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

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ClinicalTrials.gov Identifier: NCT03049553
Recruitment Status : Active, not recruiting
First Posted : February 10, 2017
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
Naestved Hospital
Aalborg University Hospital
Soenderjylland Hospital
Sydvestjysk Hospital
Randers Regional Hospital
Information provided by (Responsible Party):
Elsebeth Lynges, University of Copenhagen

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cervical Intraepithelial Neoplasia (CIN) Device: Cobas HPV-DNA test Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Trial23 - A Method Study on the Use of Primary HPV-testing With Cytology Triage in Women Offered HPV-vaccination as Girls
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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


Other Outcome Measures:
  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. Baseline HPV-DNA status [ Time Frame: After up to 2 years follow-up ]
    Prevalence of HPV-infections; HPV-16, -18 and other

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   23 Years to 23 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women born in 1994 living in the study area

Exclusion Criteria:

  • None, as it is a public health trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03049553


Locations
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Denmark
University of Copenhagen
Copenhagen, Copenhagen K, Denmark, 1014
Sponsors and Collaborators
University of Copenhagen
Naestved Hospital
Aalborg University Hospital
Soenderjylland Hospital
Sydvestjysk Hospital
Randers Regional Hospital
Investigators
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Principal Investigator: Elsebeth Lynge, Professor University of Copenhagen
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Elsebeth Lynges, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT03049553    
Other Study ID Numbers: 102-2793/15-3000
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Elsebeth Lynges, University of Copenhagen:
Cervical screening
Human papillomavirus (HPV)
Cytology
HPV-test
Cervical intraepithelial neoplasia (CIN)
Additional relevant MeSH terms:
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Neoplasms
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type