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Hoyer, Heike; Mehlhorn, Grit; Scheungraber, Cornelia; Hagemann, Ingke; Hirchenhain, Christine; Woelber, Linn; Stolte, Claudia; Hampl, Monika; Scherbring, Sarah; Denecke, Agnieszka; Bartels, Janina; Ebert, Andreas D.; Meneder, Sabina; Petzold, Annett; Heller, Tabitha; Heidtke, Karsten R.; Schwarz, Elisabeth; Stübs, Frederik; Schütze, Stefanie; Stange, Eva-Lena; Jaeger, Anna; Martignoni, Franca; Dellmann, Ansgar; Rody, Achim; [...]

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance

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  • Medientyp: E-Artikel
  • Titel: Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance
  • Beteiligte: Hoyer, Heike; Mehlhorn, Grit; Scheungraber, Cornelia; Hagemann, Ingke; Hirchenhain, Christine; Woelber, Linn; Stolte, Claudia; Hampl, Monika; Scherbring, Sarah; Denecke, Agnieszka; Bartels, Janina; Ebert, Andreas D.; Meneder, Sabina; Petzold, Annett; Heller, Tabitha; Heidtke, Karsten R.; Schwarz, Elisabeth; Stübs, Frederik; Schütze, Stefanie; Stange, Eva-Lena; Jaeger, Anna; Martignoni, Franca; Dellmann, Ansgar; Rody, Achim; [...]
  • Erschienen: MDPI AG, 2021
  • Erschienen in: Cancers
  • Sprache: Englisch
  • DOI: 10.3390/cancers13133309
  • ISSN: 2072-6694
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>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.</jats:p>
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