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2022-RA-1048-ESGO Circulating HPV cell-free DNA in cervical cancer
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  1. Suzana Mittelstadt1,
  2. Christopher Schroeder2,
  3. Olga Kelemen2,
  4. Tobias Engler1,
  5. Jakob Admard2,
  6. Axel Gschwind2,
  7. Andre Koch1,
  8. Sarah Elisabeth Wörz1,
  9. Ernst Oberlechner1,
  10. Sascha Hoffmann1,
  11. Jürgen Andress1,
  12. Felix Neis1,
  13. Bernhard Krämer1,
  14. Irina Bonzheim3,
  15. Annette Staebler3,
  16. Frank Stubenrauch4,
  17. Thomas Iftner4,
  18. Stephan Ossowski2 and
  19. Stefan Kommoss1
  1. 1Department of Women’s Health, Tübingen, Tübingen University Women’s Hospital, Tübingen, Germany
  2. 2Institute for Medical Genetics and Applied Genomics, Tübingen University Women’s Hospital, Tübingen, Germany
  3. 3Institute of Pathology and Neuropathology, Tübingen University Women’s Hospital, Tübingen, Germany
  4. 4Institute for Medical Virology and Epidemiology of Viral Disease, Tübingen University Women’s Hospital, Tübingen, Germany

Abstract

Introduction/Background Human papillomavirus (HPV) related cervical cancer is the fourth most frequent cancer in women worldwide. Currently patient follow-up and therapy monitoring is solely based on clinical examination and cross-sectional imaging. Liquid biopsies for cell-free circulating tumor DNA in cancer are a novel biomarker to detect treatment response, residual disease, and relapse. The aim of this study was to investigate the potential use of cell-free circulating HPV-DNA (cfHPV-DNA) in plasma samples of patients with cervical cancer.

Methodology In this proof-of-concept study cfHPV-DNA levels were measured using a highly sensitive Next-Generation-Sequencing-based approach targeting a panel of 13 high-risk HPV-types. For nine patients cfHPV-DNA sequencing was compared to HPV testing in corresponding paraffin embedded tumor sample. Sequential plasma samples were taken from four patients receiving primary chemoradiation.

Results A total of 70 blood samples was collected from n=35 patients. cfHPV-DNA was successfully detected in 25/35 (71%) patients; of them, 8 patients had some surgical pretreatment when the sample was collected. A significant correlation between tumor burden and cfHPV-DNA detection was observed: while cfHPV-DNA was detectable in most patients (20/22) with locally advanced or metastatic disease (FIGO IB3 – IVB), detection was successful in only 5/13 patients with early-stage disease (FIGO IA – IB2), p<0.005. When pretreated patients were excluded, the detectable rate was 100% (18/18) for advanced stages and 55% (5/9) for early stages. HPV-types detected in plasma samples matched results from tumor tissue HPV testing. Sequential sampling for patients under primary chemoradiation showed a dynamic decrease of cfHPV-DNA levels corresponding treatment response in all patients.

Conclusion In this proof-of-concept study we were able to detect cfHPV-DNA in plasma samples of patients with primary and recurrent cervical cancer. Our findings may hold potential to develop a powerful and easily accessible tool in cervical cancer management.

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