Efficacy and safety of PD-1 inhibitors in recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.

Background: Conventional cytotoxic regimens for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) offer limited durable benefit and are associated with significant toxicity. Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have emerged as alternative treatments; however, variability in response, survival, and toxicity across studies necessitates comprehensive synthesis. This systematic review and meta-analysis evaluated the efficacy and safety of PD-1 inhibitors in adults with R/M HNSCC. Methods: A systematic search of PubMed (MEDLINE), Embase, Scopus, and Cochrane databases was conducted. Study selection followed the PICOS framework and PRISMA guidelines, with screening performed using Rayyan. Data synthesis was conducted in R (version 4.1.1) using the meta and metafor packages. The protocol was registered in PROSPERO (CRD420251169189). Results: Fourteen studies (n = 1,231) were included: nine in non-NPC HNSCC (primary analysis) and five NPC-only studies (sensitivity subgroup). In non-NPC HNSCC, pooled ORR was 22% (95% CI: 8%-48%, I Conclusion: PD-1 inhibitor combinations may be associated with higher response rates and 1-year survival compared with monotherapy in non-NPC HNSCC, at the cost of increased toxicity. These findings are hypothesis-generating and do not establish causal efficacy. Well-designed randomized trials stratified by disease subtype and treatment context are needed, alongside greater focus on quality-of-life outcomes.