HUMAN-LEUKOCYTE ANTIGEN CLASS I II ALLELES AND DEVELOPMENT OF HUMAN PAPILLOMAVIRUS-RELATED CERVICAL NEOPLASIA - RESULTS FROM A CASE-CONTROLSTUDY CONDUCTED IN THE UNITED-STATES/

The host immune response to human papillomaviruses (HPVs) is believed to be an important determinant of progression of HPV-associated cervic al neoplasia, Human leukocyte antigens (HLAs) are important in the pre sentation of foreign antigens to the immune system. Previous studies h ave suggested a possible association between HLA and cervical neoplasi a, but the specific alleles found to be associated with disease have v aried between studies. To further evaluate this issue, we conducted a nested case-control study within a 24,000-woman cohort study in the Un ited States. A total of 711 women were selected for the study: 141 wom en diagnosed with high-grade squamous intraepithelial lesions (HSILs) of the cervix; 202 women diagnosed with low-grade SILs (LSILs); 166 wo men with no history of cervical neoplasia, but evidence of HPV-16 infe ction; and 202 women with no history of cervical abnormalities and who were HPV negative during follow-up as part of our cohort, Cervicovagi nal lavage samples collected from participants were used for HPV testi ng by L1 consensus primer PCR and the Hybrid Capture tube test methods . DNA extracted from these same lavage samples were used for PCR-based HLA genotyping, Our results suggest a positive association between HL A B7 and KLA DQB10302 and disease. A negative association with diseas e was observed for HLA DRB11501-DQB1*0602 and DRB1*13, Associations w ere strongest when analyses were restricted to HPV-16-positive cases a s follows. Compared with women who were cytologically normal and HPV n egative, HLA B7 was associated with a 1.5-fold increased risk of HPV/L SIL [95% confidence interval (CI) = 0.95-2.5] and a 2.5-fold increased risk of HSIL (95% CI = 1.2-5.1). HLA DQB10302 was associated with a 1.5-fold increased risk of HPV/LSIL (95% CI = 0.94-2.4) and a 1.7-fold increased risk of HSIL (95% CI = 0.84-3.5), HLA DRB11501-DQB1*0602 w as associated with a decreased risk of HSIL [relative risk (RR) = 0.21 ; 95% CI = 0.07-0.62], HLA DRB113 was associated with a decreased ris k of HPV/LSIL (RR = 0.78; 95% CI = 0.51-1.2) and HSIL (RR = 0.63; 95% CI = 0.30-1.3), individuals who were either homozygous for DQB10302 o r carriers of both B7 and DQB10302 were found to be at highest risk o f disease (RR = 4.5, 95% CI = 1.5-14 for HPV/LSIL; and RR = 9.0, 95% C I = 2.4-34 for HSIL), No synergistic effect was observed for the allel es found to be associated with reduced risk of cervical neoplasia. Our findings support previous studies that have found HLA B7 and DQB1030 2 to be positively associated with cervical neoplasia and are consiste nt with those that have suggested that DRB113 is negatively associate d with disease, but do not confirm previous assertions that DRB11501- DQB10602 increases the risk of cervical disease.