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Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort.

ABSTRACT: Cofactors might affect the risk of the rare progression from infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy to invasive cancer. Some studies have observed that Chlamydia trachomatis infection is associated with increased risk for cervical cancer. In a large prospective cohort, we assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV.We identified 182 women with prevalent and 132 women with incident histological cervical intraepithelial neoplasia grade 2 (CIN2), grade 3 (CIN3), or cervical cancer (CIN2+) in the Costa Rica HPV Natural History Study. Control subjects were 995 (approximately 10% of the 10?049) subjects who were randomly selected from the same study. Cervical HPV status at enrollment was determined by MY09/MY11 polymerase chain reaction amplification and dot-blot hybridization. The presence of C trachomatis DNA in cervical exfoliated cells at enrollment was determined by a novel serovar-specific polymerase chain reaction-based C trachomatis detection and genotyping assay. Plasma drawn at enrollment from each subject was used to determine C trachomatis immunoglobulin G (IgG) status. Logistic regression was used to examine the association between C trachomatis and CIN2+, taking into account possible confounding by HPV.C trachomatis positivity at enrollment was associated with CIN2+ and concurrent and subsequent carcinogenic HPV infection. To account for confounding by HPV status, we restricted the analysis to women positive for carcinogenic HPV DNA at enrollment and found no association between C trachomatis status (as assessed by DNA or IgG) at enrollment and combined prevalent and/or incident CIN2+ (for C trachomatis DNA positivity, odds ratio = 0.77, 95% confidence interval = 0.42 to 1.41; for C trachomatis seropositivity, odds ratio = 1.09, 95% confidence interval = 0.85 to 1.41).We found no association between C trachomatis status, as assessed by DNA or IgG, and risk of cervical premalignancy, after controlling for carcinogenic HPV-positive status. Previous positive associations between C trachomatis and cervical premalignancy could have been caused, in part, by an increased susceptibility to HPV infection.

SUBMITTER: Safaeian M

PROVIDER: S-EPMC2994864 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort.

Safaeian Mahboobeh M Quint Koen K Schiffman Mark M Rodriguez Ana Cecilia AC Wacholder Sholom S Herrero Rolando R Hildesheim Allan A Viscidi Raphael P RP Quint Wim W Burk Robert D RD

Journal of the National Cancer Institute 20101123 23

<h4>Background</h4>Cofactors might affect the risk of the rare progression from infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy to invasive cancer. Some studies have observed that Chlamydia trachomatis infection is associated with increased risk for cervical cancer. In a large prospective cohort, we assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV.<h4>Methods</h4>We identified 182 women with prevalent and 132 women wit ...[more]

PMID: 21098758

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Project description:BackgroundChlamydia is the most commonly diagnosed sexually transmitted infection worldwide. Mathematical models used to plan and assess control measures rely on accurate estimates of chlamydia's natural history, including the probability of transmission within a partnership. Several methods for estimating transmission probability have been proposed, but all have limitations.MethodsWe have developed a new model for estimating per-partnership chlamydia transmission probabilities from infected to uninfected individuals, using data from population-based surveys. We used data on sexual behaviour and prevalent chlamydia infection from the second UK National Study of Sexual Attitudes and Lifestyles (Natsal-2) and the US National Health and Nutrition Examination Surveys 2009-2014 (NHANES) for Bayesian inference of average transmission probabilities, across all new heterosexual partnerships reported. Posterior distributions were estimated by Markov chain Monte Carlo sampling using the Stan software.ResultsPosterior median male-to-female transmission probabilities per partnership were 32.1% [95% credible interval (CrI) 18.4-55.9%] (Natsal-2) and 34.9% (95%CrI 22.6-54.9%) (NHANES). Female-to-male transmission probabilities were 21.4% (95%CrI 5.1-67.0%) (Natsal-2) and 4.6% (95%CrI 1.0-13.1%) (NHANES). Posterior predictive checks indicated a well-specified model, although there was some discrepancy between reported and predicted numbers of partners, especially in women.ConclusionsThe model provides statistically rigorous estimates of per-partnership transmission probability, with associated uncertainty, which is crucial for modelling and understanding chlamydia epidemiology and control. Our estimates incorporate data from several sources, including population-based surveys, and use information contained in the correlation between number of partners and the probability of chlamydia infection. The evidence synthesis approach means that it is easy to include further data as it becomes available.

Project description:In the female genital ecosystem, the complex interplay between the host immune system and the resident microflora protects against urogenital pathogens, like Chlamydia trachomatisC. trachomatis is responsible for urethritis and cervicitis; however, most chlamydial infections are asymptomatic and, thus, not treated, potentially leading to severe reproductive sequelae. Here we investigated the interaction between the levels of selected immune mediators and the community state types of the cervical microbiota in C. trachomatis-infected women. Cervical samples from 42 C. trachomatis-positive women and 103 matched healthy controls were analyzed through the metagenomic analysis of the hypervariable region v4 of the 16S rRNA gene and the determination of lactoferrin, interleukin 1α (IL-1α), IL-6, alpha interferon (IFN-α), IFN-β, and IFN-γ by ELISA. Overall, C. trachomatis infection was significantly associated with a microbiota dominated by anaerobic bacteria (P = 0.000002). In addition, a network of Gardnerella vaginalis, Prevotella amnii, Prevotella buccalis, Prevotella timonensis, Aerococcus christensenii, and Variovorax guangxiensis has been identified as a potential biomarker of C. trachomatis infection through multiple statistical approaches. Again, chlamydial infection was significantly correlated with an increased production of lactoferrin, IL-6, IL-1α, IFN-α, and IFN-β (P < 0.05), whereas very low levels of IFN-γ were observed in C. trachomatis-infected women, levels similar to those detected in healthy women. Our findings show a distinctive signature of C. trachomatis genital infection, characterized by a specific bacterial network, constituted by anaerobes, as well as by increased levels of lactoferrin and proinflammatory cytokines (IL-1α, IL-6, IFN-α, and IFN-β), accompanied by low levels of IFN-γ.IMPORTANCE To our knowledge, this is the first study that investigated the association of C. trachomatis with the cervical levels of lactoferrin and selected inflammatory mediators and their correlation with the different community state types characterizing the female genital ecosystem. C. trachomatis, known as the leading cause of bacterial sexually transmitted diseases, continues to be an important public health problem worldwide for its increasing incidence and the risk of developing severe reproductive sequelae, like pelvic inflammatory disease and infertility. Specifically, C. trachomatis tend to persist in the female genital tract, leading to a chronic inflammatory state characterized by increased production of immune mediators responsible for tissue damage. Therefore, our study may help to broaden the knowledge on the complex interplay between the female genital microbiota and the host immune system in response to C. trachomatis infection.

Dataset Information

Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort.

Publications

Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort.

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