title: Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Chuang
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Hu
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Chen
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lin
authors.forename: Borheng
authors.initials: B
authors.lastname: Lee
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Mei-Hung
authors.initials: MH
authors.lastname: Pan
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D052161:Human papillomavirus 18; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics*; D012307:Risk Factors; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II