Immune checkpoint inhibitors (ICIs) such as pembrolizumab target the programmed death-1/-ligand 1 (PD-1/PD-L1) axis and have demonstrated activity in head and neck squamous cell carcinoma (HNSCC), where the seminal KEYNOTE-048 trial established the role of pembrolizumab in the first-line treatment of recurrent/metastatic HNSCC (20). This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.