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.