To comprehensively explore the relationship between human leukocyte antigen (HLA) class I alleles and cervical neoplasia, a subset of participants from 3 large US and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects were women with cervical cancer or high-grade squamous epithelial lesions (HSILs; n = 365) or low-grade squamous epithelial lesions (LSILs; n = 275) or who were cytologically normal (control subjects; n = 681). Allele-disease associations were assessed by logistic regression analysis. Consistent associations across all studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95% confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37-1.04) for LSILs, compared with control subjects and adjusted for study. This finding supports the hypothesis that a single allele may be sufficient to confer protection against cervical neoplasia. Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia.
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