BackgroundThe 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. MethodsCervical 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. ResultsHLA-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. ConclusionsThese 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.