iMproving thE DIagnostics And Treatment Of ceRvical Precancer (MEDIATOR)

February 5, 2026 updated by: University of Aarhus

Cervical cancer screening is important as it enables identification of women at increased risk of the disease, but high-quality diagnostics of screen-positive women and effective treatment of those with precancer are critical in preventing progression to cancer. With the current transition from cytology-based to primary human papillomavirus (HPV)-screening and a growing proportion of HPV-vaccinated women, diagnostics of screen-positive women will become more challenging in the decades to come. Thus, there is a need to explore how to improve diagnostics while ensuring a low number of unnecessary procedures such as colposcopy and the collection of multiple cervical biopsies.

The overall purposes are:

Purpose 1: To investigate the diagnostic accuracy of cervical precancer when using a colposcopic scoring system in the diagnostic work-up of screen-positive women.

Purpose 2: To investigate the performance of a colposcopic scoring system to identify women without cervical precancer in whom collection of biopsies can be safely omitted.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction Cervical cancer is the fourth most common cancer in women worldwide. Every year, 375 women are diagnosed with cervical cancer in Denmark, and approximately 90 women die from the disease. Cervical cancer is caused by the sexually transmitted virus, human papillomavirus (HPV). When infected about 85-90 % clear the virus within a year or two. The remaining women develop a persistent HPV infection, which is associated with an increased risk of cervical intraepithelial neoplasia (CIN), which may progress to cancer if left untreated. Cervical cancer can be prevented through prophylactic HPV vaccination and screening. In Denmark, women aged 23 - 64 years are invited to the screening program. Women who do not participate in regular screening have an increased risk of cervical cancer, however up to 55% of cervical cancers are diagnosed in women who have attended screening. Hence, the performance of diagnostics is crucial.

Diagnostics Women with abnormal screening results may undergo repeat testing or be referred for colposcopy. Colposcopy allows the colposcopist to magnify and visualize the cervix with the transformation zone, where cervical cancer and cervical lesions typically arise. The aim is to make a colposcopic diagnosis and select the most severe area for biopsies, which undergo histopathological examination. Studies have shown considerable inter- and intra-observer variability even among experienced colposcopists, and a variable sensitivity of colposcopy as low as 55-57%. These findings suggest a need to improve the detection rate of CIN2+. A validated colposcopic scoring system, the Swede score, has been designed to improve the detection of high-grade cervical lesions, specified as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by providing an systematic approach to the colposcopy examination. The Swede score includes five variables (degree of 1) acetowhitening, 2) margins and surface, 3) vessels, 4) lesion size, and 5) iodine staining by using Lugols iodine) with a score from 0 - 2. Conventional colposcopy only utilizes acetic acid. In the original study, the Swede score had a high sensitivity and specificity for detecting high-grade cervical lesions (CIN2+), with an area under the receiver operating characteristics (ROC) curve of 0.87. Even so, the Swede score is endorsed by the International Agency for Research on Cancer (IARC/WHO) and by the European Federation for Colposcopy (EFC), it has not yet been implemented in Denmark. As previous studies have mostly evaluated the use of the Swede score among expert colposcopists, it is important to assess whether the score may be a valuable tool among non-experts. In Denmark, colposcopy is mostly performed by non-experts gynecologists. As a result of the low performance of colposcopy, and because several studies have shown that the CIN2+ detection rate increases with the number of biopsies collected, the Danish national guidelines recommend that all women should have a minimum of 4 biopsies collected. Biopsies should be collected from abnormal areas of the cervix and, if no lesion is detected, random biopsies should be taken. Our neighboring Scandinavian countries, for example Sweden and Finland, do not recommend collection of random biopsies. If biopsies could be omitted without increasing the risk of missing disease and reducing the harms with pain, bleeding and discomfort, this would benefit the women.

Aim

The project aims to explore whether the implementation of a systematic colposcopic scoring system, the Swede score, can:

Pupose 1: Improve diagnostic accuracy of cervical lesions with detection of CIN2+ in a Danish clinical setting.

