title: Association between human papillomavirus 16 E6 variants and human leukocyte antigen class I polymorphism in cervical cancer of Swedish women.
abstract: Persistent infection with human papillomavirus (HPV), particularly HPV16, represents the prime risk factor in cervical carcinogenesis. HPV variants (e.g., within the E6 gene) together with immunogenetic factors of the host may be responsible either for effective viral clearance, or alternatively, for viral persistence. Peripheral blood from 27 HPV16 positive Swedish women with cervical carcinoma, who had previously been tested for HPV16 E6 variants, was used for human leukocyte antigen (HLA) class I typing. Women with HLA-B*44, HLA-B*51, or HLA-B*57 who were infected with the HPV16 E6 variant L83V had an approximately four- to fivefold increased risk for cancer compared with controls (odds ratio [OR] = 3.5, 95% CI = 1.1-11.1, OR = 4.2, 95% CI = 1.19-14.69, or OR = 4.67, 95% CI = 1.2-18.6, respectively). Epitope predictive algorithm with SYFPEITHI revealed that the variant at amino acid 83 affects the binding affinity in association with HLA-B*44. Interestingly, the HLA-B*15 allele seems protective because it was absent in HPV16 positive cancer. It is concluded that specific HLA class I alleles, combined with certain HPV16 E6 variants, may be crucial for immune surveillance in cervical carcinogenesis. The evaluation of associations of HLA alleles with HPV variants may be helpful in defining prognostic markers and in designing vaccines capable of mediating immune protection against HPV infection.
authors.affiliation: Department of Medical Microbiology (I.Z.), University of Mainz, Mainz, Germany. zehbe@mail.uni-mainz.de
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Zehbe
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wikström
authors.forename: Rudi
authors.initials: R
authors.lastname: Henriksen
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
mesh_terms: D000465:Algorithms; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology; D030361:Papillomavirus Infections / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins; D012307:Risk Factors; D013548:Sweden; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D006680:HLA Antigens; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins