Regression of Cervical Precancerous Lesions and Associated Risk Factors (RECER)

The aim of this study is to assess the extent of histopathological regression of severe cervical precancerous lesions (CIN 2 and CIN 3); evaluate the proportion of patients who experience the normalization of HPV test and cytology finding among those who were treated conservatively and those who underwent conization; and identify predictive parameters associated with regression. Based on this analysis, a model will be proposed to predict the likelihood of lesion regression.

Study Overview

• Status: Recruiting
• Conditions: HPV; CIN2; CIN3; Cervix Uteri SIL
• Intervention / Treatment: Diagnostic test: Colposcopy

Detailed Description

Introduction There are three grades of dysplasia of the cervix based on their severity (CIN 1-3). Most women with CIN 2 or CIN 3 (high-grade - HG lesions) are referred for conization due to the presumed risk of developing invasive cervical cancer. However, this surgical intervention is associated with an increased risk of preterm labor in the future.

From the literature, it is evident that 30% - 60% of CIN 2 and CIN 3 lesions spontaneously regress. Colposcopic examination is a tool that can accurately assess the severity of the lesion and safely evaluate the dynamics of its development. It can be used to exclude the presence of invasive cervical cancer.

The aim of the study is to determine the absolute rate of spontaneous regression of HG lesions, considering stratification factors.

Methods Patients meeting all inclusion criteria and none of the exclusion criteria are included (see below). Colposcopic evaluations occur at four-month intervals during the study. In case of progression, the patient is indicated for conization; in case of persistence, the patient is consulted and can choose further observation or conization; in case of regression, punch biopsy is performed to acquire a histopathologic sample for primary endpoint evaluation. The biopsy/conization result is subsequently compared with the initial sample to declare regression or persistence of the HG lesion.

The HPV status and cytological findings are evaluated similarly. Stratification criteria such as age, colposcopic characteristics, HPV genotype (Cobas 4800, Roche Molecular Systems, Pleasanton, USA), methylation markers (GynTect®, Oncgnostics GmbH, Löbstedter Str. 41, 07749 Jena, Germany), semiquantitative microscopic assessment of the vaginal swab, and personal history are assessed during monitoring.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Lukas Dostalek; Phone Number: +420224967451; Email: lukas.dostalek@vfn.cz

Study Locations

• Czechia
  • Prague, Czechia, 12800
    • Recruiting
    • General University Hospital
    • Contact: Lukas Dostalek; Phone Number: +420224967451; Email: lukas.dostalek@vfn.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Consecutive participant sampling of patients with bioptically-verified CIN 2 or CIN 3 and fully visualised squamocolumnar junction with no suspiction on invasive cancer or glandular lesion.

Description

Inclusion Criteria:

1. squamocolumnar junction fully visualized
2. bioptically verified CIN 2 or CIN 3
3. age ≥ 18 years
4. age ≤ 40 years
5. informed consent

Exclusion Criteria:

1. squamocolumnar junction not fully visualized
2. suspicion on glandular lesion
3. suspicion on invasive cancer
4. personal history of CIN 2, 3 or cerv. cancer
5. gravidity
6. HIV positivity
7. immunosuppression
8. impossible photographic documentation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CIN 2, CIN 3; Bioptically verified CIN 2 or CIN 3 lesion	Diagnostic test: Colposcopy; No surgery, observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regression-rate of severe cervical precancerous lesions (CIN 2 and CIN 3) expressed through a comparison of initial and final histology	Histological results from the initial visit will be compared with the biopsy obtained during the last visit (or the specimen from conization) to determine whether regression or persistence of the high-grade lesion has occurred.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of HPV negativization in patients with spontaneous regression compared to patients with persistence after conization	The proportion of patients with a negative result on the HPV DNA test obtained during the final visit will be assessed.	3 years
Rate of cytological normalization in patients with spontaneous regression compared to patients with persistence after conization		3 years
Regression-rate considering specified stratification factors	Specific factors will be evaluated to determine their influence on the regression or persistence of the cervical high-grade lesion. The following factors will be assessed: CIN Grade (CIN 2 / CIN 3); Immunohistochemically detected biomarkers; p16INK4a; Ki-67; E4; Gene methylation (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671); Histologically described cervicitis; Colposcopic Markers; Microbiological Markers; Selective HPV genotyping; Viral load; Anamnestic Data; Smoking; Age	3 years
Development of a model for predicting spontaneous regression		3 years

Collaborators and Investigators

• Sponsor: General University Hospital, Prague

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 24, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Uterine Cervical Dysplasia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Squamous Intraepithelial Lesions of the Cervix
• Other Study ID Numbers: 154/22 S

Drug and device information, study documents

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