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

HLA class II alleles have been associated with an increased risk of develop ing cervical cancer through infection with oncogenic forms of human papillo ma virus (HPV). We have examined the association of variation at the DRBI a nd DQBI loci with HPV16 infection and risk of development of cervical cance r by analysis of 440 cases diagnosed with cervical cancer in situ and 476 a ge-matched controls in a retrospective case-control study. The infection hi story of a woman was studied by analysis of cervical smears taken at multip le times during a period of up to 27 years (1969-95). The frequency of a nu mber of alleles are either increased (DRB1*0801, DRB1*1501, DQB1*0402 and D QB1*0602) or decreased (DRB1*0101, DRB1*1301, DQB1*0501 and DQB1*0603) in t he cancer patients compared to the controls. After correction for multiple testing, only the DQB1*0602 and the DRB1*1501 alleles remain associated wit h cancer and only in HPV16-infected patients (DQB1*0602: 102/264 (39%) vs. 130/ 476 (28%), p = 0.028 and DRB1*1501: 104/259 (40%) vs. 132/ 469 (28%), p = 0.027). These alleles are associated primarily with infection by HPV an d only indirectly affect the risk of developing cervical cancer in situ. To study the impact of these alleles on persistence of infection, women with shortterm infections were compared to those with long-term infections. Carr iers of DQB1*0602 and DRB1*1501 were more frequent in the group with long-t erm HPV infections, indicating that these class II alleles contribute to th e inability to clear an HPV infection. (C) 2001 Wilely-Liss, Inc.