Geographic distribution of cervical cancer-associated human leucocyte antigens and cervical cancer incidence in Finland

Abstract

Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1-2.0); B7 (1.5, 1.1-2.0); B15 (0.6, 0.4-0.8); DR2 (1.2, 1.1-1.4) and DR6 (0.6, 0.5-0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation.