Tumor Biology

, Volume 37, Issue 6, pp 8019–8025

HLA-DP is the cervical cancer susceptibility loci among women infected by high-risk human papillomavirus: potential implication for triage of human papillomavirus-positive women

  • Meiqun Jia
  • Jing Han
  • Dong Hang
  • Jie Jiang
  • Minjie Wang
  • Baojun Wei
  • Juncheng Dai
  • Kai Zhang
  • Lanwei Guo
  • Jun Qi
  • Hongxia Ma
  • Jufang Shi
  • Jiansong Ren
  • Zhibin Hu
  • Min Dai
  • Ni Li
Original Article

DOI: 10.1007/s13277-015-4673-7

Cite this article as:
Jia, M., Han, J., Hang, D. et al. Tumor Biol. (2016) 37: 8019. doi:10.1007/s13277-015-4673-7

Abstract

Given that only a small proportion of women infected by high-risk human papillomavirus (hrHPV) develop cervical cancer, it’s important to identify biomarkers for distinguishing women with hrHPV positivity who might develop cervical cancer from the transient infections. In this study, we hypothesized that human leukocyte antigens (HLA) susceptibility alleles might contribute to cervical cancer risk among females infected by hrHPV, and interact with hrHPV types. A case-control study with 593 cervical cancer cases and 407 controls (all hrHPV positive) was conducted to evaluate the effect of eight HLA-related single-nucleotide polymorphisms (SNPs) and their interactions with hrHPV types on the risk of cervical cancer. Three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) were found to be significantly associated with risk of cervical cancer (rs4282438: odds ratio (OR) = 0.72, 95 % confidence interval (CI) = 0.56–0.93; rs3117027: OR = 1.41, 95 % CI = 1.10–1.83; and rs3077: OR = 1.37, 95 % CI = 1.04–1.80) among women infected with hrHPV. An additive interaction between HPV16 and rs4282438 for cervical cancer risk was also found (Pfor interaction = 0.002). Compared with subjects carrying variant genotypes (GG/TG) and non-HPV16 infections, those carrying wild-type genotype (TT) of rs4282438 and HPV16 positive had a 5.22-fold increased risk of cervical cancer (95 % CI = 3.39–8.04). Our study supported that certain HLA-DP alleles in concert with HPV16 could have a predisposition for cervical cancer development, which may be translated for triage of hrHPV-positive women.

Keywords

HLAGenetic variantsHPVInteractionCervical cancer

Abbreviations

hrHPV

High-risk human papillomavirus

SNPs

Single-nucleotide polymorphisms

HLA

Human leukocyte antigens

GWAS

Genome-wide association studies

LBC

Liquid-based cytologically

ASCUS

Atypical squamous cells of undetermined significance

Ors

Odds ratios

CIs

Confidence intervals

HWE

Hardy-Weinberg equilibrium

MHC

Major histocompatibility complex

Supplementary material

13277_2015_4673_MOESM1_ESM.doc (1.5 mb)
ESM 1(DOC 1524 kb)

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Meiqun Jia
    • 1
  • Jing Han
    • 2
  • Dong Hang
    • 1
  • Jie Jiang
    • 1
  • Minjie Wang
    • 3
  • Baojun Wei
    • 3
  • Juncheng Dai
    • 1
  • Kai Zhang
    • 4
  • Lanwei Guo
    • 5
  • Jun Qi
    • 4
  • Hongxia Ma
    • 1
    • 6
  • Jufang Shi
    • 5
  • Jiansong Ren
    • 5
  • Zhibin Hu
    • 3
    • 6
  • Min Dai
    • 5
  • Ni Li
    • 5
  1. 1.Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public HealthNanjing Medical UniversityNanjingChina
  2. 2.Department of EpidemiologyNanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu ProvinceNanjingPeople’s Republic of China
  3. 3.Department of Clinical LaboratoryCancer Institute and Hospital, Chinese Academy of Medical SciencesBeijingChina
  4. 4.Department of Cancer Prevention, Cancer Institute and HospitalChinese Academy of Medical SciencesBeijingChina
  5. 5.Program Office for Cancer Screening in Urban China, Cancer Institute and HospitalChinese Academy of Medical SciencesBeijingChina
  6. 6.State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjingChina