DRH1 - a novel blood-based HPV tumour marker

Weiland, Thomas; Eckert, Alexander; Tomazic, Peter Valentin; Wolf, Axel; Pondorfer, Prisca; Vasicek, Sarah; Graupp, Matthias; Holzmeister, Clemens; Moser, Ulrich; Andrianakis, Alexandros; Kangler, Georg; Kiss, Peter; Brcic, Luka; Kappler, Matthias; Wickenhauser, Claudia; Haak, Anja; Krueger, Maximilian; Al-Nawas, Bilal; Blatt, Sebastian; Brockmeyer, Norbert; Skaletz-Rorowski, Adriane; Potthoff, Anja; French, Lars E.; Charnowski, Sara; Reinholz, Markus; Kaufmann, Andreas M.; Thies, Sarah; Lambrecht, Hans-Georg; Seliger, Barbara; Wild, Dominik C. und Thurnher, Dietmar (2020): DRH1 - a novel blood-based HPV tumour marker. In: Ebiomedicine, Bd. 56, 102804

Abstract

Background: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. Methods: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression. Findings: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 772-999%) for HPV16-driven HNSCC, and 90% (95% CI, 55-5-99- 7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 9946% for men and 9929% for women >= 30 years. After vaccination, anti-body level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recur-rent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue. Interpretation: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagno-sis of tumour recurrence. An AUC of 096 indicates high sensitivity and specificity for early detection of HPV16-induced disease. (C) 2020 The Author(s). Published by Elsevier B.V.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2352-3964
• Sprache: Englisch