Cervical cancer is one of the most common cancers in women and one of the leading causes
of death in women worldwide. Pre-cancerous lesions (dysplasias) are detected by the
preventive smear test at the gynecologist and can thus contribute to a 100% chance of
cure if they are clarified by a colposcopic examination as part of the dysplasia
consultation and dysplastic lesions are then surgically removed if necessary
(conization).
In practice, there are four different methods by which conization can be performed: Knife
Conization, Laser Conization, Large Loop Excision of the Transformation Zone (LLETZ) and
Loop Electrical Excision Procedure (LEEP). The first three methods have in common that
they aim to remove the entire transformation zone. The rationale for this is that both
the precancerous lesions and the cervical carcinoma itself originate in the
transformation zone of the cervix. This thesis would support the idea of resecting the
lesion while taking the remaining healthy transformation zone along as a precaution.
However, it is clear that with the removal of the entire transformation zone, healthy
tissue is removed in addition to the lesion itself. Any increase in radicality may
increase the complication rate of the procedure, especially with regard to the most
feared long-term complication of preterm birth, because the more cervical tissue is
removed, the higher the risk of subsequent preterm birth. This connection speaks in favor
of the use of LEEP, in which only the visible dysplastic tissue in healthy tissue is
removed in the sense of a radical resection, without at the same time also removing the
entire transformation zone, especially in women who still wish to have children.
In summary, the aim of conization is on the one hand to achieve a high level of
oncological safety (low recurrence rate, high R0 resection rate) by resecting sufficient
dysplastic tissue, and on the other hand to avoid excessive tissue resection, because
this would increase the risk of premature birth in a subsequent pregnancy.
There is no direct head-to-head comparison between LEEP and LLETZ in the literature
regarding oncologic safety, for which complete resection of the dysplastic lesion
(so-called 'in-sano resection') is the most appropriate postoperative surrogate
parameter. In a Pubmed literature search (search date: February 10, 2021, search terms:
conization, LEEP, LLETZ, resection margin, randomized), no prospective randomized study
on this topic was found. Further clinical studies are therefore useful to optimize
surgical therapy for cervical dysplasia
The primary objective of the present study is to compare LLETZ (resection of the
dysplastic lesion including the transformation zone) with targeted resection of the
colposcopically conspicuous lesion only (LEEP) and to compare it with regard to
oncological safety (defined as non-in-sano rate).
For this purpose, patients with histologically confirmed CIN II/III will be randomly
assigned to one of the two surgical methods. In order to exclude an unwanted influence by
unconsciously different behavior of the patients, the patient will only learn about the
surgical method performed on her after the control examination 6 months postoperatively
(unilateral blinding). The surgeon is not blinded for obvious technical reasons. However,
in case of complications, access to the surgical report and the chosen method is possible
at any time.
Immediately postoperatively, the specimen is examined histologically and evaluated with
regard to the depth of the conus and the degree of dysplasia as well as the resection
margins (R0= free resection margin; R1= dysplasia extends to the resection margin) by a
pathology specialist.
After an interval of 6-8 months, the first follow-up examination (the so-called "test of
cure") with PAP smear and HPV test is performed in accordance with the guidelines. The
two groups are compared with regard to normalization of the Pap smear, HPV status and
colposcopic findings (including histology in the case of colposcopic abnormalities).
For patients with negative HPV test, unremarkable cytology, histology and colposcopy, the
study is terminated. These patients are considered cured and discharged to regular
screening with their established gynecologist. In case of abnormalities, the further
procedure is determined according to the usual clinical criteria in conformity with the
guidelines: clinical control after 3 and/or 6 months or re-conization.
Secondary target criteria of the study are, in addition to the intra- and postoperative
complication rate, the pain perception of the patients and the intraoperative blood loss,
also the rate of negative high risk HPV tests after 6-8 months, since a negative HPV test
is generally regarded as evidence of successful treatment. Thus, the negative predictive
value for a negative HPV test after conization ranges from 92% to 100%. Successful
therapy usually results in elimination of the HP virus. Accordingly, a negative HPV test
excludes CIN persistence or recurrence with a high probability. In contrast, a
persistently positive HPV test may be taken as an indication of persistence of dysplasia
or as an indicator of recurrent dysplasia.