Abstract
Head and neck squamous cell carcinoma (HNSCC) is a widespread malignancy and has high morbidity and mortality rates. Identifying reliable biomarkers can help in improvement of diagnosis, prognosis, and treatment response. This systematic review aimed to evaluate the diagnostic potential of various novel biomarkers against HNSCC. A comprehensive search was taken place using PubMed, Scopus, Web of Science, and Google scholar that covered range of studies published from 2019 to 2025. The search focused on biomarkers that related to HNSCC and its correlation with clinical outcomes such as survival rates and treatment response. Studies were selected on the basis of predefined eligibility criteria and included observational and experimental study designs. Data extraction was performed by two independent reviewers. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool for respective study designs. The quality of the evidence was evaluated using the GRADE approach. A total of 12 studies were included in this review after full screening process. The studies evaluated several biomarkers that indicated towards significant correlations between certain biomarkers and HNSCC prognosis. Elevated levels of expression of specific biomarkers were associated with poor survival outcomes, while others showed promise in the prediction of recurrence and treatment efficacy. The review highlighted the effectiveness of novel biomarkers for improving the HNSCC management. However, further validation of these findings and establish biomarkers for clinical use.