Uterine Cervical CancerNCT05231993
Clinical Triage and Treatment of Atypical Glandular Cells (AGC) Detected in Screening
A study testing Conization and Colposcopy in people with Uterine Cervical Cancer, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
The risk of cervical cancer after diagnosis with atypical glandular cells (AGC) detected by screening is elevated for 15 years after discovery. The current recommendation is that when AGC is detected during screening, referel is made to a gynecologist for colposcopy with biopsy within 3 months after the index test. Read more about this study
- Who is it for?
- Ages 23 to 64 years, women only
- Conditions the study is for
- Uterine Cervical Cancer
- What is being tested?
- Conization and Colposcopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 1 siteSweden
- Study dates
- 27 Jan 2022to Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 64 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- give informed consent
- Women diagnosed with AGC (atypical glandular cells, M69720) and HPV 16/18 positive, detected in cervical screening.
Who cannot join
- Do not give informed consent
- HPV negative or none-HPV16/18 positive
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Clinical Triage and Treatment of Atypical Glandular Cells (AGC) Detected in Screening: Randomized Healthservices Trial
The risk of cervical cancer after diagnosis with atypical glandular cells (AGC) detected by screening is elevated for 15 years after discovery. The current recommendation is that when AGC is detected during screening, referel is made to a gynecologist for colposcopy with biopsy within 3 months after the index test. Repeated tests should be done after one year and after two years and if these are negative, the woman can return to routine screening.
Given the increased risk of cancer associated with AGC a new evaluation of the optimal follow-up and treatment of AGC, which is detected during screening, is carried out. In this randomized study, women with AGC will be randomized to routine treatment according to current guidelines or to conization. The aim of the study is to determine which of the two treatments is most effective.
Read the detailed description
Evidence from a nationwide cohort study demonstrated that the risk of cervical cancer following a diagnosis of AGC detected in screening was elevated for 15 years, particularly the risk of adenocarcinoma. Furthermore, the study suggested that compared to high-grade squamous intraepithelial lesion (HSIL) management, the management of AGC has been suboptimal in Sweden (Wang et al., BMJ 2016). A study conducted in the greater metropolitan region of Stockholm showed that the PPV for high grade lesions was 60% for Human Papillomavirus (HPV) positive AGC detected in screening (Norman et al., BMJ Open, 2017).
The new guidelines for cervical cancer prevention were adopted in January of 2017 nationally and in December 2017 in county of Stockholm and outline a clinical management strategy for AGC. The recommendation is that AGC detected in screening, regardless of HPV status, should be referred to a gynecologist for colposcopy with biopsy within 3 months of the index test. For women over the age of 40, an ultrasound and endometrial biopsy is also recommended. Repeat tests should be done at one year and two years, if these are negative then the woman can return to routine screening.
The elevated risk for high grade lesions and cancer associated with AGC, coupled with the reality that cervical cancer incidence has increased in Sweden, begs a new evaluation of the optimal clinical management and treatment of AGC detected in screening. Women will be randomized to routine management according to the new guidelines or to an alternative management.
- Conditions
- Uterine Cervical Cancer
- Being tested
- Conization, Colposcopy
- Keywords
- cervical cancer, atypical glandular cells
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ConizationProcedure or surgery
Also called Excision
A cone biopsy to remove abnormal tissue.
ColposcopyProcedure or surgery
- Colposcopy with biopsy within 3 months,endocervical sample, ultrasound and endometrial biopsy if the woman is ≥40
- Colposcopy after 12 months if the first colposcopy and biopsies are normal
- Cytology and HPV testing at 12 and 24 months if the second colposcopy is normal
| Study group | Role | What they receive |
|---|---|---|
| Active comparator | Active comparator | 1. All women ages <41, women ages ≥41 with TZ1 and TZ2, and women ages ≥41 with a desire for further childbearing Clinical management and follow-up according to the national screening guidelines published in 2017 (same as for the comparator group, see below).
2. Women with TZ3 and women ages ≥41 with no desire for further childbearing a. Referral to (diagnostic) excision. The depth of the diagnostic excision will be clinically determined in the trial. It should be with the intent to treat but no so extensive that the risk for side effects increases.
The excision should include a cervical abrasion and endometrial sampling. Receives: Procedure: Conization |
| Placebo comparator | Placebo comparator | Clinical management and follow-up according to the national screening guidelines published in 2017:
1. Colposcopy with biopsy within 3 months, endocervical sample, ultrasound and endometrial biopsy if the woman is ≥40
2. Colposcopy after 12 months if the first colposcopy and biopsies are normal
3. Cytology and HPV testing at 12 and 24 months if the second colposcopy is normal Receives: Procedure: Colposcopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
CIN3+
Proportion of women with histologically verified HSIL+ (CIN3+) including AIS+ after AGC found in screening
Measured: 2-3 years
Secondary outcomes (1)
CIN2+
Proportion of women with histologically verified HSIL+ (CIN2+) including AIS+ after AGC found in screening
Measured: 2-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start27 Jan 2022
- Primary completionDec 2025 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Uterine Cervical CancerStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Regional Cancer Centre Stockholm Gotland, Karolinska University Hospital
- Responsible party
- Principal investigator, Joakim Dillner, Karolinska Institutet
- Investigators
- Kristina Elfgren, MD, PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231993
- Sponsor's protocol ID
- AGC
- Status last verified
- Mar 2025
- First submitted
- 29 Jan 2022
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: To be determined.
Publications
Norman I, Hjerpe A, Dillner J. Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study. BMJ Open. 2017 Dec 14;7(12):e017070. doi: 10.1136/bmjopen-2017-017070.
