Role of Methylation Test Triage in HPV Positive Women

NCT06366516 | Not Yet Recruiting

• 1 other identifier: FUOBGY2024-23
• Study Type: interventional
• Target: 10,000
• Locations: 1 country
• Sites: 1

Brief Summary

The pathological results were used as the gold standard in this study and the investigators analyze the diagnostic value of six gene methylation status (ASTN1 DLX1, ITGA4, RXFP3, SOX17, ZNF671) in triaging high-risk human papillomavirus infection. The sensitivity and specificity of methylation test and cytology in the diagnosis of high-grade cervical lesions are compared in order to providing new methods and basis in improving the accuracy of cervical cancer screening.

Conditions

Precancerous Cervical Lesion

Keywords

Human papillomavirus; High-grade squamous intraepithelial lesion; Methylation; Cervical cancer screening; Triage; Adenocarcinoma in Situ; Cytology

Outcome Measures

Primary Outcomes (1)

• The sensitivity and specificity of methylation test in detecting CIN2+.

  The primary variable of methylation test are as follows:clinical sensitivity, clinical specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, positive coincidence rate, and negative coincidence rate.

  From date of enrollment until the date of first documented CIN2+,assessed up to 12 months

Secondary Outcomes (1)

• KAPPA value of methylation test.

  From date of enrollment until the date of first documented CIN2+,assessed up to 12 months

Study Arms (1)

Women aged 25-65 years with high-risk HPV infection.

EXPERIMENTAL

Ten thousand women were recruited who aged 25-65 years and they are positive for high-risk HPV.

Diagnostic Test: Methylation Test

Interventions

Methylation Test DIAGNOSTIC_TEST

Participants who aged 25-65 years with high-risk HPV infection are recruited.To start with,cervical exfoliated cells are collected, coded (according to the actual enrollment sequence), and stored in the pathology department where methylation testing is performed.In addition,patients will underwent colposcopy and biopsy. Patients are followed up by cytology, high-risk HPV and methylation tests at 6 and 12 months after enrollment.Cervical conization and hysterectomy will be taken if necessary according to histopathological results. The clinical endpoint is reached when CIN2+ is confirmed by histopathological result.

Also known as: Liquid-based Cytology Test, High-risk HPV test, Colposcopy, Biopsy

Women aged 25-65 years with high-risk HPV infection.

Eligibility Criteria

• Age: 25 Years - 65 Years
• Gender Eligibility Details: The aim of this study is to evaluate the value of methylation test in high-risk HPV positive women who aged 25 to 65 years for detecting high-grade cervical lesions and cervical cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 25\~65 years undergoing cervical cancer screening
• normal for cytology and positive for hrHPV
• informed consent was obtained

You may not qualify if:

• pregnant
• with a known history of ablation or treatment with cervical excision within 12 months
• hysterectomy
• chemoradiotherapy
• planning to participate or taking part in another cancer screening, treatment, or vaccination study
• give up the trial or naturally dropped out of the follow-up during the observation process
• people who asked to withdraw

Sponsors & Collaborators

• Obstetrics & Gynecology Hospital of Fudan University: lead
• Peking Union Medical College Hospital: collaborator
• Chengdu Women's and Children's Central Hospital: collaborator
• Guangdong Women and Children Hospital: collaborator
• Second Hospital of Jilin University: collaborator
• First Affiliated Hospital of Xinjiang Medical University: collaborator
• Third Affiliated Hospital of Zhengzhou University: collaborator

Study Sites (1)

Obstetrics and Gynecology Hospital of Fudan University

Shanghai, Shanghai Municipality, 200011, China

Location

Related Publications (8)

• Kremer WW, Steenbergen R, Heideman D, Kenter GG, Meijer C. The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review. BJOG. 2021 Feb;128(3):504-514. doi: 10.1111/1471-0528.16395. Epub 2020 Aug 9.

