Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women

Łaniewski, Paweł; Barnes, Dominique; Goulder, Alison; Cui, Haiyan; Roe, Denise J.; Chase, Dana M.; Herbst-Kralovetz, Melissa M.

doi:10.1038/s41598-018-25879-7

Cited by 189 publications

(371 citation statements)

References 54 publications

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“…Our systematic search resulted in 11 eligible included articles (Figure ), of which the general characteristics and quality assessment are described in the Supplementary material (Tables S2 and S3). Reasons for exclusion of the articles excluded after full text screening are reported in the Supplementary material (Appendix S2), with 15 studies lacking essential data for inclusion in the network meta‐analysis …”

Section: Resultsmentioning

confidence: 99%

The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis

Norenhag

Olovsson

et al. 2019

BJOG

249

219

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Background Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.Objective To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network metaanalysis (registered in PROSPERO: CRD42018112862).Search strategy PubMed, Web of science, Embase and Cochrane database.Selection criteria All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.Data collection and analysis For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.Main results Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.Conclusions These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.Tweetable abstract This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.

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Section: Resultsmentioning

confidence: 99%

The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis

Norenhag

Olovsson

et al. 2019

BJOG

249

219

View full text Add to dashboard Cite

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“…In this scenario, Hispanic ethnicity by itself was associated with a decrease in Lactobacillus dominance and Sneathia spp. enrichment when compared to non-Hispanic women living in the U.S [102].…”

Section: Microbiota As a Biomarker For Hpv And Cervical Dysplasiamentioning

confidence: 96%

“…Likewise, Lactobacillus dominance decreased together with cervical dysplasia severity while Sneathia spp. were increased in low/ high grade precancerous lesions and invasive cervical carcinoma [102]. In this context, different analyses suggest a paucity of Lactobacillus and increased relative abundance of other species as a factor associated with cervical abnormality development.…”

Section: Microbiota As a Biomarker For Hpv And Cervical Dysplasiamentioning

confidence: 97%

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

Curty

Carvalho

Soares

2019

IJMS

120

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The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.

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“…Recently, our laboratory measured increased levels of IL-36γ in cervicovaginal lavages (CVLs) from cervical cancer patients [30]. Additionally, clinical proteomic studies have also measured an increase in the relative abundance of IL-36γ in CVLs from HSV-2 seropositive Depo-Provera users [31], and an increase in IL-36 cytokines in women with bacterial vaginosis [32].…”

Section: Introductionmentioning

confidence: 99%

IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis

Gardner

Herbst-Kralovetz

2018

Cytokine

Self Cite

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Herpes simplex virus 2 (HSV-2) causes a persistent, lifelong infection that increases risk for sexually transmitted infection acquisition. Both the lack of a vaccine and the need for chronic suppressive therapies to control infection presents the need to further understand immune mechanisms in response to acute HSV-2 infection. The IL-36 cytokines are recently identified members of the IL-1 family and function as inflammatory mediators at epithelial sites. Here, we first used a well-characterized three-dimensional (3-D) human vaginal epithelial cell (VEC) model to understand the role of IL-36γ in the context of HSV-2 infection. In 3-D VEC, IL-36γ is induced by HSV-2 infection, and pretreatment with exogenous IL-36γ significantly reduced HSV-2 replication. To assess the impact of IL-36γ treatment on HSV-2 disease pathogenesis, we employed a lethal genital infection model. We showed that IL-36γ treatment in mice prior to lethal intravaginal challenge significantly limited vaginal viral replication, delayed disease onset, decreased disease severity, and significantly increased survival. We demonstrated that IL-36γ treatment transiently induced pro-inflammatory cytokines, chemokines, and antimicrobial peptides in murine lower female reproductive tract (FRT) tissue and vaginal lavages. Induction of the chemokines CCL20 and KC in IL-36γ treated mice also corresponded with increased polymorphonuclear (PMN) leukocyte infiltration observed in vaginal smears. Altogether, these studies demonstrate that IL-36γ drives the transient production of immune mediators and promotes PMN recruitment in the vaginal microenvironment that increases resistance to HSV-2 infection and disease. Our data indicate that IL-36γ may participate as a key player in host defense mechanisms against invading pathogens in the FRT.

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Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women

Cited by 189 publications

References 54 publications

The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis

The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis

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