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.