According to the observed efficacy and safety, pembrolizumab (pembro) plus platinum and 5-fluorouracil (5-FU) serves as a proper first-line therapy for R/M HNSCC while pembro monotherapy is an appropriate first-line treatment for PD-L1+ R/M HNSCC (combined positive score (CPS)>1). Here, CD274 is linked to head and neck squamous cell carcinoma.