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NCT03049553 Clinical Trial

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

Cervical Intraepithelial Neoplasia (CIN) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data
NCT number NCT03049553
Other study ID # 102-2793/15-3000
Secondary ID
Status Active, not recruiting
Phase N/A
First received
Last updated
Start date February 1, 2017
Est. completion date December 2025

Study information
Verified date November 2022
Source University of Copenhagen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Active, not recruiting
Enrollment 7000
Est. completion date December 2025
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender Female
Age group 23 Years to 23 Years
Eligibility Inclusion Criteria: - Women born in 1994 living in the study area Exclusion Criteria: - None, as it is a public health trial

Study Design

Related Conditions & MeSH terms

Intervention

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"

Locations
Country Name City State
Denmark University of Copenhagen Copenhagen Copenhagen K

Sponsors (6)
Lead Sponsor Collaborator
University of Copenhagen Aalborg University Hospital, Hospital of South West Jutland, Naestved Hospital, Randers Regional Hospital, Soenderjylland Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, de Sanjose S, Naucler P, Lloveras B, Kjaer S, Cuzick J, van Ballegooijen M, Clavel C, Iftner T; Joint European Cohort Study. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008 Oct 13;337:a1754. doi: 10.1136/bmj.a1754. — View Citation

Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, Berkhof J, Peto J, Meijer CJ; International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014 Feb 8;383(9916):524-32. doi: 10.1016/S0140-6736(13)62218-7. Epub 2013 Nov 3. Erratum in: Lancet. 2015 Oct 10;386(10002):1446. — View Citation

Outcome
Type Measure Description Time frame Safety issue
Other Baseline CIN1 Number of women with the secondary outcome in the two study arms at baseline (baseline screening round). After up to 2 years follow-up
Other Baseline CIN2 Number of women with the secondary outcome in the two study arms at baseline (baseline screening round). After up to 2 years follow-up
Other Baseline CIN3+ Number of women with the secondary outcome in the two study arms at baseline (baseline screening round). After up to 2 years follow-up
Other Baseline cytology (Bethesda classification) Number of women with the secondary outcome in the two study arms at baseline (baseline screening round). After up to 2 years follow-up
Other Baseline HPV-DNA status Prevalence of HPV-infections; HPV-16, -18 and other After up to 2 years follow-up
Other Baseline conization Number of women with the secondary outcome in the two study arms after baseline screening. After up to 2 years follow-up
Primary Cumulative CIN3+ (cervical intraepithelial neoplasia grade 3 and above) in baseline screen-negative women. 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 Cumulative CIN3+ overall Intention-to-treat and per protocol analysis. Stratified by region of residence. After up to 9 years follow-up (end-of-study)
Secondary Cumulative CIN2 (cervical intraepithelial neoplasia grade 2) overall Intention-to-treat and per protocol analysis. Stratified by region of residence. After up to 9 years follow-up (end-of-study)
Secondary Cumulative CIN2 in baseline screen-negative women Intention-to-treat and per protocol analysis. Stratified by region of residence After up to 9 years follow-up (end-of-study)
Secondary Cumulative CIN1 (cervical intraepithelial neoplasia grade 1) overall Intention-to-treat and per protocol analysis. Stratified by region of residence After up to 9 years follow-up (end-of-study)
Secondary Cumulative CIN1 in baseline screen-negative women Intention-to-treat and per protocol analysis. Stratified by region of residence After up to 9 years follow-up (end-of-study)

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