The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis.
Lactobacilli
Cervical cancer
dysplasia
microbiome
vaginal microbiota
Journal
BJOG : an international journal of obstetrics and gynaecology
ISSN: 1471-0528
Titre abrégé: BJOG
Pays: England
ID NLM: 100935741
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
accepted:
07
06
2019
pubmed:
27
6
2019
medline:
6
2
2020
entrez:
26
6
2019
Statut:
ppublish
Résumé
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. To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862). PubMed, Web of science, Embase and Cochrane database. 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. 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. 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. 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. This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.
Sections du résumé
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 meta-analysis (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.
Identifiants
pubmed: 31237400
doi: 10.1111/1471-0528.15854
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
171-180Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Royal College of Obstetricians and Gynaecologists.
Références
Boris S, Barbés C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect 2000;2:543-6.
Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol 2001;185:375-9.
Brusselaers N, Shrestha S, van de Wijgert J, Verstraelen H. Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis. Am J Obstet Gynecol 2018; 221: 9-18. https://doi/10.1016/j.ajog.2018.12.011
Jacobsson B, Pernevi P, Chidekel L, Jörgen Platz-Christensen J. Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis. Acta Obstet Gynecol Scand 2002;81:1006-10.
Ness RB, Kip KE, Hillier SL, Soper DE, Stamm CA, Sweet RL, et al. A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol 2005;162:585-90.
Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14-22.
Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991;29:297-301.
Brotman RM, Shardell MD, Gajer P, Tracy JK, Zenilman JM, Ravel J, et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J Infect Dis 2014;210:1723-33.
Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, Lehne B, et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep 2015;5:16865.
Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 2011;108(Suppl 1):4680-7.
van de Wijgert JH, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H, et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One 2014;9:e105998.
Gillet E, Meys JF, Verstraelen H, Verhelst R, De Sutter P, Temmerman M, et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: systematic review and meta-analysis. PLoS One 2012;7:e45201.
Tamarelle J, Thiebaut ACM, de Barbeyrac B, Bebear C, Ravel J, Delarocque-Astagneau E. The vaginal microbiota and its association with human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections: a systematic review and meta-analysis. Clin Microbiol Infect 2019;25:35-47.
zur Hausen H. Viruses in human cancers. Eur J Cancer 1999;35:1878-85.
Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet 2013;382:889-99.
World Health Organization. Comprehensive Cervical Cancer Control: A Guide to Essential Practice, 2nd edn. Geneva: World Health Organization; 2014.
Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 2015;162:777-84.
AHRQ. Methodology checklist for cross-sectional study [www.ncbi.nlm.nih.gov/books/NBK35156/]. Accessed 11 November 2018.
Shim S, Yoon BH, Shin IS, Bae JM. Network meta-analysis: application and practice using Stata. Epidemiol Health 2017;39:e2017047.
Audirac-Chalifour A, Torres-Poveda K, Bahena-Roman M, Tellez-Sosa J, Martinez-Barnetche J, Cortina-Ceballos B, et al. Cervical microbiome and cytokine profile at various stages of cervical cancer: a pilot study. PLoS One 2016;11:e0153274.
Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J 2014;8:1781-93.
Dareng EO, Ma B, Famooto AO, Adebamowo SN, Offiong RA, Olaniyan O, et al. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect 2016;144:123-37.
Di Paola M, Sani C, Clemente AM, Iossa A, Perissi E, Castronovo G, et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk human papillomavirus infection. Sci Rep 2017;7:10200.
Dols JA, Reid G, Kort R, Schuren FH, Tempelman H, Bontekoe TR, et al. PCR-based identification of eight Lactobacillus species and 18 hr-HPV genotypes in fixed cervical samples of South African women at risk of HIV and BV. Diagn Cytopathol 2012;40:472-7.
Gao W, Weng J, Gao Y, Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis 2013;13:271.
Seo SS, Oh HY, Lee JK, Kong JS, Lee DO, Kim MK. Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia. Clin Nutr 2016;35:1434-41.
Shannon B, Yi TJ, Perusini S, Gajer P, Ma B, Humphrys MS, et al. Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol 2017;10:1310-9.
Zhang CT, Liu Y, Gao WJ, Pan YQ, Gao YN, Shen J, et al. The direct and indirect association of cervical microbiota with the risk of cervical intraepithelial neoplasia. Cancer Med 2018;7:2172-9.
Arokiyaraj S, Seo SS, Kwon M, Lee JK, Kim MK. Association of cervical microbial community with persistence, clearance and negativity of human papillomavirus in Korean women: a longitudinal study. Sci Rep 2018;8:15479.
Dareng EO, Famooto AO, Ogbonna CC, Akarolo-Anthony S, Al-Mujtaba M, Odonye G, et al. Increased risk of prevalent high risk human papillomavirus infection in Lactobacillus iners rich microbiota in Nigerian women. Can Res 2013;73(8 Suppl). https://doi.org/10.1158/1538-7445.AM2013-2588.
