Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: Treatment de-escalation has been increasingly studied as a strategy to reduce treatment toxicity without compromising favorable disease prognosis in patients with HPV-positive oropharyngeal cancer. Circulating tumor DNA (ctDNA) has emerged as a potential non-invasive tool to help guide treatment decision-making and detect cancer recurrence. This study investigates the association between ctDNA clearance at various timepoints during and after treatment with clinicopathological characteristics and disease outcomes.
Methods: This was a single-institution retrospective study of HPV-associated OPSCC patients with available pre- and post-treatment ctDNA testing between April 2020 and September 2024. Differences in clinical and pathological features, recurrence rates, and survival were compared in patients with negative and positive ctDNA results after total treatment completion (Cohort 1) and after initial surgery (Cohort 2).
Results: Cohort 1 included 119 patients, with 53 receiving non-surgical treatment, 48 receiving surgery alone, and 18 receiving surgery with adjuvant treatment. 96.6% (115/119) of patients in Cohort 1 demonstrated post-treatment TTMV-HPV DNA clearance. Amongst surgically treated patients, more than 25% patients with negative post-treatment TTMV-HPV DNA had adverse features on surgical pathology. Of the four patients with post-treatment positive TTMV-HPV DNA, three demonstrated persistent disease or recurrence. One patient, who had been treated non-surgically, demonstrated clearance of TTMV at the subsequent surveillance visit and remains disease free. Nearly 10% of post-treatment negative patients had recurrence, despite absence of detectable plasma HPV DNA at time of treatment completion. All recurrences with associated TTMV-HPV DNA testing were positive (10/11) or indeterminate (1/11) at time of clinical detection of recurrence. There was a trend towards shorter time-to-recurrence in patients with positive post-treatment TTMV-HPV DNA. Post-operative TTMV-HPV DNA results in Cohort 2 reflected similar findings.
Conclusion: While ctDNA testing may serve as a promising non-invasive tool for disease surveillance in HPV-associated OPSCC, with detectable ctDNA levels prompting evaluation for recurrence, the utility of post-operative and post-treatment ctDNA clearance is less established. The findings of this study suggest there is a threshold of minimal residual disease detection, below which true disease status may not be accurately classified. As such, ctDNA clearance alone should not yet be considered a reliable biomarker for treatment decision-making, particularly in adaptive treatment settings outside of a clinical trial.