Tissue and Blood-Based Tumor Mutational Burden Predicts Treatment Response to PD-1 Blockade in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Tumor mutational burden (TMB) is a predictive biomarker for immune checkpoint inhibitors (ICIs). Its clinical utility in head and neck squamous cell carcinoma (HNSCC) is limited by differences in detection approaches and inconsistent cut-off values. In this meta-analysis, we systematically reviewed multiple high-quality studies to assess the predictive value of tissue-based TMB (tTMB) and blood-based TMB (bTMB) for treatment response of ICIs.

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed, Web of Science, Scopus, and SpringerLink for studies published through January 2026. Eligible studies included HNSCC patients treated with ICIs, with outcomes stratified by TMB status. The primary endpoint was objective response rate (ORR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS).

In addition, subgroup analyses were conducted to further explore between-study differences according to different TMB detection approaches. We included 17 independent high-quality cohorts comprising 1472 patients. High TMB was evaluated using two approaches: tTMB and bTMB, and this two-modality framework was consistently applied to survival outcomes. Overall, high TMB showed prognostic utility across both tissue and blood measurements.

Specifically, high TMB was associated with improved ORR (odds ratio [OR] = 2.80; 95% CI, 2.14-3.65; p