A meta-analysis of association of Human Leukocyte Antigens A, B, C, DR and DQ with Human Papillomavirus 16 infection

Human Papillomavirus (HPV) induced cervical cancer (CaCx) is a major health problem in women from both developing and developed regions of the world. This virus accounts for > 95% of the CaCx cases with a preponderance of HPV type -16 (65%). Paradoxically HPV-16 is prevalent even in the cervix of healthier women and anti HPV-16 T-cell response is considered critical for the viral clearance. Studies on HLA association with HPV-16 infection and cervical cancer have yielded varied HLA associations in different epidemiological settings. To validate these associations, we performed a meta-analysis of HLA-A, B, C, DR and DQ association with HPV-16 infection. Of the 1409 studies retrieved, 26 qualified for meta-analysis based on stringent inclusion and exclusion criteria. HLA-B*47, B*57, DRB1*10, DRB1*15 and DQB1*0303 were significantly associated with HPV-16 infection (OR = 3.4, 1.8, 1.5, 1.1 and 1.5 respectively). HLA-B*49, B*39, A28 (serotype), C*04 and DRB1*13 were negatively associated with HPV-16 (OR = 0.5, 0.6, 0.7, 0.7, and 0.7 respectively). Certain HLA alleles such as B*07, DRB1*15, DRB1*11 and DRB1*07 showed weakly positive associations. A comprehensive analysis coupling HPV-16 antigenic diversity and the HLA variation in various global populations shall provide further insights into the immunogenetic predisposition to HPV-16 and shall help identify host-parasite co-evolution.