title: HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection.
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.
authors.affiliation: Department of Immunogenetics, INDRE, SSA, Mexico City.
authors.forename: A
authors.initials: A
authors.lastname: Ferrera
authors.forename: A
authors.initials: A
authors.lastname: Olivo
authors.forename: C
authors.initials: C
authors.lastname: Alaez
authors.forename: W J
authors.initials: WJ
authors.lastname: Melchers
authors.forename: C
authors.initials: C
authors.lastname: Gorodezky
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006721:Honduras / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics*