Predicting Treatment Failure in HSIL Patients with Positive Margins After Conization Via Detection of PAX1 Methylation

Multicenter Study on PAX1 Methylation for Predicting Lesion Persistence/Recurrence in HSIL Patients with Positive Margins After Cervical Conization

The goal of this multicenter, observational study is to evaluate whether methylation testing of paired box gene 1 (PAX1) can better predict and diagnose recurrence or persistent disease in patients with positive margins after cervical conization for high-grade squamous intraepithelial lesion (HSIL). The main question it aims to answer is:

Can PAX1 gene methylation testing provide a more accurate and effective prediction and diagnosis of cervical disease recurrence/persistence in addition to existing methods? Participants will be managed according to the latest clinical guidelines, and during follow-up, a non-invasive test, PAX1 gene methylation testing, will be added.

Study Overview

• Status: Not yet recruiting
• Conditions: High-grade Squamous Intraepithelial Lesions (HSIL); Cervical Conization

Detailed Description

This study is a multicenter, prospective observational study that qualitatively assesses the methylation status of the PAX1 gene in cervical exfoliated cells from patients with HSIL and positive margins after conization. The aim is to evaluate the ability of PAX1 gene methylation testing to predict treatment failure (lesion recurrence or persistence). The first follow-up occurs 6 months post-surgery, including high-risk human papillomavirus (hrHPV) testing and cytology, with referral for colposcopy, including biopsy and/or endocervical curettage (ECC), if necessary. Subsequent management and follow-up are based on examination results, following clinical guidelines, and arranged at intervals of 6-12 months depending on the findings. The follow-up includes routine clinical examinations widely applied in practice, and PAX1 testing will be completed at each follow-up visit. PAX1 testing, like hrHPV testing and cytology, will be performed using cervical exfoliated cells.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Lv Weiguo, Ph.D; Phone Number: 86-13588819218; Email: lbwg@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Women's Hospital School of Medicine Zhejiang University
      • Contact: Lv Weiguo; Phone Number: 0086-0571-87061501; Email: lbwg@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women undergoing their first cervical conization surgery for treatment or diagnosis at seven hospitals mentioned above in Zhejiang Province.

Description

Inclusion Criteria:

• Age greater than 25 years and less than 55 years;
• First-time cervical conization (cold knife conization or loop electrosurgical excision procedure);
• Postoperative pathology showing HSIL (CIN2 or CIN3);
• Positive margins for HSIL (CIN2 or CIN3) in conization specimen.

Exclusion Criteria:

• The presence of other malignant tumors or precancerous lesions;
• Lack of willingness for follow-up;
• Pregnant or breastfeeding women;
• Unable or unwilling to complete follow-up examinations;
• History of prior cervical disease treatment (surgical or physical therapy);
• Presence of immune system disorders.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the PAX1 methylation to detect treatment failure		2 years post-surgery
specificity of the PAX1 methylation to detect treatment failure		2 years post-surgery
Treatment failure rate within 24 months after surgery (cervical intraepithelial neoplasia grade 2+ (CIN2+) recurrence/residual rates)	the percentage of HSIL treatment failure (CIN2+ recurrence and residual) within 24 months after surgery	2 years post-surgery

Collaborators and Investigators

• Sponsor: Women's Hospital School Of Medicine Zhejiang University
• Collaborators: Huzhou Maternity and Child Care Hospital; Jiaxing Maternity and Child Health Care Hospital; Ningbo No. 1 Hospital; Jinhua Central Hospital; Shaoxing Maternity and Child Health Care Hospital; Taizhou Hospital Zhejiang Province

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: conization; cervical intraepithelial neoplasia; treatment failure; cervical cancer; positive margins; residual/recurrent disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Squamous Cell; Uterine Cervical Dysplasia; Precancerous Conditions; Uterine Cervical Diseases; Carcinoma, Squamous Cell; Squamous Intraepithelial Lesions of the Cervix; Carcinoma in Situ
• Other Study ID Numbers: IRB-20240248-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No