Original Article

Tumor Biology

, Volume 37, Issue 6, pp 8019-8025

First online:

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 JiaAffiliated withDepartment of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University 
  • , Jing HanAffiliated withDepartment of Epidemiology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province 
  • , Dong HangAffiliated withDepartment of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University
  • , Jie JiangAffiliated withDepartment of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University
  • , Minjie WangAffiliated withDepartment of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • , Baojun WeiAffiliated withDepartment of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • , Juncheng DaiAffiliated withDepartment of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University
  • , Kai ZhangAffiliated withDepartment of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • , Lanwei GuoAffiliated withProgram Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • , Jun QiAffiliated withDepartment of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • , Hongxia MaAffiliated withDepartment of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical University
    • , Jufang ShiAffiliated withProgram Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • , Jiansong RenAffiliated withProgram Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • , Zhibin HuAffiliated withDepartment of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical SciencesState Key Laboratory of Reproductive Medicine, Nanjing Medical University
    • , Min DaiAffiliated withProgram Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Email author 
    • , Ni LiAffiliated withProgram Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Email author 

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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 (P for 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

HLA Genetic variants HPV Interaction Cervical cancer