Reviewer ’s report  
 
Title:  Characteristics of cervical disease among symptomatic women with histopathological 
sample at Hawassa University referral hospital, Southern Ethiopia  
 
Version: 2 Date: 18 Aug 2016 
 
Reviewer:  Alejandra  Castanon  
 
Reviewer’s report:  
 
Dear Editor,  
 
I would commend the authors on the changes they have made to the methods, results and tables 
of the study. The paper is much better and has a better focus. However this has not translated into 
their discussion.  
 
I have found many factual inaccuracies as well as poorly researched statements. The discussion 
is not focused and it is difficult to see what the main points of the paper are. Below are my 
detailed comments.  
 
 
Title:  Authors only show one graph with number of samples by diagnosis and year of sample so 
I'm not sure you can claim the aim is to show the trends, whereas you do give a good description 
of the disease among those samples. It seems to me that the aim and titl e should be something 
similar to "characteristics of cervical disease among symptomatic women with a 
histopathological sample at Hawassa University referral hospital."  
 
 
Abstract: needs some English improvements  
 
Ensure that the aim in line 24 -25 is the same as the aim in line 105 -106 of the background.  
 
Could the authors clarify line 104 of the background: do they mean that no histopathological 
report is issued? How do the clinicians know the diagnosis following a  biopsy? Do they mean 
that histopathological reports are not archived and therefore they cannot be reviewed therefore 
the authors had to re -read all of the samples for this study?  
 
So as not to say almost increasing throughout study period (line 40 -41) a ch i2 test for trend could 
be carried out.  
 
 
Results: line 141, How do we know that all women with symptoms had a histological sample 
taken? Surely this should read "about 39% of women with a sample were age….."  
 
One decimal place for all numbers in text and tab les is sufficient.  
Discussion:  
 
Strengths and limitations should mention how robust the study is to ensure that all women with 
symptoms had a biopsy - surely the authors do not know this which is why the study is purely 
reporting on the disease among the s amples received at the lab. This point is key when 
comparing this to other published studies. I have made more in depth comments about this 
below.  
 
Observing the highest incidence of cervical cancer in post -menopausal women is not surprising 
the natural hi story of the disease suggests that this age group would be the most affected. It is 
only screening (or any form of early diagnosis) that changes the natural history resulting in 
diagnosis at earlier ages (when the cancer is still largely asymptomatic).  
 
The discussion needs to make clear that there are two different issues  
 
1) Half (49%) of cervical disease is cancer whereas 10% is precancerous disease. This 
reflects the very limited cervical screening in the region. Precancerous lesions are solely 
diagnosed through screening or incidental findings while investigating symptoms (as is the case 
in this study). Therefore the sentence in line 182 -183 is not accurate.  
 
2) Prognosis of cervical cancer is linked to differentiation so if a large proportion of cancers 
are poorly differentiated they will have worst prognosis. Perhaps you should show differentiation 
for adenocarcinoma?  
 
Are there any papers that show that where organised screening programmes exist the vast 
proportions of cervical disease in symptomatic wome n is not due to cervical cancer or 
precancerous lesions?  
 
Differentiation does affect prognosis of the cancer with poorly differentiated cancers having 
worse survival (http://onlinelibrary.wiley.com/doi/10.1046/j.1525 -
1438.1991.01040173.x/abstract) > howev er according to IARC between 50 -60% of the SCC 
cancers are moderately differentiated (this study found 46%) 
http://screening.iarc.fr/colpochap.php?chap=3. The rest of the SCC are evenly divided between 
poorly and well differentiated according to IARC, the results of this study are not dissimilar. 
However the authors seem to suggest in the discussion that the differentiation of somehow linked 
to the symptoms (line 210 in discussion) this needs a reference or further clarification. 
Symptoms are linked to stag e and stage does not appear to be linked to differentiation. If I am 
wrong then a reference needs to be added linking differentiation to stage.  
 
How does the age distribution of histological differentiation vary from other studies? Would it be 
of interest to present the differentiation for adenocarcinoma?  
 
Lines 187 -191: I do not see the value of mentioning the pap test in the discussion as this study is 
not assessing sensitivity or specificity of any test.  
 
Line 195: I was not able to access reference 20, h owever one wonders whether a difference in 
methodologies could be responsible for the difference in the prevalence of cervical cancer among 
symptomatic women. In the Addis Ababa study samples were taken from women with post -
menopausal bleeding and we know that endometrial cancer would be the main cause of this 
rather than cervical cancer.  
 
Paragraph starting line 198: Authors have confused arguments. The Malaysian study found SCC 
to be the most common cervical cancer histology. However they found a higher p roportion of 
CIN (42%) among the population. Again I can't access the full article but presumably the study 
population in the Malaysian study is not comparable to this one (i.e. levels of screening and the 
proportion of samples taken in symptomatic women).  
 
Reference 22 does not show that adenocarcinoma has poorer survival than SCC. On the contrary 
the study finds that ACC has better survival than SCC because less of it is diagnosed at very 
advanced stages.  
 
Line 228 -234: natural history of cervical cancer i s the reason why diagnosis increase with age 
while the same is not found in precancerous lesions. This has nothing to do with screening. In 
fact where screening programmes are well established the age specific incidence of cervical 
cancer is shifted toward s earlier ages (http://www.wolfson.qmul.ac.uk/centre -reports/centre -for-
cancer -prevention). Although cervical cancer is occasionally diagnosed in very young women 
screening with a pap smear is not recommended in those under age 20 (some argue 25) and is 
better in older women suggesting that intervals can be extended to every 5 years after age 50. 
The introduction of primary HPV testing has led some to call for screening to start at age 30 with 
a frequency of every 5 years at all ages.  
 
Conclusions: line 265 should read "symptomatic" rather than "asymptomatic"  
 
Are the methods appropriate and wel l 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.  
 
Yes 
 
Are the conclusions drawn ad equately 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:  
 
Needs some language corrections before being published  
 
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 fr om an 
organisation that may in any way gain or lose financially from the publication of this 
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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 f or 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?  
 
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below. If your reply is yes to any, please give details below.  
 
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