Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria; Corresponding author.
Alexander Eckert
Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
Peter Valentin Tomazic
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Axel Wolf
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Prisca Pondorfer
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Sarah Vasicek
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Matthias Graupp
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Clemens Holzmeister
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Ulrich Moser
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Alexandros Andrianakis
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Georg Kangler
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Peter Kiss
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
Luka Brcic
Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
Matthias Kappler
Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
Claudia Wickenhauser
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany
Anja Haak
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany
Maximilian Krüger
Department of Oral and Maxillofacial Surgery-Plastic Surgery, University Medical Center Mainz, Mainz, Germany
Bilal Al-Nawas
Department of Oral and Maxillofacial Surgery-Plastic Surgery, University Medical Center Mainz, Mainz, Germany
Sebastian Blatt
Department of Oral and Maxillofacial Surgery-Plastic Surgery, University Medical Center Mainz, Mainz, Germany
Norbert Brockmeyer
Department of Dermatology, Venerology, and Allergology, Center for Sexual Health and Medicine, WIR – Walk In Ruhr, Ruhr University Bochum, Bochum, Germany
Adriane Skaletz-Rorowski
Department of Dermatology, Venerology, and Allergology, Center for Sexual Health and Medicine, WIR – Walk In Ruhr, Ruhr University Bochum, Bochum, Germany
Anja Potthoff
Department of Dermatology, Venerology, and Allergology, Center for Sexual Health and Medicine, WIR – Walk In Ruhr, Ruhr University Bochum, Bochum, Germany
Lars E. French
Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany
Sara Charnowski
Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany
Markus Reinholz
Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany
Andreas M. Kaufmann
Clinic for Gynaecology, Gynaecological Tumor Immunology, Charité Campus Benjamin Franklin, Berlin, Germany
Sarah Thies
Clinic for Gynaecology, Gynaecological Tumor Immunology, Charité Campus Benjamin Franklin, Berlin, Germany
Hans-Georg Lambrecht
Bioscientia Institute for Medical Diagnostics, Ingelheim, Germany
Barbara Seliger
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany
Dominik C. Wild
Department of Otorhinolaryngology-Head&Neck Surgery, General Hospital Ried im Innkreis, Ried, Austria
Dietmar Thurnher
Department of Otorhinolaryngology-Head&Neck Surgery, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
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, 77.2–99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5–99.7%) for HPV16-induced anal cancer in HIV-positives.Overall diagnostic specificity was 99.46% for men and 99.29% for women ≥ 30 years. After vaccination, antibody 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 recurrent 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 diagnosis of tumour recurrence. An AUC of 0.96 indicates high sensitivity and specificity for early detection of HPV16-induced disease. Funding: The manufacturer provided assays free of charge.
