HLA DQA1 and DQB1 Loci in Honduran Women with Cervical Dysplasia and Invasive Cervical Carcinoma and Their Relationship to Human Papillomavirus Infection
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 HPY peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women
