Reviewer ’s report  
 
Title: The influence of probiotics on genital high -risk human papilloma virus clearance, 
associated lesions and quality of cervical smear: A randomized placebo -controlled trial  
 
Version: 0 Date: 13 Mar 2019  
 
Reviewer: Alessandra Pierangeli  
 
Reviewer's report:  
The study "The influence of probiotics on genital high -risk human papilloma virus clearance and  
quality of cervical smear" gives a contribution on the important issue of the probiotics 
effectiveness in reducing vaginal colonization of HPV. In a randomized, double -blinded, 
placebo -controlled trial  121 women were enrolled (62 in the study group and 59 in the control 
group). The study group received the probiotic bacteria Lactobacillus rhamnosus GR -1 and 
Lactobacillus reuteri RC -14 and all wome n  were tested every 3 months with cytology and HR -
HPV until a negative result was obtained. There was no significant difference in HPV clearance 
whereas HPV load estimated with the HC2 test was found as an independent factor predicting 
HPV clearance in bo th groups.  
 The interest is related to the finding of significant decrease in mildly abnormal cytology, in the 
study group  
(13 to 4) compared to the control group (9 to 6) (p=0.017). The authors also consider relevant the 
differences in the unsatisfactory  reports between the two groups.  
This study is well written but has some weakness in the study design. First of all, the sample size 
was small and second, it is not clear whether enrolled patients had a clinical diagnosis of 
bacterial vaginosis (BV), that  as the authors stated, may have a strong influence on the clearance 
of HPV -associated lesions.  
 
Moreover, it should be revised in several points, as detailed below.  
Title: "The influence of probiotics on genital high -risk human papilloma virus clearance " is not 
entirely correct: it should be modified in high -risk human papilloma virus -associated lesions.  
 
Methods  
A definition of unsatisfactory cervical smear should be given.  
 
Discussion  
The sentence "BV was independently associated with HPV infection" i s not referenced and it is 
not clear whether it refers to this study group.  
Findings from other recent papers on the use of probiotic strains in HPV -positive patients should 
be discussed  
Are the methods appropriate and well describ ed? 
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.  
 
Yes 
 
Are you able to assess any statistics in the 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  
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3. Do you hold or are you currently  applying for any patents relating to the content of the 
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5. Do you have any other fi nancial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
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below. If your reply is yes to any, please give detai ls below.  
 
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