The association between human leukocyte antigen (HLA)-G polymorphisms and human papillomavirus (HPV) infection in Inuit women of northern Quebec

Abstract

Background: The human leukocyte antigen (HLA)-G molecules act as negative regulators of the immune response. We analyzed the associations between HLA G polymorphisms and human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) in Inuit women from Nunavik, northern Quebec.

Methods: Cervical specimens from a cohort study of 548 Inuit women were tested for HPV DNA. HPV genotypes were classified according to tissue-tropism groupings of alpha-papillomavirus species: alpha group 1 includes low risk (LR) cervical species, group 2 includes high risk (HR) cervical species, and group 3 includes LR vaginal species. HLA-G alleles were typed using direct DNA sequencing.

Results: HLA-G(∗)01:01:01 was associated with an increased risk of period prevalent alpha groups 1 (OR = 2.23, 95% CI:1.08-4.59) and 3 (OR = 1.70, 95% CI:1.09-2.65). The homozygous HLA-G(∗)01:04:01 genotype was associated with a decreased risk of alpha group 3 infection period prevalence (OR = 1.69 95% CI = 1.07-2.67). No HLA-G alleles were significantly associated with HPV persistence. HLA-G(∗)01:01:02, G(∗)01:04:01 and G(∗)01:06 were associated with high grade (HG)SIL, but the association did not reach statistical significance.

Conclusions: These results suggest that HLA-G polymorphisms play a role in the natural history of HPV infection, likely at the stage of host immune recognition. HLA-G polymorphisms interacted differently with the three alpha papillomavirus groups.