Preventing Invasive Cervical Cancer: The Importance of Expectant Management in Young Women With High-grade Pre-cancerous Lesions

Lesions classified as "High Grade Squamous Intra-epithelial Lesions" (HSIL) are pre-cervical lesions of the cervix, induced by infection with the Human Papilloma Virus (HPV). The detection and proper management of these lesions greatly reduces the incidence of invasive cervical cancer.

Pap smear remains the most effective tool for early detection of low and high-grade cervical lesions. In Belgium, screening for cervical cancer is recommended every 3 years for women between 25 and 65 years old.

HPV is a virus who possesses certain oncogenic genes who have the ability to inactivate tumor suppressor genes in the host cell. This promotes a tumorigenesis process within the tissues affected by the virus. The majority of human papillomavirus infections are transient and spontaneously cleared by host defense mechanisms, especially in the first two years after exposure. However, 10-20% of infections persist latently and may eventually lead to progression to invasive cervical cancer.

Even high-grade lesions kan naturally be cleared, even more so if the patient is young and immuno-competent. Therefore, the management of HSIL lesions in young women has been modified and consists of adopting mainly a conservative attitude, with controls every 6 months for 2 years. This management makes it possible to avoid unnecessary conizations of the cervix which, in young nulliparous patients, are not devoid of heavy obstetric consequences during subsequent pregnancies (premature birth, perinatal mortality). Cervical conization will only be considered for lesions that progress during follow-up or that persist beyond 2 years. However, this type of follow-up requires that patients be compliant.

Our study has two main objectives:

• to determine the compliance of CHU Brugmann Hospital patients who have been proposed a conservative strategy for the management of HSIL lesions.
• to identify the predictive factors for the persistence and / or progression of high-grade pre-cancerous dysplastic lesions.

Study Overview

• Status: Completed
• Conditions: High-Grade Squamous Intraepithelial Lesions
• Intervention / Treatment: Other: Data extraction from medical files; Biological: Immunohistochemistry

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Young women followed within the CHU Brugmann Hospital for HSIL lesions.

Description

Inclusion Criteria:

• Patients followed within the CHU Brugmann Hospital (no private practices).
• HSIL lesions confirmed by anatomopathologic analysis on cervical biopsies or cone specimen without evidence of invasive lesions

Exclusion Criteria:

• Invasive lesions

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Conservative management - progression; Young women with high grade pre-cancerous lesions, followed within the CHU Brugmann Hospital according to a conservative attitude, with progressive lesions or lesions remaining present after 2 years of follow-up.	Other: Data extraction from medical files; Data extraction from medical files; Biological: Immunohistochemistry; Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.
Conisation; Young women with high grade pre-cancerous lesions, followed within the CHU Brugmann Hospital by means of conisations.	Other: Data extraction from medical files; Data extraction from medical files; Biological: Immunohistochemistry; Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.
Conservative management - spontaneous regression; Young women with high grade pre-cancerous lesions, followed within the CHU Brugmann Hospital according to a conservative attitude, who showed a spontaneous regression of the lesions during the 2 years follow-up.	Other: Data extraction from medical files; Data extraction from medical files; Biological: Immunohistochemistry; Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient observance	Numeric value: 1 (optimal), 2 (acceptable), 3 (absent). Groups having benefited from a conservative attitude: Optimal compliance: 4 consultations in 24 months and / or indication of conization. Acceptable compliance: 2 to 3 consultations in 24 months. Observance absent: 0 to 1 consultation in 24 months. Groups having benefited from conization: Optimal compliance: 2 consultations after conisation. Acceptable compliance: 1 after consultation. Observance absent: 0 consultation after conisation.	Every six months over a period of 24 months
Cytologic results of the cervico-uterine smear.	Cytologic results of the cervico-uterine smear. Diagnose established by the anatomo-pathologist.	Every six months over a period of 24 months
Histologic results of the cervical biopsies	Histologic results of the cervical biopsies.Diagnose established by the anatomo-pathologist.	Every six months over a period of 24 months
Extent of dysplastic lesions	Defined as the number of quadrants reached by the lesion.	Every six months over a period of 24 months
Endocervix damage	Is the endocervix affected by the HSIL lesion (yes or no) ?	Every six months over a period of 24 months
Immuno-histologic results Ki67	Percentage of Ki67 antibody reactivity on the cervix biopsies	Every six months over a period of 24 months
Immuno-histologic results p16	Percentage of p16 antibody reactivity on the cervix biopsies	Every six months over a period of 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestity	Total number of pregnancies	Every six months over a period of 24 months
Parity	Total number of children born	Every six months over a period of 24 months
Age at first patient visit	Age at first patient visit	1 day
HIV status	HIV positive or negative	Every six months over a period of 24 months
Smoking status	Smoking or non smoking	Every six months over a period of 24 months
Response time to the convocation for colposcopy	Time between the patient's appointment and the receipt of the convocation for colposcopy	Up to 24 months
HPV status	Positive or negative for HPV virus	Every six months over a period of 24 months
Quality of colposcopic examinations	Defined as satisfactory or unsatisfactory (junction area completely seen or not seen).	Every six months over a period of 24 months

Collaborators and Investigators

• Sponsor: Catherine Vanpachterbeke
• Investigators: Principal Investigator: Georges Salem Wehbe, MD, CHU Brugmann

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): November 20, 2019

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Neoplasms, Squamous Cell; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Squamous Intraepithelial Lesions of the Cervix
• Other Study ID Numbers: CHUB-Salem Wehbe

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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