Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk

Cancer. 2012 Jan 1;118(1):223-31. doi: 10.1002/cncr.26227. Epub 2011 Jun 20.

Abstract

Background: Only a small proportion of women infected with human papillomavirus type 18 (HPV18) may progress to persistent infection and cervical neoplasia. This community-based cohort study aimed to assess associations with human leukocyte antigen (HLA) class II genotypes for natural infection of HPV18 and subsequent risk of cervical neoplasia.

Methods: Among 10,190 cytologically normal participants, 125 with HPV18 infection were identified by HPV blot kit. HPV18 viral load at study entry was examined by real-time polymerase chain reaction; persistent infection was defined as HPV18 infection at 2 consecutive examinations.

Results: There was a significant association between HLA-DRB1*0403 allele and high HPV18 viral load (>1000 copies in 50 ng of total DNA) at study entry (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection (OR, 13.3; 95% CI, 1.7-105.9). HLA-DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5).

Conclusions: HLA-DRB1*0403 allele and HLA-DRB1*0405-DQA1*0301-DQB1*0302 haplotype may play important roles in determination of high viral load and persistent infection of HPV18 and subsequent cervical neoplasia risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Female
  • Genotype
  • HLA Antigens / genetics
  • Histocompatibility Antigens Class II / genetics*
  • Human papillomavirus 18*
  • Humans
  • Middle Aged
  • Papillomavirus Infections / genetics*
  • Risk Factors
  • Uterine Cervical Dysplasia / genetics*
  • Viral Load

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class II