Biomarkers Predictive of Immunotherapy Efficacy in Head and Neck Squamous Cell Carcinoma: Current Insights and Future Perspectives

With the approval of immunotherapies by regulatory bodies, head and neck squamous cell carcinoma (HNSCC) treatment has been revolutionized, and anti-programmed cell death-1 (anti-PD-1) agents are now the standard for platinum-resistant recurrent/metastatic HNSCC. However, programmed death ligand 1 (PD-L1) expression does not always align with treatment efficacy, and given the risk of immune-related toxicities and high costs, identifying predictive biomarkers is crucial. This review comprehensively examines the current evidence for diverse biomarkers predictive of HNSCC response to anti-PD-1/PD-L1 therapy, including but not limited to PD-L1 expression, tumor mutational burden (TMB), features of the tumor microenvironment (TME), and circulating biomarkers. This integrative approach aims to overcome current limitations, comprehensively evaluate immunotherapy response potential, enhance prognostic assessment, and ultimately guide personalized treatment strategies in clinical practice for HNSCC patients.