Programmed Cell Death Ligand 1 Expression on Immune Cells and Survival in Patients With Nonmetastatic Head and Neck Cancer: A Systematic Review and Meta-analysis

IMPORTANCE: The failure or success of radical treatment in patients with head and neck squamous cell carcinoma (HNSCC) is associated with many known and unknown factors; hence, there is a search for further prognostic markers to help optimize therapeutic strategy and improve treatment outcomes. OBJECTIVE: To assess the association of programmed cell death ligand 1 (PD-L1) expression on immune or tumor cells, including its composite expression on both cell types, with overall survival (OS) or specific survival. DATA SOURCES: MEDLINE, Embase, PQSciTech, and HCAPlus databases were systematically searched for cohort studies focused on the prognostic role of PD-L1 expression in patients with HNSCC in curative stages of the disease. Search results generated publications from January 1, 2010, to January 6, 2023. STUDY SELECTION: Of 3825 publications identified, a total of 17 cohort studies in the English language met inclusion criteria of this systematic review and meta-analysis. Eligible studies reported adjusted hazard ratios (aHRs) with 95% CIs for the association of PD-L1 expression levels with OS and arbitrary specific survival. DATA EXTRACTION AND SYNTHESIS: Data from studies were extracted independently by 2 researchers strictly adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines and recommendations. The risk of bias was assessed using the Quality in Prognosis Studies tool and Newcastle-Ottawa Scale. Pooled effect estimates were obtained using a random-effect or fixed-effect model based on homogeneity of studies. MAIN OUTCOMES AND MEASURES: The primary outcome was to investigate whether there was an association between PD-L1 expression on immune or tumor cells and OS. RESULTS: In 17 cohort studies of the association of PD-L1 expression with survival in 3190 patients with HNSCC, high PD-L1 expression on immune cells was associated with a favorable OS (pooled aHR, 0.39; 95% CI, 0.25-0.59). There was no association between composite PD-L1 expression on immune and tumor cells and OS (pooled aHR, 0.79; 95% CI, 0.55-1.14) or between PD-L1 expressed only on tumor cells and OS (pooled aHR, 1.22; 95% CI, 0.87-1.70). A high level of PD-L1 expression on immune cells was associated with favorable specific survival (pooled aHR, 0.52; 95% CI, 0.38-0.72). There were no interactions between tumor location or type of primary treatment (ie, surgery vs radiotherapy or radiochemotherapy) and the association between PD-L1 expression and OS. CONCLUSIONS AND RELEVANCE: This study’s findings suggest that PD-L1 expression on immune cells may serve as a new prognostic biomarker in patients with HNSCC. However, future studies may be warranted to verify this potential role given the limited number of studies on this topic conducted and published to date.