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

Karolinska Institute

Status: Invitation-only

Conditions: Uterine Cervical Cancer

Treatments: Procedure: Colposcopy; Procedure: Conization

Study type: Interventional

Funder types: Other

Identifiers

NCT05231993

AGC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 280 estimated patients

Sex: Female

Ages: 23 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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280 participants in 2 patient groups, including a placebo group

Active comparator

Active Comparator group

Description:

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.

Treatment:

Procedure: Conization

Placebo comparator

Placebo Comparator group

Description:

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

Treatment:

Procedure: Colposcopy