Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2023; 83(08): 1017-1021
DOI: 10.1055/a-2044-0162
GebFra Science
Review

Dysbiotic Co-Factors in Cervical Cancer. How the Microbiome Influences the Development of Cervical Intraepithelial Neoplasia (CIN)

Article in several languages: English | deutsch
Patrick Finzer
1   dus.ana Düsseldorf Analytik, Praxis für medizinische Mikrobiologie und Laboratoriumsmedizin, Düsseldorf, Germany
2   Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany (Ringgold ID: RIN9170)
,
Volkmar Küppers
3   Zytologisches Labor, Dysplasie-Sprechstunde, Praxis für Frauenheilkunde & Geburtshilfe, Düsseldorf, Germany
,
Henrik Griesser
4   Fachabteilung Pathologie und Zytodiagnostik, Labor Dr. Wisplinghoff, Köln, Germany
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Human papillomavirus (HPV) infection is a necessary but not sufficient condition for the development of cervical cancer. The dysbiotic shift in the cervicovaginal microbiome appears to be a major co-factor in carcinogenesis. New analytical methods, such as next-generation sequencing (NGS), can be used to detect all of the vaginal microorganisms present and therefore identify individual therapeutic options. The relationship of bacterial vaginosis and carcinogenesis, as well as possible indications for the use of microbiome analysis, will be discussed.

Keywords

vaginal microbiome - HPV infection - CIN lesion


Publication History

Received: 09 December 2022

Accepted after revision: 20 February 2023

Article published online:
04 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References/Literatur

