Post-treatment circulating tumor DNA clinical features, prognosis in HPV-positive oropharynx cancer

Treatment de-escalation has been studied to reduce treatment toxicity in patients with HPV-associated oropharyngeal cancer(OPSCC). Circulating tumor DNA(ctDNA) is a potential non-invasive tool to assist treatment decision-making and recurrence detection. This study investigates the association between ctDNA clearance at timepoints during and after treatment with clinicopathological characteristics and outcomes.

In this retrospective cohort study conducted between April 2020-August 2025 at a tertiary care center in a large city, 132 patients treated for HPV-associated OPSCC with available pre- and post-treatment ctDNA testing were analyzed for the presence of detectable ctDNA following treatment. Main outcomes included presence of recurrence, persistent disease, and overall survival. Differences in clinical and pathological features were also recorded.

132 patients were included in the post-treatment completion cohort (non-surgical treatment:54; surgery alone:58; surgery with adjuvant treatment:20). 97.7%(129/132) of patients in this cohort demonstrated post-treatment TTMV-HPV DNA clearance. Amongst surgically treated patients, 43% patients with negative post-treatment TTMV-HPV DNA had adverse features on surgical pathology. All three patients with post-treatment positive TTMV-HPV DNA demonstrated persistent/recurrence disease. There was a significant difference in recurrence-free survival in those with positive results compared to negative. 10.9% of post-treatment negative patients experienced recurrence. There was significantly shorter time-to-recurrence in positive post-treatment TTMV-HPV DNA patients. Post-operative TTMV-HPV DNA results in the post-surgical cohort reflected similar findings.

The findings suggest there is a threshold of minimal residual disease detection, below which true disease status may not be accurately classified. CtDNA clearance alone is not yet a reliable biomarker for treatment decision-making.