Resolving Clinically Indeterminate Findings During Anal Cancer Surveillance with TTMV-HPV DNA.

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Biomarkers

Background:

• Anal squamous cell carcinoma (ASCC) surveillance relies on clinical exams and imaging.
• Post-treatment changes can lead to clinically indeterminate findings (CIFs), delaying diagnosis.
• Noninvasive biomarkers are needed to improve diagnostic accuracy.

Purpose of the Study:

• To evaluate the utility of circulating tumor tissue-modified viral (TTMV)-HPV DNA testing in clarifying CIFs during ASCC surveillance.
• To assess the accuracy and impact of TTMV-HPV DNA testing on the early detection of ASCC recurrence.

Main Methods:

• A multi-center retrospective study of 233 patients with HPV-associated ASCC.
• Analysis of 185 patients with post-treatment TTMV-HPV DNA tests, focusing on 52 CIF/TTMV-HPV DNA pairs.
• Comparison of TTMV-HPV DNA results with clinical outcomes within prespecified follow-up windows.

Main Results:

• TTMV-HPV DNA testing demonstrated a low indeterminate rate (1.3%) compared to exams (7%) and imaging (17%).
• TTMV-HPV DNA accurately resolved disease status for 92% of CIFs (48/52).
• Positive TTMV-HPV DNA tests accurately predicted recurrence (11/11), with 73% indicating recurrence earlier than standard methods.

Conclusions:

• TTMV-HPV DNA testing is a highly accurate biomarker for clarifying indeterminate findings in ASCC surveillance.
• This noninvasive test can lead to earlier detection of ASCC recurrence, improving patient management.
• Integration of TTMV-HPV DNA testing into post-treatment surveillance protocols is supported by these findings.