Diagnostic and Prognostic Significance of Chemokines in Head and Neck Cancers: A Systematic Review and Meta-Analysis

Background: Head and neck cancers (HNCs) represent a global health burden, with high morbidity and mortality largely driven by late-stage diagnosis and heterogeneous clinical outcomes. Reliable biomarkers are needed to improve early detection, prognostic stratification, and therapeutic decision-making. This study evaluates the diagnostic and prognostic value of chemokines in HNCs and identifies candidates with clinical relevance. Methods: A comprehensive literature search was conducted on 28 March 2026 across PubMed, Embase, Scopus, Web of Science, and EBSCO. Observational studies involving patients or biological samples with confirmed HNCs were included if they evaluated chemokines as diagnostic or prognostic biomarkers. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) for prognostic studies and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool for diagnostic studies. Meta-analyses were performed for chemokines evaluated in ≥3 studies using the inverse-variance heterogeneity model. Results: Forty-four studies encompassing 7294 participants were included. Prognostic findings were heterogeneous across biomarkers. MIP-3α demonstrated consistently significant associations with poorer survival outcomes. In contrast, IL-8, CXCL10, and CXCR4 showed inconsistent or predominantly non-significant associations with overall survival (OS), disease-free survival (DFS), and locoregional control (LRC). For diagnostic performance, IL-8, in saliva, demonstrated relatively high sensitivity and specificity for oral squamous cell carcinoma. Chemerin showed high diagnostic accuracy, although evidence remains limited. Conclusions: Certain chemokines show potential as diagnostic and prognostic biomarkers in HNCs. However, heterogeneity across tumor types, samples, and methodologies limits evidence. Larger, well-designed studies are needed to validate their clinical utility in risk stratification and personalized management of HNCs.