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

Study Overview
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Brief Summary
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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.

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

Conditions
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High-Grade Squamous Intraepithelial Lesions

Intervention / Treatment
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* Other: Data extraction from medical files
* Biological: Immunohistochemistry


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Conservative management - progression<br>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<br>* Data extraction from medical files<br>Biological: Immunohistochemistry<br>* Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.<br>|
| Conisation<br>Young women with high grade pre-cancerous lesions, followed within the CHU Brugmann Hospital by means of conisations. | Other: Data extraction from medical files<br>* Data extraction from medical files<br>Biological: Immunohistochemistry<br>* Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.<br>|
| Conservative management - spontaneous regression<br>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<br>* Data extraction from medical files<br>Biological: Immunohistochemistry<br>* Immunohistochemistry with Ki67 and p16 antibodies on residual samples, if this had not been foreseen in the standard of care management of the patient.<br>|

What is the study measuring?
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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 |