Evaluation of the PreCursor-M+® in CIN2

Evaluation of the PreCursor-M+® Assay Performance in the Management of Women Diagnosed With CIN2

The goal of this observational study is to to evaluate the accuracy and sensitivity of PreCursor-M+ on a post-aliquot of liquid-based cytology (LBC) cervical samples (biopsy) obtained by physicians in a group of women with histologically-proven diagnoses of CIN2.

The PreCursor-M+® assay is a multiplex real-time methylation specific PCR test that identifies the level of promotor methylation of the host cell genes FAM19A4 and miR124-2, known biomarkers associated with cervical carcinoma and transforming CIN in cervical cells.

To evaluate the clinical course of CIN2 at 2 years after the first diagnosis, with an interval evaluation at 6 months.

After enrolment, women will be divided into two groups: "active surveillance" and "immediate treatment". In the first group, clinical outcomes to be assessed, in relation to the PreCursor-M+ result at baseline, will include regression to <CIN2, persistence of CIN2, and progression to CIN3+. In the second group, we will evaluate the histological diagnosis at cone specimen (downgrading or upgrading) and the 2-year cumulative incidence of CIN2+ recurrence based on the PreCursor-M+ result at baseline.

Study Overview

• Status: Recruiting
• Conditions: Cervical Intraepithelial Neoplasia Grade 2

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

Contacts and Locations

• Study Contact: Name: ANNA DANIELA IACOBONE; Phone Number: +39 0294371088; Email: annadaniela.iacobone@ieo.it

Study Locations

• Italy
  • Milan, Italy
    • Not yet recruiting
    • European Institute of Oncology
    • Contact: Anna Daniela Iacobone
  • Milan, Italy, 20141
    • Recruiting
    • European Institute of Oncology, Milan,
    • Contact: ANNA DANIELA IACOBONE; Phone Number: +39 0294371088; Email: annadaniela.iacobone@ieo.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

women with histological diagnosis of CIN2

Description

Inclusion Criteria:

1. age at diagnosis of 18 years or older;
2. histological confirmation of CIN2 after colposcopic-guided cervical biopsy or conservative surgical treatment, including loop electrosurgical excision procedure (LEEP) and laser conization;
3. known HPV test result at baseline;
4. ability to understand and sign the informed consent;
5. written informed consent given.

Exclusion criteria:

1. unknown HPV test result at diagnosis;
2. vulnerable patients.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
active surveillance; wait-and-see strategy
immediate treatment; surgical treatment per clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of methylation of the host cell genes FAM19A4 and miR124-2	The PreCursor-M+® assay is a multiplex real-time methylation specific PCR test that identifies the level of promotor methylation of the host cell genes FAM19A4 and miR124-2, known biomarkers associated with cervical carcinoma and transforming CIN in cervical cells. This test can identify patients with spontaneous regressing precancer lesions (negative result) from patients with a progressing precancer lesion (positive result).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of clinical course of CIN2 at 2 years after diagnosis	To evaluate the clinical course of CIN2 at 2 years after the first diagnosis, with an interval evaluation at 6 months. After enrolment, women will be divided into two groups: "active surveillance" and "immediate treatment". In the first group, clinical outcomes to be assessed, in relation to the PreCursor-M+ result at baseline, will include regression to <CIN2, persistence of CIN2, and progression to CIN3+. In the second group, we will evaluate the histological diagnosis at cone specimen (downgrading or upgrading) and the 2-year cumulative incidence of CIN2+ recurrence based on the PreCursor-M+ result at baseline.	2 years
Evaluation of overall accuracy of PreCursor-M+	Overall accuracy, positive predictive value and negative predictive value of PreCursor-M+	6 months - 2 years

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Anna Daniela Iacobone, European Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2024
• Primary Completion (Estimated): June 17, 2025
• Study Completion (Estimated): June 17, 2027

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Precancerous Conditions; Uterine Cervical Diseases; Uterine Cervical Dysplasia
• Other Study ID Numbers: UID 4438

Drug and device information, study documents

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