Persistent high-risk human papillomavirus (HPV) infection has been associated with increased risk for cervical precancerous lesions and cancer. The host’s genetic variability is known to play a role in the development of cervical cancer. The human leukocyte antigen (HLA) genes are highly polymorphic and have shown to be important risk determinants of HPV infection persistence and disease progression. HLA class I and II cell surface molecules regulate the host’s immune system by presenting HPV-derived peptides to T-cells. The activation of T-cell response may vary depending on the HLA allele polymorphism. The engagement of the T-cell receptor with the HPV peptide-HLA complex to create an active costimulatory signal is essential for the activation of the T-cell response. Functional peptide presentation by both HLA class I and II molecules is needed to activate efficient helper and effector T-cell responses in HPV infection recognition and clearance. Some of these HLA risk alleles could also be used as preventive tools in the detection of HPV-induced cervical lesions and cancer. These HLA alleles, together with HPV vaccines, could potentially offer possible solutions for reducing HPV-induced cervical cancer as well as other HPV-related cancers.

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20–0.24, 95% CI range of 0.06–0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11–0.84) and persistent (OR 0.24, 95% CI 0.08–0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34–18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23–51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57–117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies.

Purpose: Human leukocyte antigen (HLA)-G may have an important role in the natural history of human papillomavirus (HPV) infection. Our aim was to evaluate the role of HLA-G in the outcome of genital and oral HPV infections in women. Methods: Analyses included 306 women from the Finnish Family HPV-study and were followed-up for six years. Genital and oral samples were tested for 24 different HPV types with multiplex HPV genotyping. HLA-G alleles were determined through direct DNA-sequencing. Unconditional logistic regression was used to determine the associations between HLA-G genotypes and HPV infection outcomes.Results: Nine HLA-G alleles were identified. Most common HLA-G genotypes were the wild type G*01:01:01/01:01:01 (31.3%) followed by G*01:01:01/01:01:02 (26.8%). G*01:01:01/01:01:01 genotype was associated with increased risk of oral HPV infections by any HPV type or single-type with OR=1.86 (95% CI 1.14-3.04) and 2.22 (95% CI 1.14 - 3.71), respectively. G*04:01+ allele and the G*01:01:01/01:04:01 genotype both protected from any and single oral HPV infections; OR=0.46 (95% CI 0.23-0.89) and 0.53 (95% CI 0.23-0.97), respectively. G*01:01:02/01:04:01 genotype increased significantly the risk of infertility and its treatments, with respective OR= 5.06 (95% CI 1.22-21.02) and OR=9.07 (95% CI 1.22-39.50). Both HLA-G alleles and genotypes showed several significant associations with the outcomes of oral HPV infections, but none of them had any impact on the outcomes of genital HPV infections in these women. Conclusion: The host HLA-G genotypes appear to impact the outcomes of oral HPV infections in women but have little if any effect on genital HPV status or infection outcomes.

Backround Human leukocyte antigen (HLA)-G may have an important role in the natural history of human papillomavirus (HPV) infection. Our aim was to evaluate the role of HLA-G in the outcome of genital and oral HPV infections in women. Methods Analyses included 306 women from the Finnish Family HPV-study and were followed-up for six years. Genital and oral samples were tested for 24 different HPV types with multiplex HPV genotyping. HLA-G alleles were determined through direct DNA-sequencing. Unconditional logistic regression was used to determine the associations between HLA-G genotypes and HPV infection outcomes. Results Ten HLA-G alleles were identified. Most common HLA-G genotypes were the wild type G*01:01:01/01:01:01 (31.3%) followed by G*01:01:01/01:01:02 (26.8%). G*01:01:01/01:01:01 genotype was associated with increased risk of oral HPV infections by any HPV type or single-type with OR = 1.86 (95% CI 1.14–3.04, P = 0.01) and 2.22 (95% CI 1.14–3.71, P = 0.02), respectively. G*04:01+ allele and the G*01:01:01/01:04:01 genotype both protected from any and single oral HPV infections; OR = 0.46 (95% CI 0.23–0.89, P = 0.02) and 0.53 (95% CI 0.23–0.97, P = 0.03), respectively. G*01:01:02/01:04:01 genotype increased significantly the risk of infertility and its treatments, with respective OR = 5.06 (95% CI 1.22–21.02, P = 0.03) and OR = 9.07 (95% CI 1.22–39.50, P = 0.03). Both HLA-G alleles and genotypes showed several significant associations with the outcomes of oral HPV infections, but none of them had any impact on the outcomes of genital HPV infections in these women. Conclusions The host HLA-G genotypes appear to impact the outcomes of oral HPV infections in women but have little if any effect on genital HPV status or infection outcomes.