Prognostic Significance of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Tumor-Associated Neutrophils in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

OBJECTIVES

The prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and tumor-associated neutrophils (TANs) in head and neck squamous cell carcinoma (HNSCC) remains a subject of considerable research interest. This systematic review and meta-analysis aimed to evaluate the relationship between pretreatment NLR and TANs and survival outcomes in patients with HNSCC.

METHODS

The systematic literature search was conducted using PubMed, Scopus, Web of Science, and the Cochrane Library. Studies that documented pretreatment NLR in peripheral blood or TANs and their association with disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were included. Meta-analyses were performed using the R "meta" package. Subgroup analyses were performed based on tumor site and NLR thresholds. Heterogeneity was assessed using Cochran's Q and Higgins' I2 statistics, while publication bias was evaluated using Egger's test and funnel plots.

RESULTS

A total of 100 studies comprising 26 324 patients were included. The hazard ratios (HR) for OS, PFS, DFS, DSS, and RFS were 1.88, 1.95, 1.85, 2.16, and 1.11, respectively, in univariate analysis. Multivariate analysis supported these findings and showed similar trends. Subgroup analyses indicated that high NLR consistently predicted poor OS across all studied tumor sites and NLR thresholds. Elevated densities of TANs, particularly CD15+ and CXCR4+ subsets, were linked to poorer cancer-specific survival and OS, respectively.

CONCLUSION

This meta-analysis indicates that elevated pretreatment NLR, particularly above four, may serve as a significant prognostic marker of poor survival outcomes in patients with HNSCC.