Title: Association between bacterial vaginosis with human papillomavirus in the United States
(NHANES 2003–2004)
Version: 3 Date: 28 Oct 2023
Reviewer:  António MacHado
Reviewer's report:
Reviewer report of the Manuscript ID b2e5c489-eb60-43c3-b56a-c5fff72dceac
Congratulations on the present study! However, the manuscript is a draft proposal that requires
major revisions.
General comments
The present study is more suitable for a brief research report or short communication instead of
an original full-length article. However, this decision should be made by the journal editor.
All manuscript sections showed several typos and microbiological errors. Please see my minor
comments below.
Some concerns were raised in the Methods section. Please thoroughly address them to avoid
misunderstanding of the Readers.
The Results and Discussion sections need major improvements and the authors must
acknowledge the several shortcomings of the study at the end of the Discussion section (the
authors only mentioned one). Please carefully see my minor comments below.
Minor comments
Abstract
Please rephrase the conclusion by stating the variables/adjustments that indicated this positive
association to avoid a general statement. Also, I recommended adding some numerical data
values obtained from the logistic regression analysis and subgroup analysis. No data is shown
to the Readers in the summary/abstract.
Introduction
Please state the full names of BV and HPV in the first sentence of the Introduction section and
delete the full names of HPV added in the fourth line and “Bacterial vaginosis (BV)” in line 28
of the Introduction section.
Line 24- Please add the term high-risk human papillomavirus (HR-HPV) in “Continuous
infection with human papillomavirus (HR-HPV)”.
Lines 30-31- Please put the bacteria names in italic form, in this case, “Gardnerella vaginalis
(GV)” and Trichomonas vaginalis (TV) at line 33. Please check the remaining text of the
manuscript, I will assume that all text of the manuscript will be checked to avoid repeating all
locations of the bacteria names written in the manuscript.
Line 34- Please check the citations of the references. The references are not correctly cited. Also,
please replace “vaginal microbiology” with “vaginal microbiota”.
Line 40- Please replace American women with U.S. women.
Methods
Lines 66-67- “(1: non-Hispanic white, 2: non-Hispanic black, 3: Mexican American, and 4:
other races)” The authors stated “3: Mexican American” and previously indicated non-Hispanic
white or black. Are you sure that the category of Mexican American differentiates Mexican
women from Hispanic women? I am not sure, but I would guess that the third category should
be Hispanic women due to the diversity of ethnic groups in the US engaging more than Mexican
women, right?
Lines 71-72- The health-related variable “alcohol (whether drank at least 12 alcoholic beverages
in 1 year)” is misleading the Readers. At least 12 beverages in 1 year constitute 1 beverage per
month, which should not be classified as frequent alcohol consumers, and grouping these persons
with heavy drinkers is not correct for an epidemiologic evaluation of alcohol consumption.
Please re-evaluate this health-related variable on the group set or acknowledge this shortcoming
of the present study in the Discussion section state for the non-familiar Readers. This is not a
recommendation.
Statistical analysis at lines 74-82- In multivariable logistic regression analyses, it is important to
evaluate the false discovery rate (FDR) for conducting multiple comparisons such as Benjamini–
Hochberg (BH) adjustment (check DOI: 10.1038/s41598-020-74655-z). Please clarify the
Readers. Also, please properly cite R software and include the used R packages (check DOI:
10.1371/journal.pone.0263522) of the present study.
Results
Table 1 and Table 2- Please rectify the typo errors, some examples are the following: “Negtive”,
“Postive”, “Non-adjusted moedel”, “presected table 1”, and “withBV”.
Lines 90-91- “Figure 1 shows HPV infection rates among women with and without BV.” I
recommend Figure 1 to illustrate statistical comparisons between the two group sets.
Line 97- Rectify the several type errors such as “table 2” in the Results section.
Discussion
Lines 107-108- “The maintenance of a balanced microenvironment in the vagina is crucial
for preventing infections of the female genital tract and minimizing the risk of cervical
lesions (Mitra et al., 2016).”  Please replace “microenvironment in the vagina” with “vaginal
microbiota” and state the importance of lactobacilli protection, as described in other studies such
as DOI: 10.3389/fcimb.2022.863208, DOI: 10.3390/antibiotics10080978, and DOI: 10.1038/
s41598-020-74655-z.
Lines 123 and 124- Please replace “both intrinsic and adaptive immunity” with “both innate and
adaptive immunity” and “intrinsic immunity” with “primary or innate immunity”.
Lines 124-128- “The predominant organism in healthy women of childbearing age is
Lactobacillus, regardless of ethnic differences in vaginal flora (Ravel et al., 2011; France et
al., 2020). However, BV may alter the cervicovaginal microenvironment from the dominant
lactobacilli to a poly-microbiome composed of strictly facultative anaerobic bacteria (Coleman
and Gaydos, 2018).” Please rectify:
1. Lactobacillus must be in italic form;
2. The predominant genus/species and not organism;
3. Vaginal microbiota or microbiome instead of vaginal flora;
4. Dysbiosis instead of poly-microbiome.
Lines 130-131- Please put all bacteria names in the italic form. There is no microorganism so-
called “Apococcus vaginalis” in BV infections, do you mean Mobiluncus mulieris or Atopobium
vaginae (now reclassify as Fannyhessea vaginae: https://www.ncbi.nlm.nih.gov/Taxonomy/
Browser/wwwtax.cgi?mode=Info&id=82135)?
Also, Lactobacillus curvatus is not a common BV-related pathogen: https://
www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?
mode=Info&id=28038&lvl=3&lin=f&keep=1&srchmode=1&unlock, so I suggested to replace
it with a more frequently identified secondary BV-related infections.
Line 133- Another type of error: “BRISELDEN et al. (Briselden et al., 1992)”.
Line 154- Another type of error: “In addition, We also”.
Lines 154-158- “The weakness of this study is that it was a cross-sectional study and data on
BV and HPV infection were collected simultaneously rather than over time. Thus, the sequence
of HPV and BV infection is not known, and whether BV increases the risk of HPV infection
or HPV increases susceptibility to BV we cannot answer# this conclusion requires further
prospective studies of intervention trials.” There are several shortcomings of the study that must
be acknowledged by the authors for publication endorsement.
Lines 165-167- Please state the approval numbers of the present study:
“1.Ethics approval and consent to participate
All participants provided written informed consent, and the study was approved by the NCHS
Research Ethics Review Board.”
Lines 181-183- “8.Contributions
JQandLS wrote the main manuscript text and JZ:date analysis.JQ#LS#JZandCD reviewed the
manuscript”