This systematic review and meta-analysis of 17 cohort studies with 3190 participants of PD-L1 expression found that high PD-L1 expression levels exclusively on immune cells were associated with prolonged overall and specific survival in patients with localized and locoregionally advanced HNSCC, while PD-L1 expression on tumor cells was not associated with survival. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.