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 (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 multicentre, prospective study enrolling 85 patients across all disease stages and 28 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 an area under the curve of 0.705. Higher ccfDNA levels were observed in early-stage HNSCC patients. While ccfDNA levels correlated with age, no significant associations were found with tumour 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 demonstrates the potential value of fluorometric ccfDNA quantification as a diagnostic, prognostic and monitoring biomarker for HNSCC. However, further well-designed studies must be carried out to enhance the clinical utility of ccfDNA as a biomarker for HNSCC management.