PD-L1 immunohistochemistry has demonstrated some value in identifying responders to anti-PD-1 treatment; in fact, single-agent pembrolizumab is indicated as a first-line, single-agent therapy for R/M HNSCC patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 1 [7,8]. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.