Circulating Cell-free DNA Concentration as a Biomarker in Head and Neck Cancer

Abstract

Objective: Head and neck squamous cell carcinoma (HNSCC), particularly human papillomavirus virus (HPV) -negative HNSCC, poses a significant clinical challenge due to late diagnoses and poor survival. This study evaluates the potential of circulating cell-free DNA (ccfDNA) as a minimally invasive biomarker for diagnosis, prognosis, and disease monitoring in HNSCC. Methods: We conducted a multicenter, prospective study enrolling patients across all disease stages and healthy controls, using two quantification ccfDNA methods: fluorometry (Qubit) and quantitative real-time polymerase chain reaction (qPCR). Results: Baseline plasma ccfDNA concentrations were significantly elevated in HNSCC patients compared to healthy controls, with a diagnostic accuracy of 70.5%. Higher ccfDNA levels were observed in early-stage HNSCC patients. While ccfDNA levels correlated with age, no significant associations were found with tumor stage or location. Patients with lower post-treatment ccfDNA levels demonstrated longer median progression-free survival (PFS) (16.37 months vs. 9.63 months, p<0.05). Longitudinal analysis of locally advanced HNSCC revealed significant inter-patient variability in ccfDNA kinetics. Conclusions: Our study provides evidence of the potential value of fluorometric ccfDNA quantification as a diagnostic, prognostic and monitoring biomarker for HNSCC. However, further well-design studies must be carried out to enhance the clinical utility of ccfDNA as biomarker for HNSCC management.