Tumor Biomarkers in Head and Neck Squamous Cell Carcinoma: From Etiology and Pathogenesis to Treatment Response—A Scoping Review

Currently, the global incidence of head and neck squamous cell carcinoma (HNSCC) continues to increase, with a large proportion of cases being diagnosed at advanced stages. Conventional oncological treatments are often associated with poor quality of life, while the aggressive biological behavior of these tumors results in recurrence in approximately half of treated patients according to current evidence. The need for rapid, targeted diagnosis and personalized treatment has driven research toward the identification of tumor biomarkers with diagnostic, prognostic, and predictive value for treatment response. In this scoping review, we performed a comprehensive literature search to map the available evidence on tumor biomarkers in HNSCC. We identified a wide range of biomarkers, several of which exhibit overlapping roles, and classified them according to their genomic, proteomic, cytokine-related, tumor microenvironment, metabolic, and microbiota-associated characteristics. This scoping review also summarizes the current evidence regarding biomarkers involved in carcinogenesis, treatment response and therapy resistance, while highlighting their current level of clinical applicability. Although only a limited number of biomarkers have currently been implemented in routine clinical practice in head and neck cancers, the studies included in this review identified several promising candidates with the potential to be incorporated into clinical practice following further prospective validation and methodological standardization. Many additional biomarkers are still under investigation, opening new perspectives for future diagnostic and therapeutic targets and supporting the development of personalized multimodal treatment strategies for patients with HNSCC.