The response rates of a clinical trial including 172 pembrolizumab-treated head and neck squamous cell carcinoma (HNSCC) patients with recurrent or metastatic disease were 23.0% (95% CI, 16.0–31.4) and 26.6% (95% CI, 18.0–36.7) in PD-L1- and PD-L2- positive patients, respectively. This evidence concerns the gene PDCD1LG2 and head and neck squamous cell carcinoma.