Conservative Management of CIN2 Lesions and Biomarkers Evaluation

NCT ID: NCT04687267

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 319 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-15
• Study Completion Date: 2022-12-31

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.

Detailed Description

Women aged 25-45 years, adherent to the organized population-based cervical screening program, with a histological diagnosis of CIN2 and fulfilling the inclusion criteria will be invited to participate to the study, previously providing specific information; in case of acceptance, informed consent is signed.

STUDY PROTOCOL:

The adherent women will attend periodical control visits:

• every 6 months up to 24 months, with performance of: pap test (PT) and colposcopy (with biopsy in case of visible alterations);
• at 6 and 12 months control visit: a liquid-based sample of cervical cells will be collected for the biomarkers' analyses.

BIOMARKERS:

1. - HPV search and partial HPV16/18 genotyping, by cobas 4800 high-risk HPV assay (Roche); PCR with MY09/MY11 consensus primers and full genotyping by restriction fragment length analysis, plus PCR with beta-globin primers (in-house);

2. - methylation analysis of the cellular genes FAM194A and hsa-mir124-2, by methylation-specific quantitative PCR test (qMSP - QIAsure methylation test, Qiagen);

3. - methylation analysis of the L1 and L2 viral genes of HPV types 16 and 18, by pyrosequencing;

4. - immunocytochemical analysis for p16INK4A/Ki67 proteins (dual stain), by p16INK4A/Ki67 immunocytochemical analysis by CINtec Plus kit (Roche).

Conditions

CIN2

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Azienda ULSS 3 Serenissima

OTHER

Sponsor Role: collaborator

Azienda Ulss 6 Euganea

OTHER

Sponsor Role: collaborator

Azienda Ulss 2 Marca Trevigiana

OTHER

Sponsor Role: collaborator

Azienda Ulss 9 Scaligera

OTHER_GOV

Sponsor Role: collaborator

Regione Veneto

OTHER

Sponsor Role: collaborator

Istituto Oncologico Veneto IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Annarosa Del Mistro

Head of HPV laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tiziano Maggino, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda ULSS 3 Serenissima

Locations

Azienda ULSS 6 Euganea

Padua, PD, Italy

Azienda ULSS 2 Marca Trevigiana

Treviso, TV, Italy

Azienda ULSS 3 Serenissima

Mestre, VE, Italy

Azienda ULSS 9 Scaligera

Verona, VR, Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 26180819 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28263992 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24757722 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29579066 (View on PubMed)

Other Identifiers

CIN2-RSFR

Identifier Type: -

Identifier Source: org_study_id