor activity and survival outcomes. This evidence concerns the gene PDCD1 and head and neck squamous cell carcinoma.