Utility of Early Post‐Treatment Circulating Tumor Tissue Modified Viral HPV DNA Testing in HPV ‐Associated Oropharyngeal Cancer

BACKGROUND: TTMV-HPV DNA testing is prognostic during post-treatment surveillance of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but the significance of testing before conventional 3-month response assessment remains unclear. METHODS: We retrospectively analyzed 332 patients across 8 US sites with biopsy-proven HPV-associated OPSCC who underwent initial definitive treatment and had ≥ 1 TTMV-HPV DNA test performed 1 to 89 days after treatment completion. Event-free survival (EFS) was evaluated using a 90-day landmark approach. RESULTS: The first TTMV-HPV DNA test obtained 1-89 days after treatment was negative in 310 patients (93%), indeterminate in 3 (1%), and positive in 19 (6%). Among 59 patients with repeat testing after an initially negative result, 57 (97%) remained negative and 2 (3%) converted to positive; both patients who converted subsequently developed recurrence. Of 13 patients with an initially positive result and sufficient follow-up for trajectory analysis, 6 (46%) subsequently resolved to negative and none developed recurrence, whereas 7 (54%) remained persistently positive and 6 (86%) developed recurrence. In a 90-day landmark analysis, the last early post-treatment TTMV-HV DNA result was associated with subsequent event-free survival. CONCLUSIONS: TTMV-HPV DNA testing during the 1-89-day post-treatment interval was associated with subsequent clinical outcomes in HPV-associated OPSCC. Persistent positivity identified patients at increased risk, whereas positive results that resolved were not followed by recurrence in this cohort.