Title: Extensive lesions and a positive cone margin are strong predictors of residual disease in
subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3
Study design Retrospective study
Version: 1 Date: 08 Jun 2023
Reviewer's report:
Review  –  BMJ Women Health
Title
Extensive lesions and a positive cone margin are strong predictors of residual disease in
subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3
Review result:
First: an article of this scope with this content is better suited to a local magazine than a
prestigious magazine with an international impact.
Second: I find this article a bit confusing in its content and writing style. Some things are unclear.
Why there was such a short interval between conization and hysterectomy (median 5 days)?
On the other hand, the longest interval was 192 days. Why were there so many CKCs and few
LEEPs?
Why did you not use other electrosurgical procedures with needle (NETZ) or a triangle-shaped
instrument? What kinds of hysterectomies were performed? How is it possible that AIS and
microinvasive carcinoma were not recognized from histological examination from conization?
How big and deep was the cone and what effect did it have on residual disease? Tables are
incomplete - missing % for most, missing OR for positive margins (which is written in the text).
I leave it to the editor's discretion whether it makes sense to do a review again after major revision
of the article.
Page 4
lines 97-99:   Women with incomplete clinical data were excluded from analysis. This study
conforms to the provisions of the Declaration of Helsinki (as revised in Tokyo 2004).
Note:  A citation should be added.
Page 5
lines 121-122: The median interval from conization to hysterectomy was 5 days (range: 1–192
days).
Note:  Was the median time  from conization to hysterectomy really 5 days? How long did
you wait for the final histological result incuding imunostaining? What was the indication
for hysterectomy one day after conisation? Such a short intervat is really strange. It shoul be
explained in detail.
Page 6
lines 126-127: Type I or II was observed in 210 patients (78.7%).
Note: Type I or II of what?
Page 6
lines 133-134: The pathological results of conization indicated that EGI was present in
175(65.2%) patients and that 83(30.7%) patients had a positive resection margin.
Note: The number of positive endocervical and ectocervical margins should be mentioned.
Page 6
lines 134-137: Following hysterectomy, 197 (73.8%) patients exhibited no evidence of CIN 2/3,
whereas three (1.1%) patients were found to have previously undiagnosed cervical cancer (two
patients with adenocarcinoma in situ and one with microinvasive carcinoma).
Note: Adenocarcinoma in situ IS NOT previously undiagnosed cervical cancer. What kind od
carcinoma and how deep was the invasion? How is it possible that AIS and microinvasive
carcinoma were not recognized from histological examination from conization?
Page 7
lines 155-158: The risk of residual CIN 2/3 or worse varied according to the anatomical
localization of the margin (endocervical margin: OR, 10.985[95% CI, 4.677-25.804];
ectocervical margin: OR, 7.632[95% CI, 3.685-15.805]; for both endo- and ectocervical:
residual lesions were found in all nine patients).
Note: The abbreviation OR should be explained.  The ORs for endo- and ectocervical positive
margins are shown in any Table?
Page 7
lines 161-162: In present study confirmed that margin involvement and extensive lesions were
predictors of residual lesions in hysterectomy specimens
Note: Probably -  In present WAS study confirmed ….
.
Page 8
lines 183-183: Moreover, residual lesions at the edges of the cervix after conization may be
eliminated by rapid cell turnover during cervical healing and by vaginal acidity.
Note:  A citation should be added.
Page 11
Lines: 243-244: In particular, we found no significant differences in menopausal status, type of
TZ, gravidity, parity, and conization method.
Note: The representation of CKC (91.4%) and LEEP (8.6%) was very uneven. Why didn't you
perform more LEEPs?
Table 1
A total number of subjects is missisng. A % value should be added (where it makes sense)
Table 2
The same - A total number of subjects is missisng. A % value should be added
Table 3
A total number of subjects is missisng. A % value should be added (where it makes sense).
Margin status should be mentioned in more detail – ecto vs endo, especially p-value difference
for residual lesion between positive ecto and endo.
In addition, you write in the Discussion (Lines 167-169): Specifically, the endocervical margin
status has been recognized to be significant, whereas the exocervical margin status remains
controversial [15-20]