  • 1 Beckmann MW, Stübs FA, Koch MC. et al. Diagnosis, therapy and follow-up of cervical cancer. Guideline of the DGGG, DKG and DKH (S3-level, AWMF registry No. 032/O33OL, May 2021) – Part 1 with recommendations on epidemiology, screening, diagnostics and therapy. Geburtshilfe Frauenheilkd 2022; 82: 139-180
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Wilting SM, Steenbergen RDM. Molecular events leading to HPV-induced high-grade neoplasia. Papillomavirus Res 2016; 2: 85-88
    CrossrefPubMedSearch in Google Scholar
  • 3 Plummer M, Schiffman M, Castle PE. et al. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 2007; 195: 1582-1589
    CrossrefPubMedSearch in Google Scholar
  • 4 Guijon F, Paraskevas M, Rand F. et al. Vaginal microbial flora as a cofactor in the pathogenesis of uterine cervical intraepithelial neoplasia. Int J Gynaecol Obstet 1992; 37: 185-191
    CrossrefPubMedSearch in Google Scholar
  • 5 Mendling W. Die bakterielle Vaginose – nach 60 Jahren immer noch ein Rätsel. Frauenarzt 2017; 58: 225-228
    PubMedSearch in Google Scholar
  • 6 Gillet E, Meys JFA, Verstraelen H. et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: systematic review and meta-analysis. PLoS One 2012; 7: e45201
    CrossrefPubMedSearch in Google Scholar
  • 7 Liang Y, Chen M, Qin L. et al. A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia. Infect Agent Cancer 2019; 14: 29
    CrossrefPubMedSearch in Google Scholar
  • 8 Mendling W. Diagnostik und Therapie beim Symptom Fluor. Frauenarzt 2018; 59: 120-128
    PubMedSearch in Google Scholar
  • 9 Curry KD, Wang Q, Nute MG. et al. Emu: species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data. Nat Methods 2022; 19: 845-853
    CrossrefPubMedSearch in Google Scholar
  • 10 Ravel J, Gajer P, Abdo Z. et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108 (Suppl. 01) 4680-4687
    CrossrefPubMedSearch in Google Scholar
  • 11 France MT, Ma B, Gajer P. et al. VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition. Microbiome 2020; 8: 166
    CrossrefPubMedSearch in Google Scholar
  • 12 Symul L, Jeganathan P, Costello EK. et al. Sub-communities of the vaginal ecosystem in pregnant and non-pregnant women. bioRxiv 2022;
    CrossrefPubMedSearch in Google Scholar
  • 13 Petrova MI, Reid G, Vaneechoutte M. et al. Lactobacilllus iners: Friend or Foe?. Trends Microbiol 2017; 25: 182-191
    CrossrefPubMedSearch in Google Scholar
  • 14 Lin D, Kouzy R, Jaoude JA. et al. Microbiome factors in HPV-driven carcinogenesis and cancers. PLoS Pathog 2020; 16: e1008524
    CrossrefPubMedSearch in Google Scholar
  • 15 Di Paolo M, Sani C, Clemente AM. et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk human papillomavirus infection. Sci Rep 2017; 7: 10200
    CrossrefPubMedSearch in Google Scholar
  • 16 Brotman RM, Shardell MD, Gajer P. et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J Infect Dis 2014; 210: 1723-1733
    CrossrefPubMedSearch in Google Scholar
  • 17 Mitra A, MacIntyre DA, Lee YS. et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep 2015; 5: 16865
    CrossrefPubMedSearch in Google Scholar
  • 18 Usyk M, Zolnik CP, Castle PE. et al. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog 2020; 16: e1008376
    CrossrefPubMedSearch in Google Scholar
  • 19 Piyathilake CJ, Ollberding NJ, Kumar R. et al. Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses. Cancer Prev Res (Phila) 2016; 9: 357-366
    CrossrefPubMedSearch in Google Scholar
  • 20 Dai W, Du H, Li S. et al. Cervicovaginal microbiome factors in clearance of human papillomavirus infection. Front Oncol 2021; 11: 722639
    CrossrefPubMedSearch in Google Scholar
  • 21 Witkin SS, Mendes-Soares H, Linhares IM. et al. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections. mBio 2013; 4: e00460–13
    CrossrefPubMedSearch in Google Scholar
  • 22 Nunn KL, Wang YY, Harit D. et al. Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with lactobacillus crispatus-dominant microbiota. mBio 2015; 6 -e01084–15
    CrossrefPubMedSearch in Google Scholar
  • 23 Mitra A, MacIntyre DA, Marches JR. et al. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?. Microbiome 2016; 4: 58
    CrossrefPubMedSearch in Google Scholar
  • 24 Mitchel C, Marrazzo J. Bacterial vaginosis and the cervicovaginal immune response. Am J Reprod Immunol 2014; 71: 555-563
    CrossrefPubMedSearch in Google Scholar
  • 25 Paavonen J, Brunham RC. Bacterial vaginosis and desquamative inflammatory vaginitis. N Engl J Med 2018; 379: 2246-2254
    CrossrefPubMedSearch in Google Scholar
  • 26 Cohen CR, Wierzbicki MR, French AL. et al. Randomized trial of lactin-V to prevent recurrence of bacterial vaginosis. N Engl J Med 2020; 382: 1906-1915
    CrossrefPubMedSearch in Google Scholar
  • 27 Liu HF, Yi N. A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis. Eur Rev Med Pharmacol Sci 2022; 26: 90-98
    CrossrefPubMedSearch in Google Scholar
  • 28 Jahanshahi M, Dana PM, Badehnoosh B. et al. Anti-tumor activities of probiotics in cervical cancer. J Ovarian Res 2020; 13: 68
    CrossrefPubMedSearch in Google Scholar
  • 29 Verhoeven V, Renard N, Makar A. et al. Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study. Eur J Cancer Prev 2013; 22: 46-51
    CrossrefPubMedSearch in Google Scholar
  • 30 Rousseau V, Lepargneur JP, Roques C. et al. Prebiotic effects of oligosaccharides on selected vaginal lactobacilli and pathogenic microorganisms. Anaerobe 2005; 11: 145-153
    CrossrefPubMedSearch in Google Scholar
  • 31 Mistry N, Drobni P, Näslund J. et al. The anti-papillomavirus activity of human and bovine lactoferricin. Antiviral Res 2007; 75: 258-265
    CrossrefPubMedSearch in Google Scholar
  • 32 Pino A, Giunta G, Randazzo CL. et al. Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial. Microb Ecol Health Dis 2017; 28: 1357417
    CrossrefPubMedSearch in Google Scholar
  • 33 Wang H, Ma Y, Li R. et al. Associations of cervicovaginal lactobacilli with high-risk human papillomavirus infection, cervical intraepithelial neoplasia, and cancer: A systematic review and meta-analysis. J Infect Dis 2019; 220: 1243-1254
    CrossrefPubMedSearch in Google Scholar