RT Journal Article T1 Circulating Cell-free DNA Concentration as a Biomarker in Head and Neck Cancer T2 Cell-free DNA as a Biomarker in Head and Neck Cancer A1 Rodríguez Ces, Ana María A1 Rapado González, Óscar A1 Aguín Losada, Santiago A1 Formoso García, Inés A1 López Cedrún, José Luis A1 Triana Martínez, Gabriel A1 López López, Rafael A1 Suárez Cunqueiro, María Mercedes K1 Cell-free DNA K1 Head and neck cancer K1 Quantification K1 Diagnostic K1 Biomarker AB 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. PB Wiley YR 2025 FD 2025 LK https://hdl.handle.net/10347/39945 UL https://hdl.handle.net/10347/39945 LA eng NO This is the pre-peer reviewed version of the following article: Rodríguez-Ces, A. M., Ó. Rapado-González, S. Aguín-Losada, et al. 2025. “ Circulating Cell-Free DNA Concentration as a Biomarker in Head and Neck Cancer.” Oral Diseases 1–12, which has been published in final form at https://doi.org/10.1111/odi.70002. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. NO This research was funded by the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, grant number (PI20/01449). A.M.R.G. is funded by a Predoctoral Research Fellowship from Axencia Galega de Innovación (GAIN), Programa de Ayudas a la Etapa Predoctoral de la Xunta de Galicia (IN606A-2021/007). O.R.G. is funded by a Postdoctoral Research Fellowship from Axencia Galega de Innovación (GAIN), Programa de Ayudas a la Etapa Posdoctoral de la Xunta de Galicia (IN606B-2022/007). DS Minerva RD 24 abr 2026