Godoy-Vitorino F, Romaguera J, Zhao C, Vargas-Robles D, Ortiz-Morales G, Vazquez-Sanchez F, et al. Cervicovaginal fungi and bacteria associated with cervical intraepithelial neoplasia and high-risk human papillomavirus infections in a Hispanic population. Front Microbiol 2018;9:2533.
Huang XJ, Li C, Li F, Zhao JW, Wan XP, Wang K. Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types. Int J Cancer 2018;143:621-34.
Kwasniewski W, Wolun-Cholewa M, Kotarski J, Warchol W, Kuzma D, Kwasniewska A, et al. Microbiota dysbiosis is associated with HPV-induced cervical carcinogenesis. Oncol Lett 2018;16:7035-47.
Lam KC, Vyshenska D, Hu J, Rodrigues RR, Nilsen A, Zielke RA, et al. Transkingdom network reveals bacterial players associated with cervical cancer gene expression program. PeerJ 2018;6:e5590.
Laniewski P, Barnes D, Goulder A, Cui H, Monk B, Greenspan D, et al. Does vaginal microbiome composition alter local cancer biomarker expression in cervical dysplasia and cancer? Int J Gynecol Cancer 2018;28:157.
Laniewski P, Barnes D, Goulder A, Cui HY, Roe DJ, Chase DM, et al. Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women. Sci Rep 2018;8:7593.
Lee JE, Lee S, Lee H, Song YM, Lee K, Han MJ, et al. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort. PLoS One 2013;8:e63514.
Oh HY, Kim BS, Seo SS, Kong JS, Lee JK, Park SY, et al. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea. Clin Microbiol Infect 2015;21:674.e1-9.
Piyathilake CJ, Ollberding NJ, Kumar R, Macaluso M, Alvarez RD, Morrow CD. Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses. Cancer Prev Res (Phila) 2016;9:357-66.
Reimers LL, Mehta SD, Massad LS, Burk RD, Xie X, Ravel J, et al. The cervicovaginal microbiota and its associations with human papillomavirus detection in HIV-infected and HIV-uninfected women. J Infect Dis 2016;214:1361-9.
Ritu W, Enqi W, Zheng S, Wang J, Ling Y, Wang Y. Evaluation of the associations between cervical microbiota and HPV infection, clearance, and persistence in cytologically normal women. Cancer Prev Res (Phila) 2019;12:43-56.
Schmidt K, Cybulski Z, Roszak A, Grabiec A, Talaga Z, Urbanski B, et al. Combination of microbiological culture and multiplex PCR increases the range of vaginal microorganisms identified in cervical cancer patients at high risk for bacterial vaginosis and vaginitis. Ginekol Pol 2015;86:328-34.
Wang PC, Song JH. The correlation between vaginal microecological changes and HPV outcome in patients with cervical lesions in the Inner Mongolia area of China. Int J Clin Exp Med 2017;10:5711-20.
Feng RM, Wang MZ, Smith JS, Dong L, Chen F, Pan QJ, et al. Risk of high-risk human papillomavirus infection and cervical precancerous lesions with past or current trichomonas infection: a pooled analysis of 25,054 women in rural China. J Clin Virol 2018;99-100:84-90.
Smith BC, McAndrew T, Chen Z, Harari A, Barris DM, Viswanathan S, et al. The cervical microbiome over 7 years and a comparison of methodologies for its characterization. PLoS One 2012;7:e40425.
Clarke MA, Rodriguez AC, Gage JC, Herrero R, Hildesheim A, Wacholder S, et al. A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection. BMC Infect Dis 2012;12:33.
Nunn KL, Wang YY, Harit D, Humphrys MS, Ma B, Cone R, et al. Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota. Mbio 2015;6:e01084-15.
Witkin SS. The vaginal microbiome, vaginal anti-microbial defence mechanisms and the clinical challenge of reducing infection-related preterm birth. BJOG 2015;122:213-8.
Tachedjian G, O'Hanlon DE, Ravel J. The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota. Microbiome 2018;6:29.
Marchesi JR, Dutilh BE, Hall N, Peters WH, Roelofs R, Boleij A, et al. Towards the human colorectal cancer microbiome. PLoS One 2011;6:e20447.
Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013;14:207-15.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013;342:971-6.
Machado A, Cerca N. Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis. J Infect Dis 2015;212:1856-61.
Swidsinski A, Mendling W, Loening-Baucke V, Ladhoff A, Swidsinski S, Hale LP, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005;106:1013-23.
Swidsinski A, Loening-Baucke V, Mendling W, Dörffel Y, Schilling J, Halwani Z, et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol Histopathol 2014;29:567-87.
Anahtar MN, Byrne EH, Doherty KE, Bowman BA, Yamamoto HS, Soumillon M, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity 2015;42:965-76.
Rajamanoharan S, Low N, Jones SB, Pozniak AL. Bacterial vaginosis, ethnicity, and the use of genital cleaning agents: a case control study. Sex Transm Dis 1999;26:404-9.