Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in northern Sweden

HLA genes have been shown to be associated with cervical intraepithelial ne oplasia (CIN), a precursor of cervical cancer, The human papillomaviruses ( HPV) types 16 and 18 are the major environmental cause of this disease. Bec ause the immune system plays an important role in the control of HPV infect ion, the association of polymorphic HLA could lead to a different immune re sponse to control the development of cervical cancer. The aim of this study was to analyze the association between CW and a microsatellite polymorphis m of tumor necrosis factor (TNFa) taking HPV exposure and CIN-associated HL A haplotypes into account. In a nested case-control study in northern Swede n, 64 patients and 147 controls matched for age and sex and derived from th e same population-based cohort were typed for TNFA, HLA-DR, and DQ and assa yed for antibodies to HPV types 16 and 18, TNFa polymorphism was not associ ated with CIN per se. However, there was a significant increase in the freq uency of TNFa-11 among HPV16-positive and HLA DR15-DQ6 (B*0602) patients co mpared with HPV16- and MA-DQ6-negative patients (odds ratios, 5.4 and 9.3, respectively). The relative risk for CIN conferred by the combination of TN Fa-11, HLA-DQ6 and HPV 16 positivity was 15, Our study suggests that the TN Fa-11 allele is associated with HPV16 infection and associated with CIN in combination with HLA-DQB but not by itself.