Reviewer ’s report  
 
Title: The disease stage -associated imbalance of Th1/Th2 and Th17/Treg in uterine cervical  
cancer patients and their recovery with the reduction of tumor burden  
 
Version: 1 Date: 30 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
Yes - there is a clear objective  
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
No - there are minor issues  
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
Yes - experiments and analyses were performed appropriately  
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
Yes - appropriate statistical analyses have been used in the study  
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
Yes - the author's interpretation is reasonable  
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
Maybe - with maj or revisions  
 
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS:  
Overall, the study is well -performed however there are some issues authors need to address to 
improve the manuscript.  
 
REQUESTED REVISIONS:  
Issues authors must address are the following: Authors s tate in the background section that 
studies on this topic in cervical cancer are rare. This is not. The paragraph in regard to reference 
15 is incorrectly taken. The reason why these women have not adequate cervical cancer 
screening is not that they have f ewer risks. In fact, their immunosuppression increased the risk. 
Less screening derives from other reasons. Controls must be more clearly described. They were 
taken to cervical smear? they were HPV tested? this will clarify if they were healthy in the 
regard pertaining to this work. Most importantly, the discussion is poorly done. It essentially 
repeats the findings of the results. Reference 21 in the discussion has nothing to do with this 
work. In fact, the only reference that authors take to contrast thei r results with others is reference 
25. There are more than 10 articles addressing the topic of this study. FINALLY and not least 
important. Authors DO NOT REFERENCE their previous work. To avoid readers think this is a 
duplicate work, AUTHORS should disclo se if there are any duplicated results from that. This is 
the reference:                                            Int J Clin Exp Pathol. 2019; 12(9): 3604 -3612.  
Published online 2019 Sep 1.  
PMCID: PMC6949808  
PMID: 31934210  
Imbalance of Th1/Th2 and Th17/T reg during the development of uterine cervical cancer  
Wei Lin,1 Zhaoyuan Niu,1 Hualing Zhang,1 Yan Kong,1 Zhen Wang,1 Xingsheng Yang,2 Fang 
Yuan1  
Author information Article notes Copyright and License information Disclaimer  
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Abstract  
Uterine cervical cancer (UCC) causes more than one quarter of a million deaths per year in many 
developing countries. Nearly all cases of cervical cancer result from infection with the human 
papillomavirus. After high -risk HPV infection, most HPV infection s are cleared naturally as a 
result of humoral and cell -mediated immune responses. Only a limited number of patients' 
cervical lesions progress through CIN to cervical cancer, from persistent oncogenic human 
papillomavirus (HPV) infection. This indicated t hat immunoregulation may play a central role in 
the HPV -induced carcinogenesis. However, the natural history of clearance of a cervical HPV 
infection or its progression to a UCC needs clarification. We examined the related immune cells 
(Th1, Th2, Th17 and Treg cells) and related immune factors (INF -γ, IL -4, IL -10, IL -17, IL -23, 
TGF -βI) of UCC patients, CIN patients, HPV infected patients, and healthy controls. Compared 
with healthy controls, patients with UCC or CIN had a lower proportion of Th1 cells, and a 
higher proportion of Th2, Th17, and Treg cells. IL -4, IL -10, IL -17, IL -23 and TGF -βI 
concentrations in serum were found to be increased from patients with UCC or CIN, while INF -γ 
concentration in serum with UCC or CIN decreased. Our findings suggested th at there were 
attractive imbalances of Th1/Th2 and Th17/Treg cells in UCC and CIN patients. HPV persistent 
infection induced an immunologic dissonance, and the degree of imbalance is aggravated with 
the progression of the disease.  
 
Keywords: Uterine cervic al cancer, cervical intraepithelial neoplasia, T helper 17, T helper 1, T 
helper 2, Treg  
 
ADDITIONAL REQUESTS/SUGGESTIONS:  
None  
 
 
 
 
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.  
 
No 
 
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 addition al 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 recei ved 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.  
 
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agreed to publication of their comments online under a Creative Commons Attribution License  
attributed to Research Square and was paid a small honorarium  for completing the review within 
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