HLA class II alleles associated with infection by HPV16 in cervical cancer in situ.

HLA class II alleles have been associated with an increased risk of developing cervical cancer through infection with oncogenic forms of human papilloma virus (HPV). We have examined the association of variation at the DRB1 and DQB1 loci with HPV16 infection and risk of development of cervical cancer by analysis of 440 cases diagnosed with cervical cancer in situ and 476 age-matched controls in a retrospective case-control study. The infection history of a woman was studied by analysis of cervical smears taken at multiple times during a period of up to 27 years (1969-95). The frequency of a number of alleles are either increased (DRB10801, DRB11501, DQB10402 and DQB10602) or decreased (DRB10101, DRB11301, DQB10501 and DQB10603) in the cancer patients compared to the controls. After correction for multiple testing, only the DQB10602 and the DRB11501 alleles remain associated with cancer and only in HPV16-infected patients (DQB10602: 102/264 (39%) vs. 130/476 (28%), p = 0.028 and DRB11501: 104/259 (40%) vs. 132/469 (28%), p = 0.027). These alleles are associated primarily with infection by HPV and only indirectly affect the risk of developing cervical cancer in situ. To study the impact of these alleles on persistence of infection, women with short-term infections were compared to those with long-term infections. Carriers of DQB10602 and DRB11501 were more frequent in the group with long-term HPV infections, indicating that these class II alleles contribute to the inability to clear an HPV infection.