The Clinical Impact of TTMV-HPV DNA in Anal Cancer Surveillance

Multicenter data show TTMV-HPV DNA clarifies indeterminate post-treatment findings in anal cancer surveillance.

A recent study finds circulating TTMV-HPV DNA reliably resolves ambiguous exams and imaging, reducing diagnostic uncertainty after treatment in patients with HPV-associated anal squamous cell carcinoma.

This multicenter retrospective evaluation included 233 patients from ten U.S. centers and captured 603 post-treatment TTMV-HPV DNA assays; 185 patients had at least one post-treatment test. Investigators prespecified concordance between TTMV-HPV DNA and near-term clinical outcomes for clinically indeterminate findings (CIFs) as the primary endpoint. The cohort generated 214 CIFs from exams and imaging, and prespecified pairing rules produced 52 evaluable CIF/TTMV-HPV DNA pairs that formed the basis for accuracy estimates.

Imaging produced CIFs in 17% of assessments and clinical exams in 7%, while TTMV-HPV DNA tests were indeterminate in just 1.3% of assays. Circulating TTMV-HPV DNA offers tumor-specific, anatomically independent information that complements physical exam and imaging, particularly when post-treatment fibrosis or edema obscure local assessment — providing a noninvasive biochemical readout to reduce interpretive ambiguity.

Among the 185 patients with post-treatment testing, 21 (11%) had at least one positive TTMV-HPV DNA result and 30 positive tests were recorded overall. Positive assays were often the first indicator of recurrence and, where follow-up was sufficient, recurrence was subsequently confirmed in all evaluable patients. In CIF-associated analyses, every positive TTMV-HPV DNA result (11/11) was concordant with clinically confirmed recurrence, indicating that positive detection by the assay accurately signaled active disease in this series.

Of 52 evaluable CIF/TTMV-HPV DNA pairs, the assay correctly predicted disease status in 48/52 pairs (92%, 95% CI: 82–98). Negative tests were concordant with no recurrence in 37/41 cases (90%), and positive tests were concordant with recurrence in 11/11 cases (100%). TTMV-HPV DNA preceded clinical confirmation of recurrence in 73% of positive CIF-associated cases, with a median lead time to clinical detection of 29 days (IQR 19–129), showing the test frequently shortens the window of diagnostic uncertainty.