iMproving thE DIagnostics And Treatment Of ceRvical Precancer

Cervical Cancer Clinical Trial

— MEDIATOR  

Official title:

iMproving thE DIagnostics And Treatment Of ceRvical Precancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05870787
• Other study ID #: 2022-0367531-3031
• Status: Recruiting
• Start date: March 1, 2023
• Est. completion date: August 1, 2026

Study information

• Verified date: June 2024
• Source: University of Aarhus
• Contact: Ane-Kersti Knudsen, MD,Ph.d.stud
• Phone: +78430000
• Email: ane.kersti[@]midt.rm.dk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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 purpose is:

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

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

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 improve diagnostic accuracy of cervical lesions with detection of CIN2+ in a Danish clinical setting. Furthermore, we want to evaluate whether the Swede score can be used to assess when 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1066
• Est. completion date: August 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 23 Years to 99 Years

Eligibility

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 cone biopsy, hysterectomy or without a cervix due to cervical cancer will be excluded.

• Pregnant women.

Related Conditions & MeSH terms

• Cervical Cancer
• Cervical Disease
• Cervical Dysplasia
• Cervical Lesion
• Cervical Neoplasm
• Uterine Cervical Diseases
• Uterine Cervical Dysplasia
• Uterine Cervical Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Denmark	Guldberg Kvindeklinik	Fredericia
Denmark	Gødstrup Regional Hospital	Herning
Denmark	Horsens Gynækologisk Klinik	Horsens
Denmark	Horsens Regional Hospital	Horsens
Denmark	Odense Univeristy Hospital	Odense
Denmark	Randers Regional Hospital	Randers
Denmark	Viborg Regional Hospital	Viborg

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosis of collected cervical biopsies	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