Prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma: A systematic review and comprehensive meta-analysis.

The presence of Programmed Death-Ligand 1 protein (PD-L1) in oral squamous cell carcinoma (OSCC) may indicate an ability to evade immune response and has been suggested as a prognostic marker, but there is controversy in the literature. To review the scientific evidence of a prognostic role for PD-L1 levels in OSCC. PubMed, Embase, Web of Science, and Scopus were searched for studies published on or before March 02, 2019. Studies measuring PD-L1 levels by immunohistochemistry (IHC) in OSCC were included. Study quality was assessed using the QUIPS tool. Meta-analysis was performed for survival outcomes and clinic-pathological parameters. 26 articles were included comprising 2532 patients. Analysis of studies measuring PD-L1 expression in the cell membrane showed a worse prognosis for disease-specific survival (HR = 1.74, 95% CI = 1.14-2.66, p = 0.01) and disease-free survival (HR = 1.56, 95% CI = 1.16-2.09, p = 0.003). PD-L1 overexpression was more likely in females (OR = 0.69, 95% CI = 0.53-0.91, p = 0.008), non-smokers (OR = 0.45, 95% CI = 0.27-0.75, p = 0.002), non-drinkers (OR = 0.40, 95% CI = 0.16-0.97, p = 0.04), advance stage tumours (OR = 1.63, 95% CI = 1.00-2.64, p = 0.05) and in tumours with high levels of PD-1 (OR = 33.36, 95% CI = 1.88-591.69, p = 0.02), CD4+ (OR = 3.25, 95% CI = 1.36-7.76, p = 0.008) and CD8+ (OR = 3.63 , 95% CI = 1.20-10.99, p = 0.02). This meta-analysis found a worse prognosis in OSCCs overexpressing PD-L1 in the cell membrane as measured by disease specific survival and disease-free survival. We also found positive correlations between PD-L1 overexpression and advanced tumours, females, non-smokers, non-drinkers and high levels of tumour PD-1, CD4, and CD8.

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.