title: Association of human leukocyte antigen and T cell message with human papillomavirus 16-positive cervical neoplasia in Japanese women.
abstract: To investigate whether an association exists between human leukocyte antigen (HLA) haplotype and cervical neoplasia within the Japanese population, we analyzed the human papillomavirus (HPV) genotypes, the HLA class I specificities and class II alleles, and the T-cell responses in the lesions of patients with cervical neoplasia. Eighty-one patients, consisting of 62 cervical intraepithelial neoplasia (CIN) lesions and 19 invasive cervical cancers (ICC), were examined. The frequencies of HPV infection in the CIN I/II and CIN III/ICC groups were 68.0% (17/25) and 80.4% (45/56), respectively. All patients and 138 local Japanese controls were analyzed for HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1. For major histocompatibility complex (MHC) class II HLA-DRB1 alleles, the frequency of DRB1*0901 was significantly elevated in HPV 16-positive CIN III/ICC patients compared with controls (59.3% versus 29.7%, P = 0.0031, OR = 3.44). Similarly for the HLA-DQB1 alleles, a significant increase in the DQB1*03032 frequency was observed in HPV 16-positive CIN III/ICC patients compared with controls (59.3% versus 28.3%, P = 0.0018, OR = 3.69). In the analysis of the T-cell responses in the lesions, Fas ligand was detected at a decreased frequency in HPV 16-positive CIN III/ICC patients with the HLA-DRB1*0901-DQB1*03032 haplotype. The presence of helper T cell-specific messenger RNAs in the cervical lesions supports an association among MHC class II, helper T cells, the immune response to HPV, and the development of cervical carcinoma. Accordingly, a specific MHC class II haplotype, DRB1*0901-DQB1*03032, may be a risk factor for cervical carcinoma in the Japanese population.
authors: Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical School, Saitama, Japan. makimaki@saitama-med.ac.jp
authors: M
authors: M
authors: Saito
authors: M
authors: M
authors: Okubo
authors: R
authors: R
authors: Hirata
authors: S
authors: S
authors: Takeda
authors: H
authors: H
authors: Maeda
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002277:Carcinoma / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan; D054353:Perforin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
chemical_list: D053222:Fas Ligand Protein; D006680:HLA Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D054353:Perforin