Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia
Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia
Cervical dysplasia is the precursor of cervical cancer. LEEP and LLETZ are standard surgical
 procedures to treat cervical dysplasia. 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. 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).
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.
Inclusion Criteria:

 -  Histologically confirmed High Grade Squamous Intraepithelial Lesion (HSIL)

 -  Colposcopically visible lesion

 -  No therapy of the disease so far

 Exclusion Criteria:

 -  Pregnancy of the patient at/after inclusion in the study; pregnancy after conization
 and before the control after 6 months is possible and does not lead to exclusion from
 the study.

 -  Taking immunosuppressive drugs (incl. glucocorticoids)

 -  Known HIV positivity

 -  Malignant disease requiring treatment

 -  Unsatisfactory colposcopy