Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population

Godoy-Vitorino, Filipa; Romaguera, Josefina; Zhao, Chunyu; Vargas-Robles, Daniela; Ortiz-Morales, Gilmary; Vázquez-Sánchez, Frances; Sánchez-Vázquez, María M.; Garza-Casillas, Manuel de la; Martínez‐Ferrer, Magaly; White, James R.; Bittinger, Kyle; Domínguez-Bello, María Gloria; Blaser, Martin J.

doi:10.3389/fmicb.2018.02533

Cited by 82 publications

(112 citation statements)

References 93 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

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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

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“…In summary, through the use of longitudinal samples from the CVT cohort we investigated and identified key features of the cervicovaginal microbiome potentially associated with progression of HR-HPV infection [28, [53][54][55][56] (e.g., Gardnerella and subsequent increase vaginal microbial diversity). Additional studies are required to validate the model proposed in this report.…”

Section: Plos Pathogensmentioning

confidence: 99%

Cervicovaginal microbiome and natural history of HPV in a longitudinal study

et al. 2020

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BackgroundHuman papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV. MethodsThis study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R. ResultsAt Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was PLOS PATHOGENS PLOS Pathogens | https://doi.

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“…Discoveries resulting from human microbiome research have demonstrated that microbes play a role in the susceptibility to HPV and neoplasia [1][2][3]. Oncogenic high-risk human papilloma virus (HPV+H) infections are associated with the development of carcinomas, a malignancy on the rise in multiple populations [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…In Mexican women, Sneathia spp. were considered cervical biomarkers for neoplasia [14], while in Puerto Ricans, a loss in Lactobacillus was associated with an increase in Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions with HPV+H, low-risk HPV, or both co-infections [2]. Cervical microbiota of a majority of HIV negative black South African women was not dominated by Lactobacillus, suggesting that such cervical microbiota may be a contributing factor to the high burden of HIV and HPV infections among black women [15].…”

Section: Introductionmentioning

confidence: 99%

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Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

2020

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In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity.

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Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population

Cited by 82 publications

References 93 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

Cervicovaginal microbiome and natural history of HPV in a longitudinal study

Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

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