Circulating Tumor DNA in Head and Neck Cancer

Importance: Despite gains in understanding head and neck cancer over the past several decades, the discovery of reliable biomarkers remains elusive. With the advent of human papillomavirus-associated oropharynx cancer and Epstein-Barr virus-associated nasopharynx cancer, circulating tumor DNA (ctDNA) and oncogenic viral DNA have emerged as potentially promising biomarkers. Observations: A review was conducted by the American Head and Neck Society to address the current utility of ctDNA. Ongoing clinical trials were reviewed, with discussion of its utility in monitoring treatment response and measuring minimal residual disease (MRD). Although ctDNA holds promise in the push for precision oncology, several questions remain regarding its routine clinical use, including test variability and implications of inaccurate test results. Optimized clinical trial designs and further research are necessary to bring ctDNA to the forefront of head and neck cancer management. Conclusions and Relevance: Liquid biopsy targeting viral ctDNA is a promising biomarker in the diagnostic and surveillance settings across head and neck cancer types. Ongoing clinical trials will help elucidate how ctDNA can be implemented to monitor treatment response, assess MRD, and frame treatment decisions to adapt treatment via a precision oncology approach.