The vaginal microbiota and its association with human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections: a systematic review and meta-analysis

Abstract

Background: The vaginal microbiota may modulate susceptibility to human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections. Persistent infection with a carcinogenic HPV is a prerequisite for cervical cancer, and C. trachomatis, N. gonorrheae and M. genitalium genital infections are all associated with pelvic inflammatory disease and subsequent infertility issues.

Objectives: To evaluate the association between these infections and the vaginal microbiota.

Data sources: The search was conducted on Medline and the Web of Science for articles published between 2000 and 2016.

Study eligibility criteria: Inclusion criteria included a measure of association for vaginal microbiota and one of the considered STIs, female population, cohort, cross-sectional and interventional designs, and the use of PCR methods for pathogen detection.

Methods: The vaginal microbiota was dichotomized into high-Lactobacillus vaginal microbiota (HL-VMB) and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or gene sequencing. A random effects model assuming heterogeneity among the studies was used for each STI considered.

Results: The search yielded 1054 articles, of which 39 met the inclusion criteria. Measures of association with LL-VMB ranged from 0.6 (95% CI 0.3-1.2) to 2.8 (95% CI 0.3-28.0), 0.7 (95% CI 0.4-1.2) to 5.2 (95% CI 1.9-14.8), 0.8 (95% CI 0.5-1.4) to 3.8 (95% CI 0.4-36.2) and 0.4 (95% CI 0.1-1.5) to 6.1 (95% CI 2.0-18.5) for HPV, C. trachomatis, N. gonorrhoeae and M. genitalium infections, respectively.

Conclusions: Although no clear trend for N. gonorrhoeae and M. genitalium infections could be detected, our results support a protective role of HL-VMB for HPV and C. trachomatis. Overall, these findings advocate for the use of high-resolution characterization methods for the vaginal microbiota and the need for longitudinal studies to lay the foundation for its integration in prevention and treatment strategies.

Keywords: Chlamydia trachomatis; Human papillomavirus; Meta-analysis; Mycoplasma genitalium; Neisseria gonorrhoeae; Sexually transmitted infection; Vaginal microbiota.

Figure 1.

Flow chart of selection process for article identification and inclusion. BV: Bacterial vaginosis.

Figure 2.

Forest plots of association between vaginal microbiota and A) Human Papillomavirus (HPV), B) Chlamydia trachomatis (Ct), C) Neisseria gonorrhea (Ng), D) Mycoplasma genitalium (Mg). OR: Odds-ratio; RR: Relative Risk; IRR: Incident Rate Ratio; HR: Hazard Ratio; ES: effect size; CI: confidence Interval. Adjusted measures are indicated by the a-suffix in front of the measure of association. ORs calculated from raw data are indicated by the c-suffix.

Figure 3.

Subgroup analysis of association between vaginal microbiota and HPV, by A) age group, B) study site, C) OR versus other effect size measures, D) adjusted versus non-adjusted effect sizes, E) vaginal microbiota assessed before infection versus at the same time as infection, F) diagnosis method.

Figure 4.

Subgroup analysis of association between vaginal microbiota and C. trachomatis, by A) age group, B) study site, C) OR versus other effect size measures, D) adjusted versus non-adjusted effect sizes, E) vaginal microbiota assessed before, after and at the same time as infection, F) diagnosis method.