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Cervical DysplasiaLLETZ-IOLINCT05132114

Large Loop Excision of the Transformation Zone (LLETZ) With vs Without IntraOperative Application of Lugol's Iodine

A study testing Lugol's iodine test in people with Cervical Dysplasia, run by Ruhr University of Bochum at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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 gynecologist's preventive smear test and can thus contribute to a 100% chance of cure if they are clarified by a colposcopic examination as part… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cervical Dysplasia
What is being tested?
Lugol's iodine test
Could I receive a placebo?
No, everyone receives an active treatment
How many people
230 participants
Where
1 siteGermany
Study dates
17 Jan 2022to 16 Oct 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written consent
  • Colposcopy performed preoperatively
  • Histologically (by previously performed colposcopy) confirmed dysplasia (CIN 1, CIN 2 or CIN 3)
  • Diagnostic LEEP after abnormal cytology and inconclusive colposcopy
  • HPV persistence (on patient request)
  • Age >=18 years

Who cannot join

  • Pregnant patients
  • Patients with insufficient knowledge of the German language
  • Treatments already performed on the cervix uteri, in particular conization
  • Blood coagulation disorders
  • Taking blood thinning substances
  • Iodine allergy

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Marien Hospital Herne

    Herne, North Rhine-Westphalia, 44625

Other trials in Germany

About this study

Official title: Large Loop Excision of the Transformation Zone (LLETZ) With Versus Without Intraoperative Application of Lugol's Iodine in Women With Cervical Dysplasia: a Prospective Randomized Trial

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 gynecologist's preventive smear test 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, if necessary, surgically removed. Conization (= surgical removal of a cone of tissue from the cervix) is the method of choice for removing the diseased tissue. LLETZ conization (Large Loop Excision of the Transformation Zone) is the worldwide standard surgical procedure for conization. There is risk of local persistence of the precancerous lesion if the cervical dysplasia is not completely removed. To minimize this, the iodine test can be used. Here, a 5% iodine solution (so-called Lugol's solution) is dabbed onto the cervix uteri, resulting in an intense and characteristic brown staining of the healthy cervical epithelium. Sites without staining are termed iodine negative and may contain dysplastic cells. The strength of iodine testing lies in its high specificity, i.e., the reliable ability to exclude false-positive results. The purpose of intraoperative iodine staining is to select the resection line with a high degree of certainty in healthy (i.e., iodine-positive) tissue in order to reduce the rate of cervical dysplasia that is not completely removed (so-called non-in-sano resection, or R1 resection). Systematic survey data from the dysplasia units certified in Germany on the question of the use of intraoperative iodine testing in Germany are lacking, as is the literature as a whole. For example, the current S3 guideline of the German Society of Gynecology and Obstetrics on the diagnosis and treatment of cervical dysplasia (as of March 2020) names intraoperative iodine testing only as a possible option for performing LLETZ.

In this prospective, randomized study, the investigators aim to answer the question whether LLETZ performed with the help of an iodine test with selection of the resection line in the iodine-positive area leads to a lower rate of R1 resections compared to the standard LLETZ without iodine test.

