Reviewer ’s report  
 
Title: Cervical microbiota in women with cervical intra -epithelial neoplasia, prior to and after 
local excisional treatment, a Norwegian cohort study.  
 
Version: 0 Date: 17 Sep 2018  
 
Reviewer: Yi-Chang Su  
 
Reviewer's report:  
 
This prosp ective observational study aimed to compare the cervical microbiota in women with 
CIN before and after LEEP and to assess whether cone depth and/or HPV persistence affects 
bacteria composition post -treatment. This research topic is interesting, and Zhang e t al. had 
reported the same topic with the opposite result this March. (Zhang H, Lu J, Lu Y, Cai Q, Liu H, 
Xu C. Cervical microbiome is altered in cervical intraepithelial neoplasia after loop 
electrosurgical excision procedure in china. Sci Rep. 2018 Mar 21;8(1):4923. doi: 
10.1038/s41598 -018-23389 -0)  
https://www.nature.com/articles/s41598 -018-23389 -0  
Though the sample size of this study is larger than Zhang's, there are several obvious flaws in the 
study design, which makes the results not solid and conv incing. There are also some inadequate 
assumptions and inferences in the manuscript. The authors are suggested to revise and add more 
details about the participators, and analyze the effects of the related factors that may influence 
the cervical microbiota . 
1. Since the cervical microbiota is the most important variables observed in this study, and the 
microbiota variety is closed related to the menopausal status, use of hormone replacement 
therapy, the time of menstruation, menstrual hygiene practices, use  of vaginal douching, 
sexual behaviors, use of hormonal or barrier contraceptive products, numbers of sexual 
partners, history of recent sexual activity and antibiotics/probiotics (oral or topical) for other 
diseases; the authors should record and analyze the effects of these related factors of each 
participants instead stating these may impact the results as the study limitations.  
 
2. The authors should mention the time of the sample collection. If the participants had 
menstruation or sexual activity in the previous days which may influence the cervical 
microbiota.  
 
3. The participants in LEEP group were younger and more of them were single, whether their 
sexual behavior patterns and contraceptive use have changed after the diagnosis of CIN and 
receiving LEEP w ere not followed and recorded. Without the above information, the results 
are not convincing.  
 
4. The discussion about the risk of preterm delivery (PTD) is not reasonable. PTD may result 
from other factors and pregnant women were excluded in the follow -up analysis. Meta -
analyses published a few years ago in the Lancet and the BMJ showed an increased risk of 
adverse obstetric outcomes after treatment for CIN. The cause remains unclear, and potential 
mechanisms include anatomical changes, cicatrisation of the  cervix, immunological factors, 
and alterations of the cervicovaginal flora. As the author said in the article: "The results were 
not significant possibly due to small sample size."(P.15, line12) In addition, the study 
couldn't control the interference fac tors, so the authors couldn't determine the reason why the 
study result was different from the previous research results, and couldn't explained the 
relation between LEEP therapy, microbial colonization and preterm delivery.  
 
Other minor issues:  
1. The Tabl e 1 should be moved to the "Results."  
 
2. In Table 4: the authors should explain in more detail about why authors group the women 
with the bacterial findings "Pos -pos, Neg -neg, Neg ->pos" into one category.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in th e manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
  
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain  or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary  from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests' below.  
 
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