Dataset Information

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study.

ABSTRACT: Mechanisms for the control and resolution of human papillomavirus (HPV) infection of the cervix include the local production of cytokines, which control recruitment and function of cells integral to pathogen control. We established a cohort of women for long-term follow-up to examine the mucosal expression of antiviral (IFN-?2), Type-1 (IFN-?, IL-12), regulatory (IL-10), and proinflammatory (IL-1?, IL-1?, IL-6, IL-8, MIP-1?, and TNF) cytokines in association with the clearance of incident cervical HPV infection. Interviews and specimens for HPV DNA analysis and cytokine protein measurement were obtained at baseline and at 4-month intervals. A Cox proportional hazards model was used to study the relationship between clearance of 107 high-risk and 111 low-risk incident HPV infections and cytokine levels among 154 women. Positive changes from baseline levels of IL-10, IL-12, MIP-1?, and TNF were associated with significantly longer times to type-specific HPV clearance. Inverse trends in the hazard ratios associated with clearance of high-risk HPV infections were monotonic and significant for IL-12 (ptrend ?=?0.02) and TNF (ptrend ?=?0.02); the likelihood of high-risk HPV clearance was reduced by 65% and 67%, respectively, among women in the highest as compared with the lowest quartile of change from baseline. Our results suggest that in women with a nontransient cervical HPV infection, proinflammatory, Type-1, and regulatory cytokines are elevated, underscoring the long-term commitment of local immune mediators to viral eradication.

SUBMITTER: Scott ME

PROVIDER: S-EPMC3732505 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study.

Scott Mark E ME Shvetsov Yurii B YB Thompson Pamela J PJ Hernandez Brenda Y BY Zhu Xuemei X Wilkens Lynne R LR Killeen Jeffrey J Vo Dien D DD Moscicki Anna-Barbara AB Goodman Marc T MT

International journal of cancer 20130316 5

Mechanisms for the control and resolution of human papillomavirus (HPV) infection of the cervix include the local production of cytokines, which control recruitment and function of cells integral to pathogen control. We established a cohort of women for long-term follow-up to examine the mucosal expression of antiviral (IFN-α2), Type-1 (IFN-γ, IL-12), regulatory (IL-10), and proinflammatory (IL-1α, IL-1β, IL-6, IL-8, MIP-1α, and TNF) cytokines in association with the clearance of incident cervic ...[more]

PMID: 23436563

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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: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?<?5 X 10-?8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p?=?1.43?×?10-?6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p?=?7.15?×?10-?8), NR5A2 (OR: 3.65, p?=?2.03?×?10-?7) and MIR365-2 (OR: 7.71, p?=?2.63?×?10-?7) gene regions. CONCLUSIONS:This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

Dataset Information

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study.

Publications

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study.

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