HLA-B*15 showed a negative association with HPV-16-positive CaCx (0.1, 0.01), whereas DRB1*04 exhibited protection to both HPV-16-positive CaCx and persistent HPV-16 infection (0.3, 0.0001 and 0.1, 0.0002, respectively).
Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.
Variation in LD between the classic HLA loci, rs9272143 and rs67841474 between populations may explain the different associations of HLA-B*07 and DRB1*1501-DQB1*0602 with cervical cancer between studies.
Among the 25 specific alleles, six (DRB1*0301, *0403,*0404, *0803, *1312 and *1502) were associated with an increased risk cervical cancer in all studies.
Haplotype analysis highlighted the significant association of HLA- DRB1*07:01-DQB1*02:02 and HLA DRB1*10:01-DQB1*05:01 with cervical cancer, while HLA-DRB1*14:04-DQB1*05:03 and DRB1*15:01-DQB1*06:01 conferred decreased risk for cervical cancer.
We also confirmed previously reported associations of B*0702 and DRB1*1501-DQB1*0602 with susceptibility to and DRB1*1301-DQA1*0103-DQB1*0603 with protection against cervical cancer.
The DRB1*13 allele/DRB1*13-DQB1*06 haplotype was strongly protective against risk to HPV infection (p(c) < 0.002) as well as cervical cancer (p(c) 0.01).
Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women.
In a similar fashion, the occurrence of DRB1 *13-DQB1 *06 (OR, 0.17; 95% CI, 0.04-0.80) haplotype was significantly lower in the study patients compared with the controls and may confer a decreased risk of CC among Han race population in the Guangdong Province of China.
These results indicate that HLA-DPB1*1301 may confer susceptibility to cervical cancer, and the haplotypes DRB1*150101-DQB1*0602 and DRB1*070101-DQB1*0201 may contribute to the resistance to the development of cervical cancer among Chinese women.
Observations from this study confirm earlier findings of a negative association between DRB1*13 and cervical cancer and suggest that specific DRB1-DQB1 haplotype combinations, rather than individual DQB1*03 alleles, increase the risk for cervical cancer.
In previous studies, the HLA class II haplotype HLA DRB1*0401-DQB1*0301 was shown to correlate with susceptibility to HPV infection, CIN and cervical cancer while DRB1*0101-DQB1*0501 indicated protection.
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.