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

Abstract 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 s...

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Main Authors: Rina Kawahara, Takuma Fujii, Iwao Kukimoto, Hiroyuki Nomura, Rie Kawasaki, Eiji Nishio, Ryoko Ichikawa, Tetsuya Tsukamoto, Aya Iwata
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-80176-6
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author Rina Kawahara
Takuma Fujii
Iwao Kukimoto
Hiroyuki Nomura
Rie Kawasaki
Eiji Nishio
Ryoko Ichikawa
Tetsuya Tsukamoto
Aya Iwata
author_facet Rina Kawahara
Takuma Fujii
Iwao Kukimoto
Hiroyuki Nomura
Rie Kawasaki
Eiji Nishio
Ryoko Ichikawa
Tetsuya Tsukamoto
Aya Iwata
author_sort Rina Kawahara
collection DOAJ
description Abstract 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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spelling doaj.art-bc6024f673e74844b560dd2209d1aa592022-12-21T23:11:37ZengNature PortfolioScientific Reports2045-23222021-01-0111111210.1038/s41598-020-80176-6Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasiaRina Kawahara0Takuma Fujii1Iwao Kukimoto2Hiroyuki Nomura3Rie Kawasaki4Eiji Nishio5Ryoko Ichikawa6Tetsuya Tsukamoto7Aya Iwata8Department of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicinePathogen Genomics Center, National Institute of Infectious DiseasesDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Pathology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineAbstract 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.https://doi.org/10.1038/s41598-020-80176-6
spellingShingle Rina Kawahara
Takuma Fujii
Iwao Kukimoto
Hiroyuki Nomura
Rie Kawasaki
Eiji Nishio
Ryoko Ichikawa
Tetsuya Tsukamoto
Aya Iwata
Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
Scientific Reports
title Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
title_full Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
title_fullStr Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
title_full_unstemmed Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
title_short Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
title_sort changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia
url https://doi.org/10.1038/s41598-020-80176-6
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