The effects of PD-1/PD-L1 checkpoint inhibitors on recurrent/metastatic head and neck squamous cell carcinoma: a critical review of the literature and meta-analysis

50% of patients with locally advanced HNSCC eventually present with disease recurrence or metastasis. Interaction of programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), allows tumour cells to evade immune attack by inhibiting T-cell activation. PD-1/PD-L1 checkpoint inhibitors block this immunosuppressive effect. This study aims to investigate the efficacy of anti-PD-1/PD-L1 agents for recurrent/metastatic (R/M) HNSCC in terms of survival, toxicity, and response. It will test the hypothesis that immunotherapy improves treatment outcomes for R/M HNSCC patients. Studies were identified through an electronic search of databases EMBASE and Medline. Data on survival, response and toxicity following PD-1/PD-L1 inhibition was extracted from included studies and compared. A subgroup meta-analysis compared these outcomes in PD-1/PD-L1 inhibition versus the standard of care (SOC). Thirteen studies (<i>n</i> = 1798) were included in this review. Overall survival following PD-1/PD-L1 checkpoint inhibition ranged from 6 to 13 months. The most common treatment-related adverse events (TRAEs) were fatigue, hypothyroidism and nausea; Grade ≥3 TRAEs occurred in 13% of patients. Meta-analysis of RCTs showed that anti-PD-1/PD-L1 agents improved survival and reduced toxicity compared to the SOC. This was demonstrated by a 37% lower risk of death (OR = 0.63, 95% CI = 0.51–0.78, <i>I</i>² = 18%, <i>p ≤</i> 0.0001) and a 77% lower risk of any-grade TRAEs (OR = 0.23, 95% CI = 0.18–0.29, <i>I</i>² = 90%, <i>p ≤</i> 0.00001) with immunotherapy versus SOC. Based on the observed safety and efficacy, PD-1/PD-L1 checkpoint inhibition improves treatment outcomes for R/M HNSCC patients. PD-1/PD-L1 inhibitors significantly prolonged survival and reduced toxicity compared to the SOC, however further randomised trials are needed to investigate their role in HNSCC.