Accepted Manuscript

Bacterial Vaginosis and the risk of human papillomavirus and cervical cancer

Makella Coudray, Sandra Kiplagat

PII: S0002-9378(19)30674-X
DOI: https://doi.org/10.1016/j.ajog.2019.05.016
Reference: YMOB 12684

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 21 March 2019

Accepted Date: 14 May 2019

Please cite this article as: Coudray M, Kiplagat S, Bacterial Vaginosis and the risk of human
papillomavirus and cervical cancer, American Journal of Obstetrics and Gynecology (2019), doi: https://
doi.org/10.1016/j.ajog.2019.05.016.

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 ACCEPTED MANUSCRIPT

Bacterial Vaginosis and the risk of human papillomavirus and cervical cancer

Makella Coudray1, Sandra Kiplagat1

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Department of Epidemiology, Robert Stempel College of Public Health and Social

Work, Florida International University

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Corresponding Author

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Makella Coudray, MPH, CPH

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Department of Epidemiology, Robert Stempel College of Public Health and Social Work,

Florida International University

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Miami, Florida
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33199

mcoud001@fiu.edu
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Funding
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Makella Coudray was supported by the National Institutes of Health grant (R15AI28714-
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01). The content is solely the responsibility of the authors and does not necessarily

represent the official views of the National Institutes of Health or Florida International
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University.
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Conflict of Interest
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The authors report no conflict of interest.

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To the Editors:

In response to the article titled “Vaginal dysbiosis and the risk of human papillomavirus and cervical

cancer: systematic review and meta-analysis” we the authors believe that the findings of Brusselaers et al.

could potentially support the theory that there is a causal link between vaginal dysbiosis and cervical

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cancer.1 However, before this theory can be fully supported, issues of ambiguity identified in this systematic

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review should be addressed. Brusselaers et al aimed to assess the association between vaginal dysbiosis

and cervical cancer.1 Concerns arise with respect to the definition of vaginal dysbiosis that was used and

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the study selection criteria.

Firstly, vaginal dysbiosis was defined as a deviation from a Lactobacillus-dominant microbiota.

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However, a definitive cut off point for Lactobacillus dominance was never identified and this may vary from
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study to study. Further confusion occurs since the definition used by Brusselaers et al uses microscopy-

based assessment of Lactobacillus-dominance but the authors included studies that used Amsel’s criteria.
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Amsel’s criteria does not directly assess Lactobacillus-dominance, rather it assesses the presence or
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absence of clue cells via microscopy.2 Additionally, the presence of clue cells is not required for diagnosis
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of vaginal dysbiosis. Three of the four Amsel’s criteria are required to be diagnosed with vaginal dysbiosis

of which presence of clue cells is only one.2 This may have resulted in an overestimation of results due to
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misclassification. It should also be noted that it is possible to have a Lactobacillus-dominant vaginal

microbiota and be classified as unhealthy or exhibit characteristics similar to that of a vaginal microbiota
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that has deviated from Lactobacillus-dominance.3

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Secondly, we are concerned that Brusselaers et al acknowledge vaginal dysbiosis is also

commonly referred to as bacterial vaginosis, however, this term was not included in the search strategy.

Furthermore, though the authors used MESH and Emtree terms, CINAHL headings were not included in

the search strategy for the CINAHL database. Further clarity is also needed with respect to the inclusion of

grey literature. Conference abstracts were cross checked for relevant full text papers, however, the time
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frame and conferences that were searched were not included. We acknowledge the efforts of Brusselaers

et al to assess bias, however, a customized tool was used for assessment of risk of bias and the validity of

the tool could not be verified. It was not clearly expressed if this tool was validated or piloted prior to its use.

Additionally, the authors failed to assess publication bias. Funnel plots could have been used to graphically

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assess publication bias. Brusselaers et al amply highlight the need for further investigation into the

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association between vaginal dysbiosis and the risk of human papillomavirus and cervical cancer.

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References

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1. 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
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Gynecol. 2018.
2. Onderdonk AB, Delaney ML, Fichorova RN. The Human Microbiome during Bacterial Vaginosis.
Clin Microbiol Rev. 2016;29(2):223-238.
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3. Petrova MI, Reid G, Vaneechoutte M, Lebeer S. Lactobacillus iners: Friend or Foe? Trends
Microbiol. 2017;25(3):182-191.
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