Read the detailed description
  1. Background 1.1. HPV and dysplasias of the cervix uteri Human papillomaviruses (HPV) are the most common sexually transmitted pathogens worldwide. The prevalence in both male and female populations is high. Epidemiological estimates suggest that 85-91% of sexually active adults acquire at least one genital HPV infection by the age of 50, with approximately 95% of HPV infections being spontaneously eliminated within 2 years in terms of HPV immunological clearance. HPV preferentially infects the epithelial cells of the anogenital area and, through incorporation of HPV DNA into the host genome of the basal cells of the squamous epithelium of the cervix and subsequent expression of viral components, causes dysplastic changes in the cervical epithelium that, if left untreated, can develop into invasive carcinoma of the cervix (cervical carcinoma). Cervical carcinoma is the fourth most common cancer as well as the fourth leading cause of cancer-related death in women worldwide, responsible for 6.6% (570,000) of all new cancer cases and 7.5% (311,000) of cancer-related deaths in women in 2018. The precursor of squamous cell carcinoma of the uterine cervix (approximately 80% of all cervical cancers) is cervical intraepithelial neoplasia (CIN), which has three grades of expression (CIN1, CIN 2, and CIN 3). Compared with invasive cervical carcinoma, the incidence of precancerous lesions of the cervix uteri is much higher. It is estimated that approximately 100,000 women in Germany develop high-grade dysplasia (CIN2/CIN3) annually. 1.2. Surgical treatment If precancerous lesions with the potential to develop into an invasive cervical tumor are detected, conization (= surgical removal of a cone of tissue from the cervix) is the method of choice for removing the diseased tissue. Worldwide standard as surgical procedure for conization is LLETZ-conization (Large Loop Excision of the Transformation Zone). In addition to the risk of local persistence of the precancerous lesion if the cervical dysplasia is incompletely removed, LLETZ also increases the risk of preterm birth in a subsequent pregnancy. This risk increases with increasing volume of removed tissue. To reduce or avoid the aforementioned complications, conization should be performed under colposcopic vision and as little healthy cervical tissue as possible should be removed. One method of LLETZ that is as tissue-conserving as possible is the intraoperative use of the so-called 'iodine test'. 1.3. The iodine test For the identification of healthy squamous epithelium of the cervix uteri, the so-called Schiller's iodine test can be used, which has been part of the clinical routine in the context of colposcopy of cervical dysplasias for decades. In the iodine test, a 5% iodine solution (so-called Lugol's solution) is dabbed onto the cervix uteri, resulting in an intense and characteristic brown staining of the healthy cervical epithelium. Sites without staining are termed iodine negative and may contain dysplastic cells. The strength of iodine testing lies in its high specificity, i.e., the reliable ability to exclude false-positive results. Not all iodine-negative areas contain CIN, but iodine-positive areas are almost certainly healthy. In some centers, because of these characteristics of the iodine sample, it is used during LLETZ to define the resection line of LLETZ. The aim of this approach is to select the resection line with a high degree of certainty in healthy (i.e., iodine-positive) tissue in order to reduce the rate of cervical dysplasia that is not completely removed (so-called 'non-in-sano resection' or 'R1 resection'). Systematic survey data from the dysplasia units certified in Germany on the question of the use of intraoperative iodine testing in Germany are lacking. The current S3 guideline of the German Society of Gynecology and Obstetrics on the diagnosis and therapy of cervical dysplasia (as of March 2020) also refers to intraoperative iodine testing as a possible option for performing LLETZ. However, exact figures from controlled studies on the usefulness of iodine test-guided LLETZ are lacking in the literature (PubMed search on 10/15/2021; search terms: cervical dysplasia, colposcopy, Lugol's test, iodine test, Lugol's staining; LLETZ; LEEP; conization). At our certified dysplasia center, it is the decision of the respective surgeon whether an additional intraoperative iodine test is performed or not.
  2. Aim of the study The aim of this study is to answer the question under prospective randomized conditions whether LLETZ performed with the aid of iodine assay with selection of the resection line in the iodine-positive region leads to a lower rate of R1 resections compared with standard LLETZ without iodine assay.
Being tested
Lugol's iodine test
Keywords
cervical dyslasia, LLETZ, LEEP, Lugol's iodine, conization
Medical subject headings
Uterine Cervical Dysplasia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lugol's iodine testDiagnostic test

    Intraoperative application of Lugol's iodine (i.e. staining of the cervix with Lugol's iodine solution)

Study groups in NCT05132114
Study groupRoleWhat they receive
Control GroupNo interventionLLETZ (without intraoperative Lugol's iodine)
Iodine groupExperimentalLLETZ after the intraoperative application of Lugol's iodine
Receives: Diagnostic Test: Lugol's iodine test

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of R1 resections

    The primary outcome parameter is the rate of R1 resections, defined as the presence of dysplastic (CIN I, CIN II, CIN III, AIS) or malignant cells at the ectocervical and/or endocervical resection margin, as indicated in the histopathologic report.

    Measured: Specimen from surgery (result expected 1-2 days after surgery)

Secondary outcomes (10)

  1. Cone mass

    The weight of the cone specimen (measured in grams in the unfixed state)

    Measured: During surgery, immediately after the excision

  2. Procedure duration

    Duration of the procedure (from start until complete hemostasis is achieved)

    Measured: At surgery

  3. Rate of complications

    The occurring intra- and postoperative complications in a period within 14 days after surgery

    Measured: During surgery up to 14 days post surgery

  4. Surgeon's rating of handling

    The assessment of the surgeon's handling of the surgical technique (LLETZ with/without intraoperative iodine assay) (11-item numerical rating scale [NRS]; 0 = very cumbersome, 10 = very easy)

    Measured: Immediately after surgery

  5. Surgeon's satisfaction

    The surgeon's satisfaction with the course of the operation in general (11-item NRS; 0 = no satisfied at all, 10 = very satisfied)

    Measured: Immediately after surgery

  6. Time to complete hemostasis

    The time from start of electro-coagulation until complete hemostasis (seconds)

    Measured: During surgery

  7. Blood loss

    The intraoperative blood loss (measured as the difference between preoperative and 3-5 hours postoperative Hb levels).

