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

Ana María Rodríguez-Ces ^1,2,3, Óscar Rapado-González ^1,3,4,5,6, Santiago Aguín-Losada ^7,8

¹Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
²Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
³Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela Foundation (FIDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.
⁴Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
⁵Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal.
⁶Medical Devices Research Group, International Iberian Nanotechnology Laboratory (INL), Braga, Portugal.
⁷Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela Foundation (FIDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.
⁸Department of Medical Oncology, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain.
⁹Department of Radiation Oncology, Hospital Universitario Lucus Augusti (HULA, SERGAS), Lugo, Spain.
¹⁰Oral and Maxillofacial Surgery Department, Complexo Hospitalario Universitario de A Coruña (CHUAC, SERGAS), A Coruña, Spain.
¹¹Department of Radiation Oncology, Centro Oncológico de Galicia (COG), A Coruña, Spain.

⁰Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.

Oral Diseases +

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June 27, 2025

View abstract on PubMed

Summary

Circulating cell-free DNA (ccfDNA) shows promise as a biomarker for diagnosing and monitoring head and neck squamous cell carcinoma (HNSCC). Lower post-treatment ccfDNA levels correlate with improved progression-free survival in HNSCC patients.

Area Of Science

Oncology
Molecular Diagnostics
Biomarker Discovery

Background

Head and neck squamous cell carcinoma (HNSCC), especially human papillomavirus (HPV)-negative types, presents diagnostic and survival challenges.
Early detection and effective monitoring are crucial for improving patient outcomes in HNSCC.

Purpose Of The Study

To evaluate circulating cell-free DNA (ccfDNA) as a minimally invasive biomarker for HNSCC diagnosis, prognosis, and disease monitoring.
To compare fluorometry and quantitative real-time polymerase chain reaction (qPCR) for ccfDNA quantification.

Main Methods

A prospective, multicentre study involving 85 HNSCC patients and 28 healthy controls.
Quantification of plasma ccfDNA using fluorometry (Qubit) and qPCR.
Analysis of baseline and post-treatment ccfDNA levels, correlating with clinical data.

Main Results

Plasma ccfDNA was significantly elevated in HNSCC patients (AUC 0.705), with higher levels in early stages.
Lower post-treatment ccfDNA levels were associated with longer progression-free survival (PFS) (16.37 vs. 9.63 months).
ccfDNA levels correlated with age but not tumor stage or location; longitudinal kinetics showed inter-patient variability.

Conclusions

Fluorometric quantification of ccfDNA holds potential as a diagnostic, prognostic, and monitoring biomarker for HNSCC.
Further research is needed to optimize ccfDNA's clinical utility in HNSCC management.

Keywords:

biomarker cell‐free DNA diagnostic head and neck cancer quantification