PubMed 29247086Wang J, Andrae B, Sundstrom K, Strom P, Ploner A, Elfstrom KM, Arnheim-Dahlstrom L, Dillner J, Sparen P. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ. 2016 Feb 11;352:i276. doi: 10.1136/bmj.i276.
PubMed 26869597
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Triage and Treatment of Atypical Glandular Cells (AGC) Detected in Screening: Randomized Healthservices Trial
- ClinicalTrials.gov ID
- NCT05231993
- Acronym / sponsor ID
- AGC
- Conditions
- Uterine Cervical Cancer
- Keywords
- cervical cancer, atypical glandular cells
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Regional Cancer Centre Stockholm Gotland, Karolinska University Hospital
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 9 Feb 2022 (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.
The risk of cervical cancer after diagnosis with atypical glandular cells (AGC) detected by screening is elevated for 15 years after discovery. The current recommendation is that when AGC is detected during screening, referel is made to a gynecologist for colposcopy with biopsy within 3 months after the index test. Repeated tests should be done after one year and after two years and if these are negative, the woman can return to routine screening.
Given the increased risk of cancer associated with AGC a new evaluation of the optimal follow-up and treatment of AGC, which is detected during screening, is carried out. In this randomized study, women with AGC will be randomized to routine treatment according to current guidelines or to conization. The aim of the study is to determine which of the two treatments is most effective.
Detailed description
Evidence from a nationwide cohort study demonstrated that the risk of cervical cancer following a diagnosis of AGC detected in screening was elevated for 15 years, particularly the risk of adenocarcinoma. Furthermore, the study suggested that compared to high-grade squamous intraepithelial lesion (HSIL) management, the management of AGC has been suboptimal in Sweden (Wang et al., BMJ 2016). A study conducted in the greater metropolitan region of Stockholm showed that the PPV for high grade lesions was 60% for Human Papillomavirus (HPV) positive AGC detected in screening (Norman et al., BMJ Open, 2017).
The new guidelines for cervical cancer prevention were adopted in January of 2017 nationally and in December 2017 in county of Stockholm and outline a clinical management strategy for AGC. The recommendation is that AGC detected in screening, regardless of HPV status, should be referred to a gynecologist for colposcopy with biopsy within 3 months of the index test. For women over the age of 40, an ultrasound and endometrial biopsy is also recommended. Repeat tests should be done at one year and two years, if these are negative then the woman can return to routine screening.
The elevated risk for high grade lesions and cancer associated with AGC, coupled with the reality that cervical cancer incidence has increased in Sweden, begs a new evaluation of the optimal clinical management and treatment of AGC detected in screening. Women will be randomized to routine management according to the new guidelines or to an alternative management.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active comparator | Active comparator | Procedure: Conization1. All women ages <41, women ages ≥41 with TZ1 and TZ2, and women ages ≥41 with a desire for further childbearing Clinical management and follow-up according to the national screening guidelines published in 2017 (same as for the comparator group, see below). 2. Women with TZ3 and women ages ≥41 with no desire for further childbearing a. Referral to (diagnostic) excision. The depth of the diagnostic excision will be clinically determined in the trial. It should be with the intent to treat but no so extensive that the risk for side effects increases. The excision should include a cervical abrasion and endometrial sampling. |
| Placebo comparator | Placebo comparator | Procedure: ColposcopyClinical management and follow-up according to the national screening guidelines published in 2017: 1. Colposcopy with biopsy within 3 months, endocervical sample, ultrasound and endometrial biopsy if the woman is ≥40 2. Colposcopy after 12 months if the first colposcopy and biopsies are normal 3. Cytology and HPV testing at 12 and 24 months if the second colposcopy is normal |
Who may qualify
- Ages
- 23 to 64 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- give informed consent
- Women diagnosed with AGC (atypical glandular cells, M69720) and HPV 16/18 positive, detected in cervical screening.
Key exclusion criteria (2 listed)
- Do not give informed consent
- HPV negative or none-HPV16/18 positive
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 |
|---|---|---|
| ConizationAlso: ExcisionA cone biopsy to remove abnormal tissue. | Procedure or surgery | Active comparator |
| Colposcopy1. Colposcopy with biopsy within 3 months,endocervical sample, ultrasound and endometrial biopsy if the woman is ≥40 2. Colposcopy after 12 months if the first colposcopy and biopsies are normal 3. Cytology and HPV testing at 12 and 24 months if the second colposcopy is normal | Procedure or surgery | Placebo comparator |
Primary outcome
CIN3+
Time frame: 2-3 years
Proportion of women with histologically verified HSIL+ (CIN3+) including AIS+ after AGC found in screening
1 secondary outcome
CIN2+
Time frame: 2-3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Results publication: PubMed 29247086Norman I, Hjerpe A, Dillner J. Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study. BMJ Open. 2017 Dec 14;7(12):e017070. doi: 10.1136/bmjopen-2017-017070.
- Results publication: PubMed 26869597Wang J, Andrae B, Sundstrom K, Strom P, Ploner A, Elfstrom KM, Arnheim-Dahlstrom L, Dillner J, Sparen P. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ. 2016 Feb 11;352:i276. doi: 10.1136/bmj.i276.
- Individual participant dataSharing planned: Yes. To be determined.
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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.
Kristina Elfgren, MD, PhD principal investigator
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conization and Colposcopy in people with Uterine Cervical Cancer, run by Karolinska Institutet at 1 site in Sweden.
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 2 inclusion and 2 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: enrolling by invitation, as of the sponsor's last update on 19 Mar 2025. 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 Sweden. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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?
CIN3+ (time frame: 2-3 years). 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 NCT05231993, which also lists 2 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 19 Mar 2025.