Co-Expression of HSV2 and &lt;i&gt;Chlamydia trachomatis&lt;/i&gt; in HPV-Positive Cervical Cancer and Cervical Intraepithelial Neoplasia Lesions Is Associated with Aberrations in Key Intracellular Pathways

Paba, Pierpaolo; Bonifacio, Daniela; Bonito, Luigi Di; Ombres, Domenico; Favalli, Cartesio; Syrjänen, Karí; Ciotti, Marco

doi:10.1159/000156481

Cited by 61 publications

(61 citation statements)

References 54 publications

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“…Like other sexually transmitted genital pathogens, Mycoplasma spp. may be associated with changes in epithelial cells that facilitate entry of HPV virions or with changes in the immunological response pathways that decrease the host’s ability to resolve HPV infection (39, 40). Several bacteria, particularly those capable of establishing persistent infections, can alter host cell cycles, affect apoptotic pathways, and stimulate the production of inflammatory substances linked to DNA damage, thus potentially promote abnormal cell growth (12).…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Adebamowo

Zella

et al. 2017

Front. Public Health

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BackgroundRecent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections.MethodsWe examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections.ResultsThe mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008), compared to women who were negative for both.ConclusionWe found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Adebamowo

Zella

et al. 2017

Front. Public Health

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“…Persistent, high-risk HPV infections are more likely to progress to squamous cell carcinoma (SCC) or invasive cervical cancer (ICC) in the presence of identified cofactors including smoking, behavioral factors, age, genetic background and individual immune variation 27. Chronic cervical infection by C. trachomatis has been proposed as a cofactor based on detection of chlamydial DNA in HPV-associated lesions 28 and studies correlating the presence of anti-CT antibodies with risk for ICC or SCC 29. A recent meta analysis of 22 studies (19 retrospective, 3 prospective) determined that C. trachomatis was significantly linked to increased cervical cancer risk prospectively (OR = 2.21, 95% CI: 1.88-2.61, P < 0.001), and retrospectively (OR = 2.19, 95% CI: 1.74-2.74, P < 0.001) 30.…”

Section: Genitourinary Tract Infeciton Disease and Reproductive Sequmentioning

confidence: 99%

Chlamydia trachomatis Genital Infections

O’Connell¹,

Ferone²

2016

MIC

174

153

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Etiology, transmission and protection: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infection (STI) globally. However, C. trachomatis also causes trachoma in endemic areas, mostly Africa and the Middle East, and is a leading cause of preventable blindness worldwide. Epidemiology, incidence and prevalence: The World Health Organization estimates 131 million new cases of C. trachomatis genital infection occur annually. Globally, infection is most prevalent in young women and men (14-25 years), likely driven by asymptomatic infection, inadequate partner treatment and delayed development of protective immunity. Pathology/Symptomatology: C. trachomatis infects susceptible squamocolumnar or transitional epithelial cells, leading to cervicitis in women and urethritis in men. Symptoms are often mild or absent but ascending infection in some women may lead to Pelvic Inflammatory Disease (PID), resulting in reproductive sequelae such as ectopic pregnancy, infertility and chronic pelvic pain. Complications of infection in men include epididymitis and reactive arthritis. Molecular mechanisms of infection: Chlamydiae manipulate an array of host processes to support their obligate intracellular developmental cycle. This leads to activation of signaling pathways resulting in disproportionate influx of innate cells and the release of tissue damaging proteins and pro-inflammatory cytokines. Treatment and curability: Uncomplicated urogenital infection is treated with azithromycin (1 g, single dose) or doxycycline (100 mg twice daily x 7 days). However, antimicrobial treatment does not ameliorate established disease. Drug resistance is rare but treatment failures have been described. Development of an effective vaccine that protects against upper tract disease or that limits transmission remains an important goal.

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“…In addition, we found that women with C. trachomatis have a 2.7 higher chance of presenting multiple infections than a single infection by HPV, although this result was not statistically significant in this sample size (OR, 2.7; 95% CI, 0.8-9.0). Similarly, Paba and colleagues (32) demonstrated that the risk of a woman presenting an infection due to two concomitant types of HPV is 7.2 times higher in the presence of C. trachomatis. One large longitudinal study also showed that prior infection by C. trachomatis is the greatest risk factor for the persistence of HPV DNA (33).…”

Section: Discussionmentioning

confidence: 91%

“…The presence of genital infection is increasingly considered as a risk factor for the persistence of HPV infection and progression of the associated lesions, and the mechanisms of these associations have been the object of various studies (31)(32)(33)(34). In conventional Pap smears, Matheus and colleagues (12) showed a high expression of MMP-9 in the presence of genital infections.…”

Section: Discussionmentioning

confidence: 99%

MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis

Discacciati

Gimenes

Pennacchi

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis.Methods: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/ CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR.

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Co-Expression of HSV2 and <i>Chlamydia trachomatis</i> in HPV-Positive Cervical Cancer and Cervical Intraepithelial Neoplasia Lesions Is Associated with Aberrations in Key Intracellular Pathways

Cited by 61 publications

References 54 publications

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Chlamydia trachomatis Genital Infections

MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis

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