Conservative Management of CIN2 Lesions and Biomarkers Evaluation

NCT04687267 | Completed

• 1 other identifier: CIN2-RSFR
• Study Type: observational
• Target: 319
• Locations: 1 country
• Sites: 4

Brief Summary

Prospective study including women aged 25-45 years, adherent to the cervical screening program of four different centers of the Veneto region, with a diagnosis of CIN2 lesion. After enrollment according to predefined criteria, and informed consent to participate, the CIN2 lesions are managed by follow-up; cases with progressive lesions will be treated immediately, cases with CIN2 persistence for more than 12 months will be treated as well. Viral, molecular and immunocytochemical biomarkers will be studied, and evaluated in relation to the clinical outcome.

Conditions

CIN2

Keywords

biomarkers; HPV; methylation; clinical outcome

Outcome Measures

Primary Outcomes (4)

• Rate of spontaneous regression of CIN2 lesions

  Eligible women will not be treated at diagnosis, but periodically followed-up. Treatment will be provided for progressive lesions and lesions persisting more than 12 months. The rates of lesion regression will be calculated: number of lesions regressed to CIN1 or normal / total number of cases.

  Through study completion, an average of 2 years.

• CIN2 clinical outcome by HPV genotype

  Rate of CIN2 regression will be calculated in relation to positivity for HPV16 vs positivity for other high-risk types (number of regressed HPV16-related CIN2 lesions / total number of HPV16-related CIN2 vs number of regressed non-HPV16-related CIN2 lesions / total number of non-HPV16-related CIN2 lesions).

  Through study completion, an average of 2 years.

• CIN2 clinical outcome by DNA methylation

  Rate of CIN2 regression will be calculated in relation to DNA methylation of cellular and viral genes (number of regressed hypermethylated CIN2 lesions / total number of CIN2 lesions with valid result for each gene analyzed).

  Through study completion, an average of 2 years.

• CIN2 clinical outcome by p16/ki67 protein expression

  Rate of CIN2 regression will be calculated in relation to positivity for p16/ki67 expression (number of regressed p16/ki67-positive CIN2 lesions / total number of CIN2 lesions with valid result for p16/ki67 expression).

  Through study completion, an average of 2 years.

Secondary Outcomes (1)

• Adhesion to CIN2 conservative management.

  2 years

Eligibility Criteria

• Age: 25 Years - 45 Years
• Gender Eligibility Details: The study is related to a disease of the female genital tract.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Women attending organized population-based cervical cancer screening with a histological CIN2 lesion, meeting the selection criteria and consenting to participate.

You may qualify if:

• age range 25-45 years,
• CIN2 lesions located in the exocervix and completely visible at colposcopy.

You may not qualify if:

• age \>45 years;
• history of previous high-grade lesions;
• squamo-columnar junction not completely visible (type 3);
• cytology with suspect or indicative for invasive lesion;
• lesions exclusively located in the endocervix;
• lesions located in the exocervix but not completely visible;
• pregnancy

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• Azienda ULSS 3 Serenissima: collaborator
• Azienda Ulss 6 Euganea: collaborator
• Azienda Ulss 2 Marca Trevigiana: collaborator
• Azienda Ulss 9 Scaligera: collaborator
• Regione Veneto: collaborator

Study Sites (4)

Azienda ULSS 6 Euganea

Padua, PD, Italy

Location

Azienda ULSS 2 Marca Trevigiana

Treviso, TV, Italy

Location

Azienda ULSS 3 Serenissima

Mestre, VE, Italy

Location

Azienda ULSS 9 Scaligera

Verona, VR, Italy

Location

Related Publications (4)

• Del Mistro A, Matteucci M, Insacco EA, Onnis G, Da Re F, Baboci L, Zorzi M, Minucci D. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study. Biomed Res Int. 2015;2015:984528. doi: 10.1155/2015/984528. Epub 2015 Jun 9.

  PMID: 26180819 BACKGROUND

• Del Mistro A, Frayle H, Rizzi M, Fantin G, Ferro A, Angeletti PM, Giorgi Rossi P, Altobelli E. Methylation analysis and HPV genotyping of self-collected cervical samples from women not responding to screening invitation and review of the literature. PLoS One. 2017 Mar 6;12(3):e0172226. doi: 10.1371/journal.pone.0172226. eCollection 2017.

  PMID: 28263992 BACKGROUND

• Ordi J, Sagasta A, Munmany M, Rodriguez-Carunchio L, Torne A, del Pino M. Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathol. 2014 Mar;122(3):227-35. doi: 10.1002/cncy.21366.

  PMID: 24757722 BACKGROUND

• Gillio-Tos A, Fiano V, Grasso C, Trevisan M, Gori S, Mongia A, De Marco L, Ronco G; New Technologies for Cervical Cancer Screening (NTCC) Working Group. Assessment of viral methylation levels for high risk HPV types by newly designed consensus primers PCR and pyrosequencing. PLoS One. 2018 Mar 26;13(3):e0194619. doi: 10.1371/journal.pone.0194619. eCollection 2018.

  PMID: 29579066 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Cervical cells and DNA extracted therefrom to be used for biomarkers analyses, retained for the duration of the study.

Study Officials

• Tiziano Maggino, MD

  Azienda ULSS 3 Serenissima

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of HPV laboratory

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 29, 2020
• Study Start: April 15, 2019
• Primary Completion: October 31, 2021
• Study Completion: December 31, 2022
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

IT (4)