iMproving thE DIagnostics And Treatment Of ceRvical Precancer

NCT ID: NCT05870787

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 929 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2024-12-13

Brief Summary

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.

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.

Conditions

Cervical Dysplasia; Cervical Disease; Cervical Lesion; Cervical Cancer; Cervical Neoplasm

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Swede score colposcopy

Intervention Type: DIAGNOSTIC_TEST

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.

No interventions assigned to this group

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 23 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Hammer, MD, as.prof

Role: STUDY_CHAIR

University of Aarhus

Ulrik Schiøler Kesmodel, MD, prof

Role: STUDY_CHAIR

Aalborg University Hospital

Berit Bargum Booth, MD, Ph.d.

Role: STUDY_CHAIR

Randers Regional Hospital

Line Winther Gustafson, MD, Ph.d.

Role: STUDY_CHAIR

Aarhus University Hospital

Locations

Guldberg Kvindeklinik

Fredericia, Fredericia, Denmark

Gødstrup Regional Hospital

Herning, Herning, Denmark

Horsens Gynækologisk Klinik

Horsens, Horsens, Denmark

Horsens Regional Hospital

Horsens, Horsens, Denmark

Odense Univeristy Hospital

Odense, Odense, Denmark

Randers Regional Hospital

Randers, Randers, Denmark

Viborg Regional Hospital

Viborg, Viborg, Denmark

Countries

Denmark

References

Knudsen AS, Randrup TH, Kesmodel US, Booth B, Gustafson L, Trope A, Strander B, Nieminen P, Hammer A. Assessment of a colposcopic scoring system (Swedescore) to reduce the number of cervical biopsies: a protocol for a clinical multicentre non-randomised intervention study in Denmark. BMJ Open. 2024 Dec 15;14(12):e085382. doi: 10.1136/bmjopen-2024-085382.

Reference Type: DERIVED

PMID: 39675832 (View on PubMed)

Other Identifiers

2022-0367531-3031

Identifier Type: -

Identifier Source: org_study_id