Trial23 - A Method Study on Cervical Screening in Women Offered HPV-vaccination as Girls

November 3, 2022 updated by: Elsebeth Lynges, University of Copenhagen

Trial23 - A Method Study on the Use of Primary HPV-testing With Cytology Triage in Women Offered HPV-vaccination as Girls

In Denmark, the first birth cohorts of women offered HPV-vaccination as girls are entering the cervical screening program. These women are expected to be better protected against cervical cancer. It has not yet been decided how to screen these women.

This method study will investigate a possible screening scheme that could provide a reduced burden of screening for HPV-vaccinated birth cohorts.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

In Denmark, women aged 23-49 are offered cervical screening with liquid-based cytology (LBC) every 3rd year, and women aged 50-59 every 5th year. Women aged 60-64 are offered an exit HPV-DNA test.

In 2008 vaccination against Human papilloma virus (HPV) was offered free of charge to girls aged 13-15. HPV-vaccination has been part of the child vaccination program for 12-year old girls since 2009. Women born in 1994 were offered HPV-vaccination at age 14, and approximately 80% are HPV-vaccinated. These women entered the screening program in 2017.

HPV-testing is shown to provide a better protection against cervical cancer than cytology testing, and the 6-year protection against CIN3+ after a negative HPV-test has been observed to be higher than the 3-year protection after a negative cytology test (ref).

The aim of the study is to evaluate if primary screening with HPV-testing and LBC triage every 6 years in women offered HPV-vaccination as girls would provide at least the same protection as the present screening, measured by cumulative number of cervical intraepithelial neoplasia (CIN). This screening scheme would allow HPV-negative women to benefit from a prolonged screening interval and thereby reduce the burden of screening for HPV-vaccinated birth cohorts.

The study is deemed a method study by the ethical committee of the Capital region and informed consent is, therefore, not required. The study is approved by the Danish data protection agency.

The study will be undertaken as a method study embedded in the existing cervical screening program in the study area: Region Zealand, Northern Denmark region, Central Denmark region and part of region of Southern Denmark. The study is planned to run over three screening rounds. We expect 12000 women to be screened in the baseline screening round.

The study includes all women born in 1994 who live in the study area and participate in cervical screening. For a random half of these women, an HPV-DNA test is performed in addition to routine cervical cytology. The result of the HPV-test will not affect screening or follow-up, but is performed solely for purposes of the method study. CINtec p16 histology will be performed on all cervical biopsies in the study to ensure the quality of the diagnosis.

When screening samples are received at the pathology labs the allocation (HPV+/- in addition to cytology) will appear automatically in the IT-system.

The study will be conducted a non-inferiority study. If non-inferiority is declared, analysis for superiority will be conducted. Censoring will be performed in the event of death, emigration, end of study and at first cervical intraepithelial neoplasia grade 3 or above (CIN3+) or conization. Data on primary and secondary endpoints will be collected from National Health registers.

The project is supported by funds from 'Det Frie forskningsråd', 'Helsefonden' and 'Johannes Clemmesens Forskningsfond'. Cobas HPV-DNA and CINtec p16 histology test-kits are sponsored by Roche. Both tests were in standard use in the pathology departments prior to the project.

Results of the baseline screening round and final results from the study will be published in relevant peer-reviewed journals.

Study Type

Interventional

Enrollment (Anticipated)

7000

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
    • Copenhagen K
      • Copenhagen, Copenhagen K, Denmark, 1014
        • University of Copenhagen

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

23 years to 23 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women born in 1994 living in the study area

Exclusion Criteria:

  • None, as it is a public health trial

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

  • Primary Purpose: SCREENING
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: HPV-test
Cobas HPV-DNA test is performed on the cervical sample in addition to the routine cytology
Device: Cobas HPV-DNA test
Cobas HPV-DNA testing device from Roche is already in standard use in the Danish screening program for purpose of triage and primary screening of women 60+. It has four signals; HPV-negative, HPV-16, HPV-18 and "other"
NO_INTERVENTION: Routine
Screening with cytology as usual in the cervical screening program

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative CIN3+ (cervical intraepithelial neoplasia grade 3 and above) in baseline screen-negative women.
Time Frame: After up to 9 years follow-up (end-of-study)
Histologically proven CIN3+ is chosen as primary outcome measure because it is the diagnostic threshold above which conization is recommended by the Danish Society of Gynecology and Obstetrics. Primary outcome will be based on intention-to-treat and per protocol analysis and stratified by region of residence. Primary HPV-testing with cytology triage every six years compared to cytology every three years will be approximated from the observed data.
After up to 9 years follow-up (end-of-study)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative CIN3+ overall
Time Frame: After up to 9 years follow-up (end-of-study)
Intention-to-treat and per protocol analysis. Stratified by region of residence.
After up to 9 years follow-up (end-of-study)
Cumulative CIN2 (cervical intraepithelial neoplasia grade 2) overall
Time Frame: After up to 9 years follow-up (end-of-study)
Intention-to-treat and per protocol analysis. Stratified by region of residence.
After up to 9 years follow-up (end-of-study)
Cumulative CIN2 in baseline screen-negative women
Time Frame: After up to 9 years follow-up (end-of-study)
Intention-to-treat and per protocol analysis. Stratified by region of residence
After up to 9 years follow-up (end-of-study)
Cumulative CIN1 (cervical intraepithelial neoplasia grade 1) overall
Time Frame: After up to 9 years follow-up (end-of-study)
Intention-to-treat and per protocol analysis. Stratified by region of residence
After up to 9 years follow-up (end-of-study)
Cumulative CIN1 in baseline screen-negative women
Time Frame: After up to 9 years follow-up (end-of-study)
Intention-to-treat and per protocol analysis. Stratified by region of residence
After up to 9 years follow-up (end-of-study)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline CIN1
Time Frame: After up to 2 years follow-up
Number of women with the secondary outcome in the two study arms at baseline (baseline screening round).
After up to 2 years follow-up
Baseline CIN2
Time Frame: After up to 2 years follow-up
Number of women with the secondary outcome in the two study arms at baseline (baseline screening round).
After up to 2 years follow-up
Baseline CIN3+
Time Frame: After up to 2 years follow-up
Number of women with the secondary outcome in the two study arms at baseline (baseline screening round).
After up to 2 years follow-up
Baseline cytology (Bethesda classification)
Time Frame: After up to 2 years follow-up
Number of women with the secondary outcome in the two study arms at baseline (baseline screening round).
After up to 2 years follow-up
Baseline HPV-DNA status
Time Frame: After up to 2 years follow-up
Prevalence of HPV-infections; HPV-16, -18 and other
After up to 2 years follow-up
Baseline conization
Time Frame: After up to 2 years follow-up
Number of women with the secondary outcome in the two study arms after baseline screening.
After up to 2 years follow-up

Collaborators and Investigators

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

Sponsor

University of Copenhagen

Collaborators

Aalborg University Hospital
Naestved Hospital
Hospital of South West Jutland
Randers Regional Hospital
Soenderjylland Hospital

Investigators

  • Principal Investigator: Elsebeth Lynge, Professor, University of Copenhagen

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

Helpful Links

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)

February 1, 2017

Primary Completion (ANTICIPATED)

December 1, 2025

Study Completion (ANTICIPATED)

December 1, 2025

Study Registration Dates

First Submitted

January 31, 2017

First Submitted That Met QC Criteria

February 7, 2017

First Posted (ACTUAL)

February 10, 2017

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2022

Last Update Submitted That Met QC Criteria

November 3, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 102-2793/15-3000

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

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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