The Promise of Circulating Tumor DNA in Head and Neck Cancer

SIMPLE SUMMARY: Head and neck cancer remains a challenging and deadly disease as it is often identified in more advanced stages due to limitations in screening and surveillance. Circulating tumor DNA (ctDNA) has the potential to improve outcomes by enhancing screening, early diagnosis, and surveillance in head and neck cancer patients. In this review, we discuss the current state of the literature using ctDNA as a biomarker for head and neck cancer screening, diagnosis, treatment response, and prognosis. ABSTRACT: As the seventh most common cancer globally, head and neck cancers (HNC) exert considerable disease burden, with an estimated 277,597 deaths worldwide in 2020 alone. Traditional risk factors for HNC include tobacco, alcohol, and betel nut; more recently, human papillomavirus has emerged as a distinct driver of disease. Currently, limitations of cancer screening and surveillance methods often lead to identifying HNC in more advanced stages, with associated poor outcomes. Liquid biopsies, in particular circulating tumor DNA (ctDNA), offer the potential for enhancing screening, early diagnosis, and surveillance in HNC patients, with potential improvements in HNC patient outcomes. In this review, we examine current methodologies for detecting ctDNA and highlight current research illustrating viral and non-viral ctDNA biomarker utilities in HNC screening, diagnosis, treatment response, and prognosis. We also summarize current challenges and future directions for ctDNA testing in HNC patients.