Purpose 2: Evaluate whether the Swede score can be used to assess cervical lesions with <CIN1, so random biopsies can be safely omitted.

Data Characteristics of the women will be collected from medical records (previous gynecological historic, parity, smoking status, HPV-vaccination status, hormone use or immunosuppressive treatment). From the Danish Pathology Databank, we will collect data on previous screening history, result of the referral screening test, result of current and subsequent cervical biopsies and/or cervical excision.

Study Type

Observational

Enrollment (Actual)

929

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Fredericia
      • Fredericia, Fredericia, Denmark, 7000
        • Guldberg Kvindeklinik
    • Herning
      • Herning, Herning, Denmark, 7400
        • Gødstrup Regional Hospital
    • Horsens
      • Horsens, Horsens, Denmark, 8700
        • Horsens Gynækologisk Klinik
      • Horsens, Horsens, Denmark, 8700
        • Horsens Regional Hospital
    • Odense
      • Odense, Odense, Denmark, 5000
        • odense univeristy hospital
    • Randers
      • Randers, Randers, Denmark, 8900
        • Randers Regional Hospital
    • Viborg
      • Viborg, Viborg, Denmark, 8800
        • Viborg Regional Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Women with abnormal smear (HPV-genotype and cytology) referred to colposcopy, visibel transformation zone (type 1 or 2) and where cervical biopsies has been sent to pathology examination.

Description

Inclusion Criteria:

  • Women referred to colposcopy due to abnormal smear (HPV-genotype and cytology) in Central Denmark Region or Southern Denmark Region.

Exclusion Criteria:

  • Allergic to iodine.
  • Tranformationzone not visible (type 3).
  • Atrophy of cervical epithelium.
  • Women referred to colposcopy with no cervical biopsies taken or invalid cervical biopsies.
  • Women with previous hysterectomy or without a cervix due to cervical cancer will be excluded.
  • Pregnant women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Swede score colposcopy
Swede score colposcopy: includes application with acetic acid, supplemented with a systematic scoring system (the Swede score) including Lugols iodine, and collection of cervical biopsies.
Diagnostic test: Swede score colposcopy
New colposcopy method: with application of acetic acid, supplemented with a systematic scoringsystem (Swede score) including Lugols iodine, and collection of cervical biopsies.
Conventional colposcopy
Conventional colposcopy: includes application with acetic acid and collection of cervical biopsies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Purpose 1: Diagnosis of collected targeted cervical biopsies
Time Frame: When the histological report is available - typically within 12 weeks after the biopsy was taken
The number of women diagnosed with Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) diagnosed in cervical biopsies
When the histological report is available - typically within 12 weeks after the biopsy was taken
Purpose 2: Diagnosis of collected random cervical biopsies
Time Frame: When the histological report is available - typically within 12 weeks after the biopsy was taken

The number of women diagnosed with Cervical Intraepithelial Neoplasia grade 1 or less (<CIN1) vs. (CIN2+) diagnosed in random cervical biopsies.

The clinical perspectives will be the absolute risk of CIN2+ in random biopsies.
When the histological report is available - typically within 12 weeks after the biopsy was taken

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Study Chair: Anne Hammer, MD, as.prof, University of Aarhus
  • Study Chair: Ulrik Schiøler Kesmodel, MD, prof, Aalborg University Hospital
  • Study Chair: Line Winther Gustafson, MD, Ph.d., Aarhus University Hospital
  • Study Chair: Berit Bargum Booth, MD, Ph.d., Randers Regional Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2023

Primary Completion (Actual)

December 6, 2024

Study Completion (Actual)

December 13, 2024

Study Registration Dates

First Submitted

May 12, 2023

First Submitted That Met QC Criteria

May 12, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

February 10, 2026

Last Update Submitted That Met QC Criteria

February 5, 2026

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-0367531-3031

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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