Vaginal Bacteria and Risk of Incident and Persistent Infection With High-Risk Subtypes of Human Papillomavirus: A Cohort Study Among Kenyan Women.
Journal
Sexually transmitted diseases
ISSN: 1537-4521
Titre abrégé: Sex Transm Dis
Pays: United States
ID NLM: 7705941
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
pubmed:
22
12
2020
medline:
13
7
2021
entrez:
21
12
2020
Statut:
ppublish
Résumé
Bacterial vaginosis (BV) is associated with an increased risk of high-risk human papillomavirus (hrHPV), whereas Lactobacillus-dominated vaginal microbiotas are associated with reduced burden of hrHPV. Few epidemiologic studies have prospectively investigated the relationships between vaginal bacteria and hrHPV, particularly among women from countries in Africa. We conducted a prospective cohort study nested within the Preventing Vaginal Infections trial to evaluate associations between vaginal bacteria and hrHPV incidence and persistence. Sexually active, HIV-seronegative women aged 18 to 45 years who had a vaginal infection at screening were eligible to enroll. Analyses were restricted to participants enrolled in Kenya and randomized to placebo. At enrollment and months 2, 4, 6, 8, 10, and 12, hrHPV testing, quantitative polymerase chain reaction (measuring taxon quantity per swab), and 16S rRNA gene amplicon sequencing of the vaginal microbiota were performed. Generalized estimating equations multinomial logistic regression models were fit to evaluate associations between vaginal bacteria and incident and persistent hrHPV. Eighty-four participants were included in this analysis. Higher concentrations of Lactobacillus crispatus were inversely associated with persistent hrHPV detection. Specifically, 1 tertile higher L. crispatus concentration was associated with 50% reduced odds of persistent hrHPV detection (odds ratio, 0.50; 95% confidence interval, 0.29-0.85). This study is consistent with reports that vaginal L. crispatus is associated with reduced susceptibility to hrHPV persistence. Evidence from in vitro studies provides insight into potential mechanisms by which L. crispatus may mediate hrHPV risk. Future studies should further explore in vivo mechanisms that may drive this relationship and opportunities for intervention.
Sections du résumé
BACKGROUND
Bacterial vaginosis (BV) is associated with an increased risk of high-risk human papillomavirus (hrHPV), whereas Lactobacillus-dominated vaginal microbiotas are associated with reduced burden of hrHPV. Few epidemiologic studies have prospectively investigated the relationships between vaginal bacteria and hrHPV, particularly among women from countries in Africa.
METHODS
We conducted a prospective cohort study nested within the Preventing Vaginal Infections trial to evaluate associations between vaginal bacteria and hrHPV incidence and persistence. Sexually active, HIV-seronegative women aged 18 to 45 years who had a vaginal infection at screening were eligible to enroll. Analyses were restricted to participants enrolled in Kenya and randomized to placebo. At enrollment and months 2, 4, 6, 8, 10, and 12, hrHPV testing, quantitative polymerase chain reaction (measuring taxon quantity per swab), and 16S rRNA gene amplicon sequencing of the vaginal microbiota were performed. Generalized estimating equations multinomial logistic regression models were fit to evaluate associations between vaginal bacteria and incident and persistent hrHPV.
RESULTS
Eighty-four participants were included in this analysis. Higher concentrations of Lactobacillus crispatus were inversely associated with persistent hrHPV detection. Specifically, 1 tertile higher L. crispatus concentration was associated with 50% reduced odds of persistent hrHPV detection (odds ratio, 0.50; 95% confidence interval, 0.29-0.85).
CONCLUSIONS
This study is consistent with reports that vaginal L. crispatus is associated with reduced susceptibility to hrHPV persistence. Evidence from in vitro studies provides insight into potential mechanisms by which L. crispatus may mediate hrHPV risk. Future studies should further explore in vivo mechanisms that may drive this relationship and opportunities for intervention.
Identifiants
pubmed: 33346587
doi: 10.1097/OLQ.0000000000001343
pii: 00007435-202107000-00008
pmc: PMC8184569
mid: NIHMS1652659
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-507Subventions
Organisme : NIAID NIH HHS
ID : R01 AI099106
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007140
Pays : United States
Informations de copyright
Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest and Sources of Funding: J.E.B. has received honoraria from Lupin Pharmaceuticals and BD for consulting. R.S.M. has received research funding, paid to the University of Washington, from Hologic Corporation and has received honoraria for consulting from Lupin Pharmaceuticals. S.S. has received consulting honoraria from Lupin Pharmaceuticals. D.N.F. and T.L.F. received a royalty from BD. All other authors declare that they do not have any conflicts of interest.
