Clinical Triage and Treatment of Atypical Glandular Cells (AGC) Detected in Screening

April 4, 2023 updated by: Joakim Dillner, Karolinska Institutet

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

280

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

  • Sweden
      • Stockholm, Sweden
        • Karolinska University Hospital

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 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • give informed consent
  • Women diagnosed with AGC (atypical glandular cells, M69720) and HPV 16/18 positive, detected in cervical screening.

Exclusion Criteria:

  • Do not give informed consent
  • HPV negative or none-HPV16/18 positive

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Procedure: Conization
A cone biopsy to remove abnormal tissue.
Other Names:
  • Excision
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
Procedure: Colposcopy
  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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CIN3+
Time Frame: 2-3 years
Proportion of women with histologically verified HSIL+ (CIN3+) including AIS+ after AGC found in screening
2-3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CIN2+
Time Frame: 2-3 years
Proportion of women with histologically verified HSIL+ (CIN2+) including AIS+ after AGC found in screening
2-3 years

Collaborators and Investigators

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

Sponsor

Karolinska Institutet

Collaborators

Karolinska University Hospital
Regional Cancer Centre Stockholm Gotland

Investigators

  • Principal Investigator: Kristina Elfgren, MD, PhD, Karolinska University Hospital

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

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)

January 27, 2022

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2029

Study Registration Dates

First Submitted

January 29, 2022

First Submitted That Met QC Criteria

January 29, 2022

First Posted (Actual)

February 9, 2022

Study Record Updates

Last Update Posted (Actual)

April 5, 2023

Last Update Submitted That Met QC Criteria

April 4, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AGC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

To be determined.

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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