Reviewer’s report  
 
Title: Feasibility of endometrial sampling by vaginal tampons in women with Lynch syndrome  
 
Version: 0 Date: 16 Sep 2019  
 
Reviewer: Emma Crosbie  
 
Reviewer's report:  
 
Thank you for asking me to review this manuscript, which I found  very interesting. This is a 
topical area - non-invasive endometrial cancer diagnosis - but I am not aware of any previous 
studies attempting this in women with Lynch syndrome, who are at increased lifetime risk of 
endometrial cancer.  
 
In general the manus cript is well written but the references are out of date. Please cite newer 
studies including: (1) Dominguez -Valentin M et al Genet Med. 2019 Jul 24. doi: 
10.1038/s41436 -019-0596 -9; (2) Ryan NAJ et al JAMA Oncol. 2017 Dec 1;3(12):1702 -1706. 
doi: 10.1001/ja maoncol.2017.0619, which give a more contemporary understanding of the risks 
of gynaecological cancers in women with Lynch syndrome.  
 
I disagree with the statement: "Annual surveillance of women with LS to detect endometrial 
abnormalities in a premalignant  or early malignant stage is effective." A recent international 
consensus meeting concluded that there was insufficient evidence to recommend gynaecological 
surveillance in women with Lynch syndrome, please see: Crosbie EJ et al Genet Med. 2019 Mar 
28. doi : 10.1038/s41436 -019-0489 -y. This group of international experts came to this conclusion 
because there is no evidence that detecting atypical hyperplasia or endometrial cancer through 
surveillance saves lives. Indeed, recent evidence suggests that colonosc opic surveillance in 
Lynch syndrome may not be as effective as it was once thought: Seppälä TT. Hered Cancer Clin 
Pract. 2019 Feb 28;17:8. doi: 10.1186/s13053 -019-0106 -8. I feel quite strongly that this part of 
the manuscript should be re -written to reflec t this uncertainty, particularly since this manuscript 
may be seen as endorsing practice that may not be helpful to women and may in fact be harmful 
(through anxiety, false reassurance, costs, harms of surveillance, over diagnosis and so on). 
Nonetheless, there is uncertainty about gynaecological surveillance and its role in Lynch 
syndrome so studies in this area are not only welcome but important. I just think it is 
disingenuous to write the introduction as though surveillance has a proven role.  
 
 
I have th e following comments/requests for clarity:  
 
(1) Why didn't the authors look for genomic abnormalities as biomarkers for disease? One would 
think this approach would be more sensitive than cytology.  
 
(2) I would like to know about the 7 women who declined. C an the authors describe their 
characteristics in the table alongside those who participated? The reason why this is important is 
that our work suggests that tampons for endometrial sampling in endometrial cancer patients are 
less acceptable to older women.  This may mean that tampons are actually a relatively good 
choice for endometrial surveillance in Lynch women, who are younger than sporadic 
endometrial cancer patients. Can the authors clarify?  
 
(3) I understand why the authors compared VAS scores after ta mpon removal and endometrial 
biopsy - but it is logical that they were different. I think it is important to note that many women 
are used to wearing vaginal tampons during menstruation and therefore this is unlikely to be a 
painful thing, or they wouldn't  choose to do it.  
 
(4) How did the authors decide on their sample size? Can they provide a sentence or two about 
their power calculation? Perhaps the study would have had different findings if they had sampled 
more women - can they comment on how frequently  they pick up endometrial abnormalities in 
their clinic? This could have been factored into a power calculation. It is actually quite 
uncommon to detect endometrial abnormalities in Lynch women undergoing surveillance, and so 
a larger study size is needed if trialing a new method of cancer detection.  
 
This paper shows that tampons aren't painful but endometrial biopsies are (this is known) and 
that tampons collect vaginal cells (this is assumed but not relevant to this study). The authors 
have not shown th at they can detect endometrial abnormalities or collect endometrial cells from 
asymptomatic women. However, I really like the idea of trying to advance surveillance 
procedures towards less invasive practice and this study is trying something innovative and  
important.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
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 supporte d by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
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 spe cify 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 reimburse ments, 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 organi zation 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 am interested in non -invasive sampling for endometrial cancer detection and Lynch syndrome -
associated endometrial cancer.  
 
I agree to the open peer review policy of the journal. I understand that my name will  be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available unde r an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be p ublished.  
 
I agree to the open peer review policy of the journal