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      Assessing the Cervicovaginal Microbiota in the Context of hrHPV Infections: Temporal Dynamics and Therapeutic Strategies

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          ABSTRACT

          Cervical cancer is the third leading cause of female cancers globally, resulting in more than 300,000 deaths every year. The majority of all cervical cancers are caused by persistent infections with high-risk human papillomaviruses (hrHPV) that can progress to cancer via a series of premalignant lesions. Most women, however, clear this infection within a year, concomitant with disease regression. Both hrHPV clearance and disease regression have been associated with the composition of the cervicovaginal microenvironment, which is defined by the host immune system and the cervicovaginal microbiome (CVM). A healthy microbiome is generally characterized by a high abundance of Lactobacillus species, and a change in the composition may cause bacterial vaginosis (BV), which is associated with an increased susceptibility to persistent hrHPV infections and disease. In this review, the composition of the CVM is discussed, with emphasis on the possible causes that drive changes in the cervicovaginal microbiota in relation to hrHPV infections, disease progression, and disease regression. The literature search focused on the composition of the CVM and its correlation with hrHPV infections and neoplastic lesions as well as the current efforts to adjust the microbiome against adverse viral outcomes.

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          Most cited references141

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          Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

          An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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            Vaginal microbiome of reproductive-age women.

            The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
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              The causal relation between human papillomavirus and cervical cancer.

              The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
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                Author and article information

                Contributors
                Role: Invited Editor
                Role: Editor
                Journal
                mBio
                mBio
                mbio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                18 August 2022
                Sep-Oct 2022
                18 August 2022
                : 13
                : 5
                : e01619-22
                Affiliations
                [a ] Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
                [b ] Department of Medical Microbiology, Radboud Institute for Molecular Life Sciencesgrid.461760.2, , Nijmegen, The Netherlands
                [c ] Department of Biochemistry, Radboud Institute for Molecular Life Sciencesgrid.461760.2, , Nijmegen, The Netherlands
                [d ] Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciencesgrid.461760.2, , Nijmegen, The Netherlands
                Tufts University School of Medicine
                Icahn School of Medicine at Mount Sinai
                Author notes

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0003-4260-0509
                https://orcid.org/0000-0001-6189-5491
                https://orcid.org/0000-0002-5446-2230
                Article
                01619-22 mbio.01619-22
                10.1128/mbio.01619-22
                9600249
                35980030
                78abc05e-6e76-4497-a3a4-39ea45ed7847
                Copyright © 2022 Molina et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                supplementary-material: 0, Figures: 3, Tables: 1, Equations: 0, References: 142, Pages: 15, Words: 11578
                Funding
                Funded by: Ruby and Rose Foundation;
                Award Recipient :
                Categories
                Minireview
                clinical-microbiology, Clinical Microbiology
                Custom metadata
                September/October 2022

                Life sciences
                microbiome,cervicovaginal microbiota,microbial communities,cvm,csts,human papillomavirus,hrhpv

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