Title: Can biopsies be omitted after normal colposcopy in women referred with low-grade
cervical cytology? A prospective cohort study.
Version: 2 Date: 07 May 2021
Reviewer:  Margaret Cruickshank
Reviewer's report:
The effectiveness and need for so called 'blind biopsies' or rather sampling of colposcopically
normal transformation zone of the cervix to ensure clinically significant disease is not missed
with the inherent risk of a woman going on to develop cancer if it remains undetected, continues
to provoke debate.  indeed, it is concerns about the limitations of colposcopy and ability to
identify high grade CIN that has added weight to the move to adjuncts to colposcopy.
This study looks at 4 quadrant sampling of women seen at colposcopy with low grade cytology
and 'normal colposcopy'. these are well described in clinical information .
There are 2 very different populations of women - those who are new referrals from screening
and those who have previously been treated for 'dysplasia'.  This means that not only has their
transformation zone been excised or ablated in the past but if this dysplasia was high grade CIN
that they are in a different and well recognised category or risk.
The definition of normal colposcopy is not clear as in one part it says that there is is no
abnormality but in 2 others that this can include acetowhiteing, abnormal vessels and capillary
vessel patterns.  This definition of normality is referenced to 1984 paper on Reid score and 2005
paper on Swede score.  Whilst in these scoring systems where such features do not (except for
abnormal vessels which are a major finding) attract a point, this is in the context of a total score
which is used to predict the probable histology but I feel to state that these are normal findings
is too reductive.
196 women had normal colposcopy and it would be interesting to know about the 23 with
no biopsy and if there is any follow up data.  Givent he age up to 79 Years, information on
transformation zone types will help as colposcopy can only be considered normal if the whole
of the TZ (type 1 or 2) can be inspected.  Otherwise it is not possible to confirm normality. Even
if biopsies from women with a type 3 TZ showed TZ sampling, this is only blind sampling. I am
concerned in the discussion that the authors recommend punch biopsies with a type 3 TZ whilst
most guidance recommends excision of TZ if HG disease is suspected.
The ALTS study is referenced but not TOMBOLA, the UK equivalent, where women with a
normal colposcopy had a low risk of CIN2+ being detected by 3 years of follow-up.  This brings
me back to my original point about detecting clinically significant disease that could become
a cancer by next follow-up or if the woman defaults by next follow up.  In TOMBOLA, by
3 year colposcopy assessment if CIN2+ lesions were missed at initial colposcopy, these may
have regressed and meant the woman avoided unnecessary biopsies and treatment.  although the
paper says these are CIN2+ cases who 'warrent treatment' increasingly women with CIN2 are
managed conservatively so it would be of more interest to separate CIN3+ cases from CIN2.
I wonder if the number of biopsies taken is a confounder in particular if colposcopic features
such as acetowhtening and capillary vessel patterns are considered normal.  Could women with
large 'normal' lesions have more biopsies taken than women who had no colposcopic features?