HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection

Hum Biol. 1999 Jun;71(3):367-79.

Abstract

Molecular and epidemiological studies have demonstrated that certain types of human papillomavirus (HPV), mainly HPV-16 and HPV-18, are the primary causes of cervical cancer and its precursor lesions; there is now evidence for a clear association with specific HLA class I and class II loci contributing independently to the expression of cervical cancer. Among Honduran women carcinoma of the cervix is the most common type of cancer, and infections with high-risk HPV types are highly prevalent. To study the interactive role of viral-host genetics, we performed PCR amplification of DNA and sequence-specific oligonucleotide probe typing on cervical scrapes from 49 women [24 with cervical intraepithelial neoplasia stage III or cervical cancer (severe cases) and 25 with stage I or II cervical intraepithelial neoplasia (mild cases)] and 75 control subjects to look for possible associations between HPV and HLA class II DQA1 and DQB1 alleles in the development of dysplasias and invasive cancer. This analysis revealed a predominance of HLA-DQA1*0301 among severe-case patients [relative risk (RR) = 3.45, p = 0.008), whereas DQA1*0501 was negatively associated (RR = 0.30, p = 0.03), suggesting a protective effect of this allele. HPV typing showed a decreased relative risk among the HPV-16 or HPV-18 carrying patients and other HPV-related positive patients in the presence of DQB1*0602 compared with positive control subjects (p = 0.04). No statistically significant allele frequency difference was observed between mild dysplasia cases and control subjects. The results suggest that DQA1*03011, which is in linkage desequilibrium with all HLA-DR4 alleles, confers an increased risk for severe cervical dysplasia and invasive cancer, whereas DQA1*0501, which is in several DR52 haplotypes, has a protective effect. Furthermore, specific HLA-DQB1 sequences may be important in determining the immune response to HPV peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Disease Progression
  • Female
  • Gene Expression
  • Genes, MHC Class I
  • Genes, MHC Class II
  • Genetic Predisposition to Disease
  • Honduras / epidemiology
  • Humans
  • Middle Aged
  • Papillomaviridae / classification
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / genetics*
  • Polymerase Chain Reaction
  • Prevalence
  • Reference Values
  • Risk Assessment
  • Sampling Studies
  • Tumor Virus Infections / epidemiology
  • Tumor Virus Infections / genetics*
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / genetics*