Cervicovaginal microbiome and natural history of HPV in a longitudinal study

Usyk, Mykhaylo; Zolnik, Christine P.; Castle, Philip E.; Porras, Carolina; Herrero, Rolando; Gradíssimo, Ana; González, Paula; Safaeian, Mahboobeh; Schiffman, Mindy R.; Burk, Robert D.

doi:10.1371/journal.ppat.1008376

Cited by 174 publications

(167 citation statements)

References 73 publications

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“…That means the decrease of the relative abundance level of L. gallinarum and the increase of the relative abundance level of L. iners might be associated with the decline of ovarian function. However, According to previous studies, the role of L. iners is contextual in different populations and the clinical conditions of HPV infection [38,39]. Therefore, its effect on the host warrants further study under a variety of health conditions.…”

Section: Discussionmentioning

confidence: 98%

Changes in the vaginal microbiota associated with primary ovarian failure

Wang

Han

et al. 2020

BMC Microbiol

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Background: Primary ovarian failure (POF) is defined as follicular failure in women of reproductive age. Although many factors are speculated to contribute to the occurrence of POF, the exact aetiology remains unclear. Moreover, alterations in the microbiome of patients with POF are poorly studied. Results: This study investigated the vaginal microbiota of 22 patients with POF and 29 healthy individuals. Highthroughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to evaluate the relationships between the vaginal flora and clinical characteristics of POF. Different from results of previous studies, we found that the diversity and richness of the vaginal flora of patients with POF was significantly different from those of healthy controls. Comparison of the vaginal flora of patients with POF with that of menopausal women revealed that the relative abundance of Lactobacillus was significantly reduced in the latter. A reduced abundance of Lactobacillus was furthermore associated with a lower pregnancy success rate. Of particular interest is that L. gallinarum especially appeared to be beneficially associated with reproductive-related indicators (FSH, E2, AMH, PRL) whilst L. iners appeared to have a detrimental effect. The result of the present study may enable the identification of microbiota associated with POF, however, further investigations of differences in the microbiota in the context of POF will enable a deeper understanding of the disease pathogenesis that involves modification of the vaginal microbiota. Conclusions: The present study identified the microbiota associated with POF. Further investigations on the differences in the microbiota in the context of POF will improve our understanding of the pathogenesis of the disease which involves modification of the vaginal microbiota.

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Section: Discussionmentioning

confidence: 98%

Changes in the vaginal microbiota associated with primary ovarian failure

Wang

Han

et al. 2020

BMC Microbiol

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“…Local interplay between the microbiome and the immune response may be important for understanding the pathogenesis of the sequence of events from HPV infection, CIN development and progression to cervical cancer 8 . As one approach to investigating this issue, we examined how removal of the neoplastic lesions by surgery impacted on associations between microbiome diversity, local immune responses and the number of HPV genotypes in patients with CIN.…”

Section: Discussionmentioning

confidence: 99%

Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia

Kawahara

Fujii

Kukimoto

et al. 2021

Sci Rep

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Persistent HPV infection associated with immune modulation may result in high-grade squamous intraepithelial lesions (CIN)2/3. Currently, there is little information on the cervicovaginal microbiome, local cytokine levels and HPV infection related to CIN. Follow-up of patients after local surgery provides an opportunity to monitor changes in the cervicovaginal environment. Accordingly, we undertook this longitudinal retrospective study to determine associations between HPV genotypes, cervicovaginal microbiome and local cytokine profiles in 41 Japanese patients with CIN. Cervicovaginal microbiota were identified using universal 16S rRNA gene (rDNA) bacterial primers for the V3/4 region by PCR of genomic DNA, followed by MiSeq sequencing. We found that Atopobium vaginae was significantly decreased (p < 0.047), whereas A. ureaplasma (p < 0.022) increased after surgery. Cytokine levels in cervical mucus were measured by multiplexed bead-based immunoassays, revealing that IL-1β (p < 0.006), TNF-α (p < 0.004), MIP-1α (p < 0.045) and eotaxin (p < 0.003) were significantly decreased after surgery. Notably, the level of eotaxin decreased in parallel with HPV clearance after surgery (p < 0.028). Thus, local surgery affected the cervicovaginal microbiome, status of HPV infection and immune response. Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia may be important for understanding the pathogenesis of CIN in future.

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“…Further viral and cellular proteins might be excellent candidate indicators of disease, e.g., HPV L1 protein, Claudin-1, VCP, and E-cadherin, which have promising results in research [190][191][192][193][194]. Alternatively, the vaginal microbiome might be used to distinguish progression vs. regression of disease [195][196][197]. The overall results from existing and candidate biomarkers evidence their utility in profiling the risk for disease.…”

Section: Resultsmentioning

confidence: 99%

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

Molina

Diatricch

Quintana

et al. 2020

Expert Review of Molecular Diagnostics

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Introduction: Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. Areas covered: We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. Expert opinion: Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.

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Cervicovaginal microbiome and natural history of HPV in a longitudinal study

Cited by 174 publications

References 73 publications

Changes in the vaginal microbiota associated with primary ovarian failure

Changes in the vaginal microbiota associated with primary ovarian failure

Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

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