Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Institut Curie
  • Antoni van Leeuwenhoek Hospital
  • Erasmus University Rotterdam
  • Oncology Institute of Vojvodina
  • Service d’oncologie médicale
  • Publica Institutul Oncologic
  • Institut Gustave Roussy
  • ARCAGY-GINECO
  • Institut Pasteur Paris
  • Quanticsoft
  • Victor Babes University of Medicine and Pharmacy
  • Hannover Medical School (MHH)
  • Centre Georges-François Leclerc
  • Centre régional de lutte du cancer Val d'Aurelle
  • INSERM - Institut national de la santé et de la recherche médicale

Abstract

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.

Details

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalBritish journal of cancer
Volume124
Issue number4
Publication statusPublished - 16 Feb 2021
Peer-reviewedYes

External IDs

PubMed 33191407

Keywords

Sustainable Development Goals

ASJC Scopus subject areas