Cervical Intraepithelial Neoplasia (CIN)NCT03049553
Trial23 - A Method Study on Cervical Screening in Women Offered HPV-vaccination as Girls
A study testing Cobas HPV-DNA test in people with Cervical Intraepithelial Neoplasia (CIN), run by University of Copenhagen at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 23 to 23 years, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia (CIN)
- What is being tested?
- Cobas HPV-DNA test
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7,000 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2017to Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 23 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women born in 1994 living in the study area
Who cannot join
- None, as it is a public health trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Cervical Intraepithelial Neoplasia (CIN)
- Being tested
- Cobas HPV-DNA test
- Keywords
- Cervical screening, Human papillomavirus (HPV), Cytology, HPV-test, Cervical intraepithelial neoplasia (CIN)
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cobas HPV-DNA testDevice
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"
| Study group | Role | What they receive |
|---|---|---|
| HPV-test | Other | Cobas HPV-DNA test is performed on the cervical sample in addition to the routine cytology Receives: Device: Cobas HPV-DNA test |
| Routine | No intervention | Screening with cytology as usual in the cervical screening program |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After up to 9 years follow-up (end-of-study)
Secondary outcomes (5)
Cumulative CIN3+ overall
Intention-to-treat and per protocol analysis. Stratified by region of residence.
Measured: After up to 9 years follow-up (end-of-study)
Cumulative CIN2 (cervical intraepithelial neoplasia grade 2) overall
Intention-to-treat and per protocol analysis. Stratified by region of residence.
Measured: After up to 9 years follow-up (end-of-study)
Cumulative CIN2 in baseline screen-negative women
Intention-to-treat and per protocol analysis. Stratified by region of residence
Measured: After up to 9 years follow-up (end-of-study)
Cumulative CIN1 (cervical intraepithelial neoplasia grade 1) overall
Intention-to-treat and per protocol analysis. Stratified by region of residence
Measured: After up to 9 years follow-up (end-of-study)
Cumulative CIN1 in baseline screen-negative women
Intention-to-treat and per protocol analysis. Stratified by region of residence
Measured: After up to 9 years follow-up (end-of-study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2017
- Study start1 Feb 2017
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cervical Intraepithelial Neoplasia (CIN)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Naestved Hospital, Aalborg University Hospital, Soenderjylland Hospital, Esbjerg Hospital - University Hospital of Southern Denmark, Randers Regional Hospital
- Responsible party
- Principal investigator, Elsebeth Lynges, University of Copenhagen
- Investigators
- Elsebeth Lynge, Professor, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03049553
- Sponsor's protocol ID
- 102-2793/15-3000
- Status last verified
- Nov 2022
- First submitted
- 31 Jan 2017
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ronco G, Dillner J, Elfstrom 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.
PubMed 24192252Dillner 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.
PubMed 18852164Thamsborg LH, Andersen B, Larsen LG, Christensen J, Johansen T, Hariri J, Christiansen S, Rygaard C, Lynge E. Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol. BMJ Open. 2018 May 26;8(5):e020294. doi: 10.1136/bmjopen-2017-020294.
PubMed 29804060
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial23 - A Method Study on the Use of Primary HPV-testing With Cytology Triage in Women Offered HPV-vaccination as Girls
- ClinicalTrials.gov ID
- NCT03049553
- Acronym / sponsor ID
- 102-2793/15-3000
- Conditions
- Cervical Intraepithelial Neoplasia (CIN)
- Keywords
- Cervical screening, Human papillomavirus (HPV), Cytology, HPV-test, Cervical intraepithelial neoplasia (CIN)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 7,000 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Naestved Hospital, Aalborg University Hospital, Soenderjylland Hospital, Esbjerg Hospital - University Hospital of Southern Denmark, Randers Regional Hospital
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 10 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HPV-test | Other | Device: Cobas HPV-DNA testCobas HPV-DNA test is performed on the cervical sample in addition to the routine cytology |
| Routine | No intervention | –Screening with cytology as usual in the cervical screening program |
Who may qualify
- Ages
- 23 to 23 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Women born in 1994 living in the study area
Key exclusion criteria (1 listed)
- None, as it is a public health trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cobas HPV-DNA testCobas 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" | Device | HPV-test |
Primary outcome
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.
5 secondary outcomes
Cumulative CIN3+ overall
Time frame: 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)
Cumulative CIN2 in baseline screen-negative women
Time frame: 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)
Cumulative CIN1 in baseline screen-negative women
Time frame: After up to 9 years follow-up (end-of-study)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Background: PubMed 24192252Ronco G, Dillner J, Elfstrom 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.
- Background: PubMed 18852164Dillner 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.
- Derived from this study: PubMed 29804060Thamsborg LH, Andersen B, Larsen LG, Christensen J, Johansen T, Hariri J, Christiansen S, Rygaard C, Lynge E. Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol. BMJ Open. 2018 May 26;8(5):e020294. doi: 10.1136/bmjopen-2017-020294.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elsebeth Lynge, Professor principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cobas HPV-DNA test in people with Cervical Intraepithelial Neoplasia (CIN), run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03049553, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.