Circulating Tumor DNA: Reducing Burden in HPV+ Oropharyngeal Cancer Surveillance

This review examines the rising prevalence of human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) and evaluates the role of circulating tumor HPV DNA (ctHPVDNA) in diagnosis and post-treatment surveillance. A comprehensive literature search of electronic databases, including PubMed, Medline, Cochrane Library, and Google Scholar, identified studies that validated ctHPVDNA as a biomarker with high sensitivity and specificity, assessed its cost-effectiveness, and explored patient and provider perceptions. Clinical evidence supports that plasma-based ctHPVDNA is the most accurate method for detecting disease recurrence and quantifying tumor burden. Patient perception studies reported high confidence in ctHPVDNA testing, while providers viewed it as broadly beneficial, advocating for judicious utilization and further investigation into false negative results. Limitations included variability in test sensitivity for specific patients and the need for standardization of testing intervals. Ultimately, ctHPVDNA shows promise to supplement or replace current surveillance methods, which rely heavily on costly imaging and exams. Incorporating ctHPVDNA into routine surveillance could enhance early recurrence detection, expand access to care in rural populations, promote health equity, and reduce the economic burden of HPV+ OPSCC care.