Références
Bosch FX, Burchell AN, Schiffman M, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine 2008; 26:K1–K16.
de Sanjosé S, Diaz M, Castellsagué X, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: A meta-analysis. Lancet Infect Dis 2007; 7:453–459.
Arbyn M, Castellsagué X, de Sanjosé S, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol 2011; 22:2675–2686.
Gao W, Weng J, Gao Y, et al. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: A cross-sectional study. BMC Infect Dis 2013; 13:271.
Lee JE, Lee S, Lee H, et al. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort. PLoS One 2013; 8:e63514.
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: jiu330.
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.
Audirac-Chalifour A, Torres-Poveda K, Bahena-Román M, et al. Cervical microbiome and cytokine profile at various stages of cervical cancer: A pilot study. PLoS One 2016; 11:e0153274.
Dareng EO, Ma B, Famooto AO, et al. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect 2016; 144:123–137.
Reimers LL, Mehta SD, Massad LS, et al. The cervicovaginal microbiota and its associations with human papillomavirus detection in HIV-infected and HIV-uninfected women. J Infect Dis 2016; 214:1361–1369.
Seo S-S, Oh HY, Lee J-K, et al. Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia. Clin Nutr 2016; 35:1434–1441.
Di Paola 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.
Kero K, Rautava J, Syrjänen K, et al. Association of asymptomatic bacterial vaginosis with persistence of female genital human papillomavirus infection. Eur J Clin Microbiol Infect Dis 2017; 36:2215–2219.
Łaniewski P, Barnes D, Goulder A, et al. Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women. Sci Rep 2018; 8:7593.
Usyk M, Zolnik CP, Castle PE, et al. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog 2020; 16:e1008376.
Mitra A, MacIntyre DA, Ntritsos G, et al. The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat Commun 2020; 11:1999.
Oh HY, Kim BS, Seo SS, et al. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea. Clin Microbiol Infect 2015; 21:674.e1–674.e9.
Borgdorff H, Tsivtsivadze E, Verhelst R, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J 2014; 8:1781–1793.
Zhang C, Liu Y, Gao W, et al. The direct and indirect association of cervical microbiota with the risk of cervical intraepithelial neoplasia. Cancer Med 2018; 7:2172–2179.
Adebamowo SN, Ma B, Zella D, et al. Mycoplasma hominis and Mycoplasma genitalium in the vaginal microbiota and persistent high-risk human papillomavirus infection. Front Public Health 2017; 5:140.
Balkus JE, Srinivasan S, Anzala O, et al. Impact of periodic presumptive treatment for bacterial vaginosis on the vaginal microbiome among women participating in the preventing vaginal infections trial. J Infect Dis 2017; 215:723–731.
McClelland RS, Balkus JE, Lee J, et al. Randomized trial of periodic presumptive treatment with high-dose intravaginal metronidazole and miconazole to prevent vaginal infections in HIV-negative women. J Infect Dis 2015; 211:1875–1882.
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.
Srinivasan S, Hoffman NG, Morgan MT, et al. Bacterial communities in women with bacterial vaginosis: High resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One 2012; 7:e37818.
Mandal S, Van Treuren W, White RA, et al. Analysis of composition of microbiomes: A novel method for studying microbial composition. Microb Ecol Health Dis 2015; 26:27663.
Motevaseli E, Azam R, Akrami SM, et al. The effect of Lactobacillus crispatus and Lactobacillus rhamnosus : Culture supernatants on expression of autophagy genes and HPV E6 and E7 oncogenes in the HeLa cell line. Cell J 2016; 17:601–607.
Nouri Z, Karami F, Neyazi N, et al. Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on HeLa and HT-29 cell lines. Cell J 2016; 18:127–134.
Wang K-D, Xu D-J, Wang B-Y, et al. Inhibitory effect of vaginal lactobacillus supernatants on cervical cancer cells. Probiotics Antimicrob Proteins 2018; 10:236–242.
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.
Vaneechoutte M, Guschin A, Van Simaey L, et al. Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii sp. nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella . Int J Syst Evol Microbiol 2019; 69:679–687.