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Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

ABSTRACT: BACKGROUND:Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. METHODS:Participants were 517 Nigerian women evaluated at baseline and 6?months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. RESULTS:The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p?

SUBMITTER: Adebamowo SN

PROVIDER: S-EPMC7682060 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

Adebamowo Sally N SN Adeyemo Adebowale A AA Rotimi Charles N CN Olaniyan Olayinka O Offiong Richard R Adebamowo Clement A CA

BMC medical genetics 20201123 1

<h4>Background</h4>Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.<h4>Methods</h4>Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF<sub>10</sub>/LiPA<sub>25</sub>. hrHPV infection was positive if at least one ...[more]

PMID: 33225922

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Project description:BackgroundPersistent cervical high-risk human papillomavirus (hrHPV) infection is a necessary cause of cervical cancer. However, the host genetic factors underlying its risk are not well understood. We hypothesized that immunogenetic variation plays a role in hrHPV infection and persistence. Therefore, we conducted a study of classical HLA alleles and their association with hrHPV infection and persistence among women.MethodsWe characterized HPV infection using SPF10/LiPA25in Nigerian women at baseline and at 6 months follow-up visits in 2014. hrHPV infection was prevalent if at least one carcinogenic HPV genotype was detected at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected at the baseline and follow-up visits. Classical HLA alleles were imputed from genotypes in the MHC region using the HLA genotype imputation with attribute bagging (HIBAG) algorithm. HLA association tests were conducted under additive genetic models.ResultsThe mean (±SD) age of the 517 study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive at baseline and 10% had persistent hrHPV infections. In multivariate regression models adjusted for age, HIV status and the first principal component, DQA1*01:02 and DQA1*02:01 were positively associated with prevalent but not persistent hrHPV infections, while DQA1*05:01 was negatively associated with prevalent hrHPV but positively associated with persistent cervical hrHPV infections. Four haplotypes (A*30:01-DQA1*05:01, B*07:02-C*07:02, B*07:02-DQA1*05:01 and C*07:02-DQA1*05:01) were significantly associated with prevalent cervical hrHPV infections and several haplotypes that included the DQA1*05:01 allelic variant were significantly associated with persistent cervical hrHPV infections. Six amino acid positions on DQα1 were associated with prevalent but not persistent cervical hrHPV infections.ConclusionsIn this first study to investigate the association between HLA alleles and persistent hrHPV in African women, we identified important risk alleles that merit further investigation. Our findings provide new insights into risk factors for hrHPV infection in African ancestry women.

Project description:Few studies have been conducted on the relationship between metabolic syndrome (MetS) and cervical human papillomavirus (HPV) incidence and persistent infection. We performed a prospective cohort study including 8598 female employees in Hunan, China. First, the subjects were stratified into HPV-negative (N = 7282) and HPV-positive (N = 1316) subgroups, according to the results of an HPV DNA test at baseline. Second, comparisons of the risks of HPV incident and persistent infection between MetS-positive (exposed) and MetS-negative (unexposed) groups were conducted among the HPV-negative and -positive subgroups, respectively. There were 976 (11.39%) subjects diagnosed with MetS and 1316 subjects diagnosed with HPV infection at baseline. The 12-month cumulative incidence of any type of HPV and high-risk type HPV were 7.28% (530/7282) and 6.26% (456/7282), respectively. Obesity was a modifier of the association between MetS and HPV incident infection. As long as obesity presented, MetS and hypertriglyceridemia were significantly associated with an increased risk of HPV incident infection (any-type or high-risk type) (adjusted risk ratios (RR) were 2.88 (95% confidence interval (CI): 1.16, 7.19) and 3.29 (95% CI: 1.47, 7.38), respectively). Among those infected with HPV at baseline, the 12-month type-specific persistence rates were 51.67% and 53.38% for any-type and high-risk type HPV, respectively. No interaction was found between obesity and MetS with regard to the risk of HPV persistence. After adjustment for confounding factors, MetS was still associated with increased risk of any-type HPV persistence (RRadj = 1.21, 95% CI: 1.05, 1.41) and high-risk type HPV persistence (RRadj = 1.25, 95% CI: 1.09, 1.46). No single metabolic component was associated with the risk of HPV persistence. The prevalence of MetS was 11.39% among the Hunan female occupational population. MetS was associated with an increased risk of persistent cervical HPV infection and also with an increased risk of HPV incident infection when obesity presented as well.

Project description:BackgroundHuman papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood.ObjectivesTo determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions.Study designWe included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated.ResultsMedian follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were -5.4% (95% confidence interval -19,10) and 0.3% (95% confidence interval -69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval -131, 82) and -211% (95% confidence interval -2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval -43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively.ConclusionWe find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies.

Dataset Information

Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

Publications

Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

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