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

Uterine Cervical Cancer Clinical Trial

Official title:

Clinical Triage and Treatment of Atypical Glandular Cells (AGC) Detected in Screening: Randomized Healthservices Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05231993
• Other study ID #: AGC
• Status: Enrolling by invitation
• Phase: N/A
• Start date: January 27, 2022
• Est. completion date: December 2029

Study information

• Verified date: April 2023
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 280
• Est. completion date: December 2029
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 23 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Uterine Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Procedure:
• Conization
A cone biopsy to remove abnormal tissue.
• Colposcopy
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

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska Institutet	Karolinska University Hospital, Regional Cancer Centre Stockholm Gotland

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

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. — View Citation

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: 10.113 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CIN3+	Proportion of women with histologically verified HSIL+ (CIN3+) including AIS+ after AGC found in screening	2-3 years
Secondary	CIN2+	Proportion of women with histologically verified HSIL+ (CIN2+) including AIS+ after AGC found in screening	2-3 years