Defining the genetic susceptibility to cervical neoplasia—A genome-wide association study

Research output: Contribution to journalArticle


A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.


  • Paul J Leo
  • Margaret M. Madeleine
  • Sophia S Wang
  • Stephen M. Schwartz
  • Felicity S. Newell
  • Ulrika Pettersson-Kymmer
  • Goran Hallmans
  • Sven Tiews
  • Winfried Steinberg
  • Janet S. Rader
  • Felipe A Castro
  • Mahboobeh Safaeian
  • Eduardo L. Franco
  • François Coutlée
  • Claes Ohlsson
  • Adrian Cortes
  • Mhairi Marshall
  • Pamela Mukhopadhyay
  • Katie Cremin
  • Lisa G. Johnson
  • Suzanne M Garland
  • Sepehr N. Tabrizi
  • Nicolas Wentzensen
  • Freddy Sitas
  • Julian Little
  • Maggie Cruickshank
  • Ian H. Frazer
  • Allan Hildesheim
  • Matthew A Brown
External organisations
  • Queensland University of Technology
  • Fred Hutchinson Cancer Research Center
  • City of Hope National Medical Center
  • Umeå University
  • German Cancer Research Centre
  • Dr.Steinberg GmbH
  • Medical College of Wisconsin
  • National Cancer Institute, USA
  • McGill University
  • University of Montreal, Canada
  • Sahlgrenska Academy
  • The Royal Women’s Hospital
  • University of Melbourne
  • Cancer Council New South Wales
  • University of Sydney
  • University of New South Wales
  • University of Ottawa
  • University of Aberdeen
  • University of Queensland
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • GWAS, cervical neoplasia, genetic susceptibility
Original languageEnglish
Article numbere1006866
JournalPLoS Genetics
Issue number8
Publication statusPublished - 2017 Aug 1
Publication categoryResearch