Clinical validity of TTMV-HPV DNA liquid biopsies for the diagnosis and surveillance of HPV-associated oropharyngeal carcinoma.

person Scott A. Roof Icahn School of Medicine at Mount Sinai, New York, NY info_outline Scott A. Roof, Rocco Ferrandino, Sida Chen, Catharine Kappauf, Joshua Barlow, Brandon Gold, William Westra, Michael Berger, Marita S Teng, Mohemmed N Khan, Richard Lorne Bakst, Kunal K. Sindhu, Eric Michael Genden, Raymond L Chai, Marshall R. Posner, Krzysztof Misiukiewicz

Authors person Scott A. Roof Icahn School of Medicine at Mount Sinai, New York, NY info_outline Scott A. Roof, Rocco Ferrandino, Sida Chen, Catharine Kappauf, Joshua Barlow, Brandon Gold, William Westra, Michael Berger, Marita S Teng, Mohemmed N Khan, Richard Lorne Bakst, Kunal K. Sindhu, Eric Michael Genden, Raymond L Chai, Marshall R. Posner, Krzysztof Misiukiewicz Organizations Icahn School of Medicine at Mount Sinai, New York, NY, Icahn School of Medicine Department of Pathology, New York, NY, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, Icahn School of Medicine, New York, NY, Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, Mount Sinai Hospital, New York, NY Abstract Disclosures Research Funding No funding received None. Background: While there are several HPV biomarker assays, a commercially available assay evaluating tumor tissue modified viral DNA (TTMV-HPV DNA) (NavDx, Naveris Inc, Natick, MA) has shown impressive results in clinical trials and small cohort studies. Our aim was to establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary, real-world clinical setting. Methods: In this retrospective analysis, we evaluated the accuracy of the TTMV-HPV DNA assay in detecting HPVOPSCC in the diagnostic (pre-treatment) and surveillance phases of care between April 2020 and October 2022. For the diagnostic cohort, patients with OPSCC and at least one TTMV-HPV DNA measurement prior to initiation of primary therapy were included in the analysis. For the surveillance cohort, all TTMV-HPV DNA tests performed 3 months after completion of primary therapy for pathologically confirmed HPV-associated OPSCC were evaluated, regardless of pre-treatment TTMV-HPV DNA testing. Patients with suspected recurrence, but without pathologic confirmation, were excluded. HPV status was defined utilizing positive p16 staining on immunohistochemistry (93.2% diagnosis; 97.9% surveillance) or HPV polymerase chain reaction/in situ hybridization (79.6% diagnosis; 89.7% surveillance). Results: In the diagnostic cohort, 163 patients were included. The cohort included mostly men (87%) with median age 63, of which 93.3% had HPVOPSCC versus 6.7% had HPV negative OPSCC. The sensitivity in pre-treatment diagnosis was 91.5%; its specificity was 100%. In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. 23 patients had pathologically confirmed recurrences. The assay demonstrated 79.2% sensitivity and 100% specificity in detecting the recurrences. Positive predictive value was 100% and negative predictive value was 98.2%. The median lead time from positive test to pathologic confirmation was 28 days, 6/18 (30%) had lead time >50 days (maximum 507 days). Conclusions: The commercially available NavDx TTMV-HPV DNA assay demonstrated 100% specificity, and therefore excellent positive predictive value, in both diagnosis and surveillance. However, the sensitivity was lower, 91.5% for the diagnosis cohort and 79.2% for the surveillance cohort, signifying that a negative value may require further work-up. Further studies will be required to determine the optimal timing of testing and how results should inform treatment decisions. 2x2 Tables for diagnosis (A) and surveillance (B) cohorts. A) Diagnosis Cohort (n = 163) B) Surveillance Cohort (n = 591 # ) TTMV-HPV DNA HPV+ OPSCC HPV- OPSCC Recurrence Disease Free Positive 139 0 38 0 Negative 13 11 10 543 #Surveillance cohort analysis performed at the test level; individual patients may have multiple tests.