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Abstract

Oropharyngeal squamous cell carcinoma (OPSCC) is a malignancy of the tonsil, base of tongue, and pharyngeal wall, with a rising incidence among younger individuals with human papillomavirus (HPV)-associated disease. Despite advances in treatment, early detection and surveillance remain limited. We evaluate the clinical utility of a circulating blood-based microRNA (miRNA) biomarker for early detection and monitoring of OPSCC. To develop the OCSCC biomarker, serum was collected from patients and healthy controls, and RNA extracted and profiled using reverse-transcription quantitative PCR (RT-qPCR). A two-miRNA classifier was identified, which was applied to OPSCC samples. The classifier distinguished OPSCC from controls with high discriminatory ability. To assess its longitudinal performance, pre- and post-treatment and serial samples were compared. Scores decreased prior to clinical recurrence indicating responsiveness to tumour burden and remained above the threshold in nonrecurrent cases. Score dynamics varied by treatment modality, suggesting potential interaction with therapeutic context. These findings support the feasibility of a circulating miRNA classifier for both detection and treatment monitoring in OPSCC. While larger, prospective studies are needed to confirm clinical utility, this work establishes a foundation for non-invasive biomarker-driven surveillance in head and neck oncology.