Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis

Nele Brusselaers; Sadeep Shrestha; Janneke van de Wijgert; Hans Verstraelen

doi:10.1016/j.ajog.2018.12.011

Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis

Am J Obstet Gynecol. 2019 Jul;221(1):9-18.e8. doi: 10.1016/j.ajog.2018.12.011. Epub 2018 Dec 12.

Authors

Nele Brusselaers¹, Sadeep Shrestha², Janneke van de Wijgert³, Hans Verstraelen⁴

Affiliations

¹ Centre for Translational Microbiome Research, Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; Science for Life Laboratory, Stockholm, Sweden; Department of Oto-Rhino-Laryngology, Ghent University, Ghent, Belgium. Electronic address: Nele.Brusselaers@ki.se.
² Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama.
³ Department of Clinical Infection, Microbiology, and Immunology, University of Liverpool, Liverpool, United Kingdom; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴ Department of Obstetrics and Gynecology, Ghent University, Ghent, Belgium.

PMID: 30550767
DOI: 10.1016/j.ajog.2018.12.011

Abstract

Objective: The vaginal microbiota proposedly influence the association between human papillomavirus and cervical cancer. Our aim was to assess whether vaginal dysbiosis affects human papilloma virus acquisition, persistence, and progression to related cervical premalignancy.

Data soruces: MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science (inception until June 2018) were used for this study. The study protocol was registered at PROSPERO (CRD42016035620).

Study eligibility criteria: This systematic review included all observational studies reporting on incident human papilloma virus, persistent human papilloma virus, and/or related cervical disease in women with or without vaginal dysbiosis prior to outcome assessment.

Study appraisal and synthesis methods: We used random-effects models for meta-analyses and report pooled relative risks with 95% confidence intervals. The risk for incident and/or persistent human papilloma virus or related cervical disease based on longitudinal results was determined.

Results: Of 1645 unique articles, 15 mainly prospective cohort studies were included, published between 2003 and 2017, including a total of 101,049 women. Vaginal dysbiosis was associated with an increased risk of incident human papilloma virus (overall relative risk, 1.33, 1.18-1.50, I² = 0%; among young women relative risk, 1.43, 1.10-1.85, I² = 0%), human papilloma virus persistence (overall relative risk, 1.14, 1.01-1.28, I² = 44.2%; for oncogenic types relative risk, 1.18, 1.01-1.38, I² = 0%), and high-grade lesions and cancer (relative risk, 2.01, 1.40-3.01, I² = 0%), but women with lesions/cancer were compared with those without, regardless of their oncogenic human papilloma virus status. Overall, comparable results were found in the molecular vaginal microbiota studies.

Conclusion: This study supports a causal link between vaginal dysbiosis and cervical cancer along the oncogenic human papillomavirus acquisition, persistence, and cervicovaginal dysplasia development pathway.

Keywords: HPV; bacterial vaginosis; human papillomavirus; microbiome; vaginal dysbiosis.

Publication types

Systematic Review

MeSH terms

Disease Progression
Dysbiosis / epidemiology*
Female
Humans
Microbiota
Papillomavirus Infections / epidemiology*
Precancerous Conditions / epidemiology
Uterine Cervical Dysplasia / epidemiology*
Uterine Cervical Neoplasms / epidemiology*
Vagina / microbiology*