See and Treat in an Outpatient Setting in Women Above 45 Years With Cervical Dysplasia

The study will investigate if implementation of "see and treat" in the outpatient clinic can optimize the diagnosis, clinical follow-up and treatment of older women with positive cervical screening test.

Study Overview

• Status: Completed
• Conditions: Cervical Dysplasia; Cervical Lesion; Cervix Disease
• Intervention / Treatment: Procedure: Cone biopsy

Detailed Description

In Denmark, 370 women are diagnosed with cervical cancer every year and approximately 100 women die from the disease. Young women can be protected with the HPV vaccine, but it will take decades before the vaccine has an effect on older women. Women who are HPV positive have a risk of developing severe dysplasia of 25-55% within 10 years. Compared to younger women, older women are also more likely to be diagnosed with advanced-stage disease and their mortality is high. Due to retraction of the transformation zone into the cervical canal and atrophy of the mucosa the performance of colposcopy is low. Furthermore, the sensitivity of cytology decreases with age. This makes it very difficult to obtain sufficient biopsies and therefore postmenopausal women are often required to undergo colposcopy two to three times. Waiting for a final diagnosis and treatment not only has a large mental and practical impact on the women themselves, but it is also an economic burden for the health care system.

"See and treat" is a procedure that involves cervical cytology and HPV test, a colposcopy, cervical biopsies, and finally a loop electrosurgical excisional procedure by which the transformation zone is removed. This approach allows women to be diagnosed and treated in one visit.

In this project, the aim is to investigate if the implementation of "see and treat" in a gynecological outpatient clinic can optimize the diagnostics, clinical follow-up, and treatment of older women with abnormal cervical cytology or HPV-infection.

Participants Women aged ≥ 45 years with cervical dysplasia and/or a positive HPV test are referred from the general practitioner to the gynecological department.

Procedure At each inclusion site, the local project manager evaluates all the referred women for possible inclusion. Project information is sent either by e-mail or letter to eligible women. At the outpatient clinic, the eligible women will be informed about the project and asked to sign an informed consent form regarding their participation in the project.

If the eligible women agree to participate a physician in the outpatient clinic will obtain a cervical smear (i.e. cytology and Human Papillomavirus (HPV) test) and perform colposcopy and take four random biopsies. If the transformation zone (TZ) is partly visible or not visible a cone biopsy will be performed in local anesthesia (Citanest).

If the participant meet the exclusion criteria or declines to participate standard treatment will be offered (colposcopy and biopsies).

The included patients will be followed up with an HPV test after 6 months.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Jutland
    • Horsens, Jutland, Denmark, 8700
      • Horsens Regional Hospital
    • Randers, Jutland, Denmark, 8930
      • Randers Regional Hospital
    • Viborg, Jutland, Denmark, 8800
      • Viborg Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ≥ 45 years with a positive screening test (abnormal cytology and/or persistence HPV positive) who are referred to the Department of Obstetrics and Gynecology.
• Type 2 or 3 transformation zone (a partly or invisible transformation zone).

Exclusion Criteria:

• Type 1 transformation zone (fully visible)
• Current or previous diagnosis of cervical cancer.
• Pregnancy or pregnancy wish.
• Previously cone biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: See and treat; Cone biopsi is offered to women age ≥ 45 years referred to Department of Obstetrics and Gynecology due to a positive cervical screening test and partly or invisible transformation zone.	Procedure: Cone biopsy; Cone biopsy if transformation Zone (TZ) 2 or TZ 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cervical intraepithelial neoplasia ≥ grade 2 (CIN2+) lesion after referral with a positive cervical screening test	The prevalence of CIN2+ lesions in women ≥45 years included in the study	The histological diagnose from the Pathological Department will be available 8 weeks after inclusion.
Concordance between cytology and histology	Concordance between cytology, biopsies and cone biopsy in the ability to detect CIN2+ changes	The histological diagnose from the Pathological Department will be available 8 weeks after inclusion.
Clearance of HPV	Clearance rate of HPV after 6 months	This will be available 7 months after inclusion.
Complication rate	Complication rate of bleeding, infection and/or stenosis	Complication rate will be evaluated 6 months after inclusion.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Line W Gustafson, MD, Randers Regional Hospital and Aarhus University

Publications and helpful links

General Publications

• Hammer A, Gustafson LW, Christensen PN, Brondum R, Andersen B, Andersen RH, Tranberg M. Implementation of p16/Ki67 dual stain cytology in a Danish routine screening laboratory: Importance of adequate training and experience. Cancer Med. 2020 Nov;9(21):8235-8242. doi: 10.1002/cam4.3399. Epub 2020 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Colposcopy; Cone biopsy; See and treat
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Diseases; Precancerous Conditions; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Uterine Cervical Dysplasia; Uterine Cervical Diseases
• Other Study ID Numbers: 172230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The dataset generated and analyzed in this study are not available for the public due to Danish legislation.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No