Evaluation of integrated hpv dna as individualized biomarkers for the detection of recurrent cin2/3 during post-treatment surveillance

Hoyer H, Mehlhorn G, Scheungraber C, Hagemann I, Hirchenhain C, Woelber L, Stolte C, Hampl M, Scherbring S, Denecke A, Bartels J, Ebert AD, Meneder S, Petzold A, Heller T, Heidtke KR, Schwarz E, Stübs F, Schütze S, Stange EL, Jaeger A, Martignoni F, Dellmann A, Rody A, Hillemanns P, Fehm T, Petry KU, Böhmer G, Schmalfeldt B, Wimberger P, Beckmann M, Runnebaum IB, Dürst M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cancers MDPI

Book Volume: 13

Article Number: 3309

Journal Issue: 13

DOI: 10.3390/cancers13133309

Abstract

Purpose: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. Methods: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients’ individual HPV-integration sites (vcj-PCR on the basis of NGS). Results: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6–34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8–27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7–20.7%) and predicted ten of fourteen recurrences at six months. Conclusions: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

Authors with CRIS profile

Frederik Stübs Department of Obstetrics and Gynaecology Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde

Involved external institutions

Universitätsklinikum Jena DE Germany (DE) Universitätsklinikum Düsseldorf DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Klinikum Wolfsburg DE Germany (DE) abts+partner Partnerschaftsgesellschaft DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Städtisches Klinikum Braunschweig DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Technische Universität Dresden DE Germany (DE) ATLAS Biolabs GmbH DE Germany (DE)

How to cite

APA:

Hoyer, H., Mehlhorn, G., Scheungraber, C., Hagemann, I., Hirchenhain, C., Woelber, L.,... Dürst, M. (2021). Evaluation of integrated hpv dna as individualized biomarkers for the detection of recurrent cin2/3 during post-treatment surveillance. Cancers, 13(13). https://doi.org/10.3390/cancers13133309

MLA:

Hoyer, Heike, et al. "Evaluation of integrated hpv dna as individualized biomarkers for the detection of recurrent cin2/3 during post-treatment surveillance." Cancers 13.13 (2021).

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