HLA and KIR Associations of Cervical Neoplasia

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Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent. Results: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.


  • Xiao Bao
  • Aimee L. Hanson
  • Margaret M. Madeleine
  • Sophia S. Wang
  • Stephen M. Schwartz
  • Felicity Newell
  • Ulrika Pettersson-Kymmer
  • Sven Tiews
  • Winfried Steinberg
  • Janet S. Rader
  • Felipe 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
  • Cornelia Trimble
  • Julian Little
  • Maggie Cruickshank
  • Ian H. Frazer
  • Allan Hildesheim
  • Matthew A. Brown
  • Emma L. Duncan
  • Ying Pu Sun
  • Paul J. Leo
External organisations
  • First Affiliated Hospital of Zhengzhou University
  • Queensland University of Technology
  • University of Queensland
  • Princess Alexandra Hospital
  • Fred Hutchinson Cancer Research Center
  • City of Hope National Medical Center
  • Umeå University
  • German Cancer Research Centre
  • MVZ Labor für Cytopathologie Dr. Steinberg GmbH
  • Medical College of Wisconsin
  • McGill University
  • Centre hospitalier de l'Université de Montréal
  • University of Gothenburg
  • Murdoch Children's Research Institute
  • University of Melbourne
  • University of Sydney
  • University of New South Wales
  • Johns Hopkins University
  • University of Ottawa
  • University of Aberdeen
  • National Cancer Institute, NCI
  • Cancer Council New South Wales
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Infectious Medicine
Original languageEnglish
Pages (from-to)2006-2015
Number of pages10
JournalThe Journal of infectious diseases
Issue number12
Publication statusPublished - 2018 Dec 15
Publication categoryResearch