Today, the two programmed cell death protein 1 (PD-1) inhibitors nivolumab and pembrolizumab are approved for patients with recurrent or metastatic HNSCC and pembrolizumab alone or in combination with platinum and fluorouracil is the SOC for the first-line treatment in patients with PD-L1 positive tumors. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.