Predicting Different Recurrence Risk in <scp>HNSCC</scp> Using Circulating Inflammatory and T‐Cell Biomarkers

ABSTRACT Objective Head and neck squamous cell carcinoma (HNSCC) lacks reliable prognostic circulating biomarkers, and the role of the immune system in its progression remains incompletely understood. This study aimed to evaluate the prognostic value of systemic inflammatory and immune biomarkers in surgically treated patients with primary oral cavity (OCSCC) or laryngeal squamous cell carcinoma (LSCC). Methods This retrospective single‐center study included 394 patients with OCSCC or LSCC who underwent surgery with curative intent. Preoperative blood samples were analyzed to assess platelet, neutrophil, lymphocyte, and monocyte counts, as well as T‐cell subpopulations (CD3+, CD4+, and CD8+). Composite ratios—including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), lymphocyte‐to‐monocyte ratio (LMR), and systemic immune‐inflammation index (SII)—were evaluated for their correlation with global (GR), local (LR), and distant (DR) recurrence risk. Results Univariate analysis identified elevated platelet counts, PLR, SII, and neutrophil levels as significantly associated with increased GR ( p = 0.0001, p = 0.0014, p = 0.0058 and p = 0.016, respectively) and LR risk, with the exception of neutrophil levels ( p = 0.0002, p = 0.0008, p = 0.0072, respectively). In contrast, higher CD4+/CD3+ ( p = 0.038) and CD4+/CD8+ ( p = 0.045) ratios were associated with reduced DR risk. Multivariate analysis confirmed platelet count as an independent predictor for GR ( p = 0.0001) and LR ( p = 0.0002), while a high CD4+/CD8+ ratio ( p = 0.045) was independently protective against DR. Conclusion These findings highlight the prognostic relevance of platelet‐related inflammatory markers and circulating T‐cell ratios in recurrence risk among HNSCC patients. The differential associations with local versus distant recurrence underscore the complex interplay between systemic inflammation and adaptive immunity. Prospective validation is warranted to confirm these biomarkers' utility. Level of Evidence 4.