  PMID: 32619334 BACKGROUND

• Giorgi Rossi P, Carozzi F, Ronco G, Allia E, Bisanzi S, Gillio-Tos A, De Marco L, Rizzolo R, Gustinucci D, Del Mistro A, Frayle H, Confortini M, Iossa A, Cesarini E, Bulletti S, Passamonti B, Gori S, Toniolo L, Barca A, Bonvicini L, Mancuso P, Venturelli F, Benevolo M; the New Technology for Cervical Cancer 2 Working Group. p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women. J Natl Cancer Inst. 2021 Mar 1;113(3):292-300. doi: 10.1093/jnci/djaa105.

  PMID: 32745170 RESULT

• van den Helder R, Steenbergen RDM, van Splunter AP, Mom CH, Tjiong MY, Martin I, Rosier-van Dunne FMF, van der Avoort IAM, Bleeker MCG, van Trommel NE. HPV and DNA Methylation Testing in Urine for Cervical Intraepithelial Neoplasia and Cervical Cancer Detection. Clin Cancer Res. 2022 May 13;28(10):2061-2068. doi: 10.1158/1078-0432.CCR-21-3710.

  PMID: 35266975 RESULT

• Dovnik A, Poljak M. The Role of Methylation of Host and/or Human Papillomavirus (HPV) DNA in Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) Lesions. Int J Mol Sci. 2023 Mar 30;24(7):6479. doi: 10.3390/ijms24076479.

  PMID: 37047452 RESULT

• Mazurec K, Trzeszcz M, Mazurec M, Streb J, Halon A, Jach R. Triage Strategies for Non-16/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16/Ki67 Dual Stain vs. Cytology. Cancers (Basel). 2023 Oct 21;15(20):5095. doi: 10.3390/cancers15205095.

  PMID: 37894462 RESULT

• Yang S, Wu Y, Wang S, Xu P, Deng Y, Wang M, Liu K, Tian T, Zhu Y, Li N, Zhou L, Dai Z, Kang H. HPV-related methylation-based reclassification and risk stratification of cervical cancer. Mol Oncol. 2020 Sep;14(9):2124-2141. doi: 10.1002/1878-0261.12709. Epub 2020 Jun 2.

  PMID: 32408396 RESULT

• Stoler MH, Baker E, Boyle S, Aslam S, Ridder R, Huh WK, Wright TC Jr. Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki-67 dual-stained cytology-Retrospective insights from ATHENA. Int J Cancer. 2020 May 1;146(9):2599-2607. doi: 10.1002/ijc.32669. Epub 2019 Oct 6.

  PMID: 31490545 RESULT

• Wright TC Jr, Stoler MH, Ranger-Moore J, Fang Q, Volkir P, Safaeian M, Ridder R. Clinical validation of p16/Ki-67 dual-stained cytology triage of HPV-positive women: Results from the IMPACT trial. Int J Cancer. 2022 Feb 1;150(3):461-471. doi: 10.1002/ijc.33812. Epub 2021 Sep 25.

  PMID: 34536311 RESULT

MeSH Terms

Conditions

Squamous Intraepithelial Lesions; Adenocarcinoma in Situ

Interventions

Colposcopy; Biopsy

Condition Hierarchy (Ancestors)

Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Obstetrical and Gynecological; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Obstetric Surgical Procedures; Gynecologic Surgical Procedures; Urogenital Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Study Officials

• Long Sui, Professor

  Obstetrics & Gynecology Hospital of Fudan University

  STUDY CHAIR

• Lan Zhu, Professor

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

Long Sui, Professor

CONTACT

0086-021-33189900; suilong@fudan.edu.cn

Qing Cong, PHD

CONTACT

0086-021-33189900; qingcong@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Women who aged 25 to 65 years are screened for cervical cancer and they are all positive of high-risk HPV.

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: April 16, 2024
• Study Start: April 1, 2024
• Primary Completion: August 1, 2025
• Study Completion: February 1, 2026
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Starting 6 months after publication
• Access Criteria: We will apply for a web address to upload all collected clinical data and trial results. The public can send email or request access to the web if any of them needed. After waiting for the principal investigator's consent, the data would be shared by browsing the website.

Locations

CN (1)