Association of HLA-G alleles with type-specific HPV seropositivity and seropersistence in unvaccinated women: A prospective cohort study

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INTRODUCTION: The human leukocyte antigen G (HLA-G) allele repertoire is crucial for cell-mediated immune responses. While HLA-G's role in human papillomavirus (HPV) infection is increasingly studied, research on HLA-G and humoral immunity remains limited. This study aimed to establish whether HLA-G alleles impact type-specific HPV serological outcomes. METHODS: Altogether, 265 women from the prospective Finnish Family HPV cohort study were included. HLA-G alleles and genotypes were determined by direct DNA-sequencing. Blood samples were collected at baseline (36 weeks of pregnancy) and at 12, 24 and 36 months of follow-up. Antibodies to the L1 antigen of HPV types 6, 11, 16, 18 and 45 were determined using multiplex serology. RESULTS*: Six different HLA-G alleles and genotypes were identified. The most common allele was 01:01:01 (87.2%) followed by *01:01:02 (39.6%). Heterozygote carriage of HLA-G*01:01:01 increased the likelihood of HPV16 seropersistence (OR 2.99; 95%CI 1.13-7.91). Allele *01:01:03 was associated with both increased HPV11 seropositivity (OR 3.93; 95%CI 1.49-10.39) and seropersistence (OR 4.42; 95%CI 1.56-12.49). Conversely, allele *01:04:01 showed a protective association against HPV11 seropositivity (OR 0.43, 95%CI 0.20-0.91). CONCLUSIONS: HLA-G alleles and genotypes may influence seropositivity and seropersistence to L1 antigen of both low-risk HPV11 and high-risk HPV16 genotypes. Given study limitations, these findings should be considered exploratory, and further research is warranted to establish the detailed mechanisms by which HLA-G influences HPV-related humoral immunity and disease outcomes.

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