Reviewer ’s repo rt 
 
Title: HPV Vaccine in the Treatment of Usual type Vul val and Vaginal Intraepithelial 
Neoplasia: A Systematic Review  
 
Version: 0 Date: 24 Aug 2018  
 
Reviewer: Annarosa Del Mistro  
 
Reviewer's report:  
 
The manuscript by Brayan and collaborators presents a systematic review on the use of HPV 
vaccines in the treatment of preneoplastic lesions of the vulva and vagina. The topic is of interest 
and the review is new in this field, but the results are not adeq uately presented.  
 
 
 
Major observations:  
 
- HPV vaccines: the literature search included experimental therapeutic vaccines as well as 
commercially available prophylactic vaccines used with treatment intention, but the 7 
papers meeting the inclusion criteria a ll deal with therapeutic vaccines; this should be 
made clear in the paper (starting with the title) and the prophylactic vaccines should not 
be referred to in the discussion  
 
 
- patients' characteristics: a total of 129 women were included in the studies; 12 6 had VIN 
and only 3 had VAIN (and this should be stated in the results and in the table); time of 
lesions' duration and previous therapies should also be reported  
 
 
- aim of the review: who is the target audience?  
 
 
- background: an overview on existing ther apeutic vaccines, their characteristics and their 
use and efficacy on cervical lesions should be added; a useful reference to include could 
be Vici et al. Exp Rev Vaccines 2016;15:1327 -1336  
 
 
- data on the therapeutic vaccines used in the 7 included studies should be added  
 
 
- immune response: these results should be summarized and the main findings discussed in 
reference to the data on cervical lesions  
 
- lenght of follow -up: it ranged between 1 and 12 months, and reporting how long the 
efficacy was eventually recorded would be useful  
 
 
- combined treatment: the HPV therapeutic vaccine was administered with Imiquimod in 
one of the studies (Daayana, 2010); is there any evidence of efficacy of combination 
treatments in trials of women with cervical lesions?  
 
 
 
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 autho rs. 
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the edito rs. 
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following quest ions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 com peting 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.  
  
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