Abstract 3360: Negative predictive value of circulating tumor tissue modified viral HPV DNA for identifying recurrence among patients treated for HPV-driven oropharyngeal cancer

Abstract Purpose: Despite favorable outcomes, up to 20% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will experience recurrence. Monitoring circulating tumor tissue modified viral (TTMV)-HPV DNA during post-treatment surveillance has emerged as a tool that has demonstrated >95% positive predictive value (PPV) for detecting recurrence. Here we describe a large real-world population with detailed clinical follow-up, permitting determination of the longitudinal negative predictive value (NPV) of the assay. Patients and methods: This IRB-approved, retrospective observational cohort study included 312 patients across five U.S. centers who were ≥3 months post-treatment for HPV-driven OPSCC. Patients had one or more TTMV-HPV DNA results (NavDx®, Naveris Laboratories) obtained during surveillance between February 2020 and January 2021. A baseline TTMV-HPV DNA test was not required. HPV status was assessed by p16 immunohistochemistry or HPV PCR/ISH. Test results were correlated with physician-reported exam and imaging findings to assess disease status in follow-up. Results: The cohort was mostly male (85%), had a median age of 61 (range: 27-81), included smokers (50%), and 282 (90%) had involved nodes (N1: 204, N2: 70, N3: 8) at initial staging. Curative-intent treatment involved surgery with or without another modality in 54% of cases (169/312). Median follow-up time was 23.5 months, and 39 patients (12.5%) had documented recurrence. Most patients had >1 TTMV-HPV DNA test result ≥3 months post-treatment (231, 74%), with 48 (15%) having 5 or more tests. Among patients with multiple negative surveillance tests, the median time between tests was 126 days (4.2 months, range: 0.37-24.2). The first TTMV-HPV DNA surveillance test was most often performed within the first year post-treatment (195, 63%). Across 812 test results, the NPV was 99.5%. There were 4 false negative tests among patients with confirmed p16-positive (3/4) or HPV PCR-positive (1/4) biopsy-proven recurrence. One of these patients had a subsequent positive TTMV-HPV DNA test during salvage immunotherapy. Only one of these patients had baseline TTMV-HPV DNA testing available, which showed a low positive <50 TTMV-HPV16 DNA Score, whereas the other three patients did not have a baseline result available. Conclusion: Our findings further support the clinical potential of monitoring circulating TTMV-HPV DNA during post-treatment surveillance. We demonstrate a very high assay NPV correlated with physician-reported outcomes. TTMV-HPV DNA can be used to assist in surveillance and could inform imaging needs and future practice guidelines for HPV-driven head and neck cancer survivors. Citation Format: Glenn J. Hanna, Scott Roof, James Jabalee, Eleni M. Rettig, Rocco M. Ferrandino, Sida Chen, Marshall Posner, Krzysztof J. Misiukiewicz, Eric M. Genden, Raymond L. Chai, John Sims, Elaine Thrash, Scott J. Stern, Adam Raben, Lydia I. Clements, Abie H. Mendelsohn, Charlotte Kuperwasser, Catherine Del Vecchio Fitz, Barry M. Berger. Negative predictive value of circulating tumor tissue modified viral HPV DNA for identifying recurrence among patients treated for HPV-driven oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3360.