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

NCT ID: NCT05231993

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-27
• Study Completion Date: 2029-12-31

Brief 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. 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.

Conditions

Uterine Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Conization

Intervention Type: PROCEDURE

A cone biopsy to remove abnormal tissue.

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

Group Type: PLACEBO_COMPARATOR

Colposcopy

Intervention Type: PROCEDURE

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

Interventions

Conization

A cone biopsy to remove abnormal tissue.

Intervention Type: 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

Intervention Type: PROCEDURE

Other Intervention Names

Excision

Eligibility Criteria

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

• Minimum Eligible Age: 23 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Regional Cancer Centre Stockholm Gotland

OTHER

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Joakim Dillner

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kristina Elfgren, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Karolinska University Hospital

Stockholm, , Sweden

Countries

Sweden

References

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.

Reference Type: RESULT

PMID: 29247086 (View on PubMed)

Wang 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.

Reference Type: RESULT

PMID: 26869597 (View on PubMed)

Other Identifiers

AGC

Identifier Type: -

Identifier Source: org_study_id