    Measured: At surgery

  8. Pain (patient-reported)

    Pain (0 = no pain, 10 = worst pain)

    Measured: Immediately after surgery

  9. Overall patient satisfaction (patient-reported)

    Overall satisfaction with treatment (0 = not satisfied, 10 = maximally satisfied)

    Measured: Immediately after surgery

  10. 14-day post-intervention questionnaire (patient-reported)

    Questionnaire asking

    • Pain (during first 24h after surgery; 0-10)
    • Duration of pain (days)
    • Use of analgesics (y/n)
    • Bleeding intensity (during first 24h after surgery; 0 no bleeding - 10 intensive bleeding)
    • Bleeding duration (days)
    • Overall satisfaction (0-10) (same scales as in Outcomes 9 and 10)

    Measured: 14 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2021
  2. Study start17 Jan 2022
  3. Primary completion25 Sep 2025
  4. Study completion16 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective randomized trial with 2 groups (use vs not use of Lugol's iodine during LLETZ)
Masking
Single blind
Who is masked
Participant
Enrolment
230 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05132114
Sponsor's protocol ID
LLETZ-IOLI-1
Acronym
LLETZ-IOLI
Status last verified
Oct 2026
First submitted
11 Nov 2021
Last updated
16 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data will be shared upon reasonable request made to the corresponding author. This includes individual participant data underlying the results presented here, after deidentification, as well as data dictionaries and the the study protocol. Data is available after publication, without a specific end date. Requesting investigators must show that their proposed use of the data has been approved by an independent review committee identified for this purpose.

Publications

  • Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187. doi: 10.15585/mmwr.rr7004a1.

    PubMed 34292926

  • Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014 Nov;41(11):660-4. doi: 10.1097/OLQ.0000000000000193.

    PubMed 25299412

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PubMed 30207593

  • Mathevet P, Chemali E, Roy M, Dargent D. Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP. Eur J Obstet Gynecol Reprod Biol. 2003 Feb 10;106(2):214-8. doi: 10.1016/s0301-2115(02)00245-2.

    PubMed 12551795

  • Bevis KS, Biggio JR. Cervical conization and the risk of preterm delivery. Am J Obstet Gynecol. 2011 Jul;205(1):19-27. doi: 10.1016/j.ajog.2011.01.003. Epub 2011 Feb 23.

    PubMed 21345402

  • Jin G, LanLan Z, Li C, Dan Z. Pregnancy outcome following loop electrosurgical excision procedure (LEEP) a systematic review and meta-analysis. Arch Gynecol Obstet. 2014 Jan;289(1):85-99. doi: 10.1007/s00404-013-2955-0. Epub 2013 Jul 11.

    PubMed 23843155

  • Khalid S, Dimitriou E, Conroy R, Paraskevaidis E, Kyrgiou M, Harrity C, Arbyn M, Prendiville W. The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity. BJOG. 2012 May;119(6):685-91. doi: 10.1111/j.1471-0528.2011.03252.x. Epub 2012 Feb 14.

    PubMed 22329499

  • Shaco-Levy R, Eger G, Dreiher J, Benharroch D, Meirovitz M. Positive margin status in uterine cervix cone specimens is associated with persistent/recurrent high-grade dysplasia. Int J Gynecol Pathol. 2014 Jan;33(1):83-8. doi: 10.1097/PGP.0b013e3182763158.

    PubMed 24300540

  • Preaubert L, Gondry J, Mancini J, Chevreau J, Lamblin G, Atallah A, Lavoue V, Caradec C, Baldauf JJ, Bryand A, Henno S, Villeret J, Agostini A, Douvier S, Jarniat A, Riethmuller D, Mendel A, Brun JL, Rakotomahenina H, Carcopino X. Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study. J Low Genit Tract Dis. 2016 Jan;20(1):15-21. doi: 10.1097/LGT.0000000000000156.

    PubMed 26704328

  • Kuhn W. [Colposcopy in the diagnosis of early cervical cancer]. Pathologe. 2011 Nov;32(6):497-504. doi: 10.1007/s00292-011-1480-9. German.

    PubMed 21984389

  • Hilal Z, Rezniczek GA, Alici F, Kumpernatz A, Dogan A, Alieva L, Tempfer CB. Loop electrosurgical excision procedure with or without intraoperative colposcopy: a randomized trial. Am J Obstet Gynecol. 2018 Oct;219(4):377.e1-377.e7. doi: 10.1016/j.ajog.2018.07.023. Epub 2018 Jul 29.

    PubMed 30063903

  • Rezniczek GA, Hecken JM, Rehman S, Dogan A, Tempfer CB, Hilal Z. Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial. Am J Obstet Gynecol. 2020 Dec;223(6):888.e1-888.e9. doi: 10.1016/j.ajog.2020.06.041. Epub 2020 Jul 24.

    PubMed 32585223

  • Hilal Z, Rezniczek GA, El-Fizazi N, Tempfer CB. Large Loop Excision of the Transformation Zone Versus True Cone Biopsy Electrode Excision: A Randomized Trial. J Low Genit Tract Dis. 2017 Oct;21(4):272-278. doi: 10.1097/LGT.0000000000000329.

    PubMed 28953118

Questions about this trial

What is this clinical trial studying?

A study testing Lugol's iodine test in people with Cervical Dysplasia, run by Ruhr University of Bochum at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of R1 resections (time frame: Specimen from surgery (result expected 1-2 days after surgery)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05132114, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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