Liquid Biopsy in Diagnosis and Surveillance of HPV-Associated Oropharyngeal Cancer: A Systematic Review

Introduction: Circulating tumor DNA (ctDNA) has emerged as a promising tool for the detection and surveillance of HPV-positive oropharyngeal squamous cell cancer (OPSCC). The purpose of this systematic review was to study the current role of ctDNA in the diagnosis, treatment monitoring, and surveillance of HPV-associated OPSCC.

Methods: Medline (Ovid), Embase (Ovid), and Scopus were searched for original articles studying the role of liquid biopsy or ctDNA in the diagnosis or surveillance of HPV-associated oropharyngeal cancer. Two authors independently reviewed studies for inclusion and abstracted data, including study design, characterization of liquid biopsy technology, diagnostic outcomes, and risk of bias.

Results: After a preliminary screening of 440 studies, 23 studies were selected for inclusion. Of these, 10 studies were conducted retrospectively and 13 studies were conducted prospectively. Studied diagnostic tests used plasma-based droplet digital polymerase chain reaction (ddPCR, n = 13), digital PCR (dPCR, n = 3), quantitative PCR (qPCR, n = 4), or next-generation sequencing (n = 3) technology. Diagnostic accuracy outcomes were reported for pre-diagnosis (n = 1), pre-treatment (n = 18), post-treatment (n = 7), and surveillance/recurrence (n = 11) timepoints. Test sensitivities ranged from 20.6%-100% pre-treatment and 72%-100% during surveillance, while test specificities ranged from 95%-100% pre-treatment and 87.2%-100% during surveillance.

Conclusions: The majority of currently studied ctDNA technologies allow for the detection of HPV-associated OPSCC with high diagnostic accuracy. These findings support the clinical utility of ctDNA in the diagnosis, treatment monitoring, and surveillance of HPV-associated OPSCC and may facilitate earlier disease detection.