Precancerous Cervical LesionMTTRIHPWNCT06366516
Role of Methylation Test Triage in HPV Positive Women
A study testing Methylation Test in people with Precancerous Cervical Lesion, run by Obstetrics & Gynecology Hospital of Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 65 years, women only
- Conditions the study is for
- Precancerous Cervical Lesion
- What is being tested?
- Methylation Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10,000 participants
- Where
- 1 siteChina
- Study dates
- Apr 2024to Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged 25~65 years undergoing cervical cancer screening
- normal for cytology and positive for hrHPV
- informed consent was obtained
Who cannot join
- 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
- do not meet the inclusion criteria
- give up the trial or naturally dropped out of the follow-up during the observation process
- people who asked to withdraw
Trial locations and contacts
1 site in 1 country.
China1 site
Obstetrics and Gynecology Hospital of Fudan University
Shanghai, Shanghai Municipality, 200011
Long Sui, Professor, 0086-021-33189900, suilong@fudan.edu.cn
Qing Cong, PHD, 0086-021-33189900, qingcong@fudan.edu.cn
About this study
Official title: Clinical Validation of ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671 Methylation in HPV Positive Women: a Multi-center RCT From China
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.
Read the detailed description
The study is divided into two phases, a baseline (cross-sectional) phase and a 1-year follow-up phase. Women who meet the clinical endpoint (i.e. histopathologically confirmed ≥CIN2 after baseline colposcopy/biopsy) are withdrawn from the study. Participants who do not meet the primary endpoint/treat at baseline will invited to participate in the follow-up phase of the trial. Participants included in the follow-up phase are underwent HPV, cytology, and methylation tests at 6 months and 1 year after baseline.Similar to the baseline phase,participants were referred to colposcopy/biopsy if any of the cytology and HPV tests result is positive.
- Conditions
- Precancerous Cervical Lesion
- Being tested
- Methylation Test
- Keywords
- Human papillomavirus, High-grade squamous intraepithelial lesion, Methylation, Cervical cancer screening, Triage, Adenocarcinoma in Situ, Cytology
- Medical subject headings
- Squamous Intraepithelial Lesions, Adenocarcinoma in Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylation TestDiagnostic test
Also called Liquid-based Cytology Test, High-risk HPV test, Colposcopy, Biopsy
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Methylation Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of enrollment until the date of first documented CIN2+,assessed up to 12 months
Secondary outcomes (1)
KAPPA value of methylation test.
KAPPA value is the secondary variable of methylation test which need to meet statistical criteria.
Measured: From date of enrollment until the date of first documented CIN2+,assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2024
- Study startApr 2024 (estimated)
- Primary completionAug 2025 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Precancerous Cervical LesionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Women who aged 25 to 65 years are screened for cervical cancer and they are all positive of high-risk HPV.
- Masking
- None (open label)
- Enrolment
- 10,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Obstetrics & Gynecology Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Peking Union Medical College Hospital, Chengdu Women's and Children's Central Hospital, Guangdong Women and Children Hospital, Second Hospital of Jilin University, First Affiliated Hospital of Xinjiang Medical University, Third Affiliated Hospital of Zhengzhou University
- Responsible party
- Sponsor
- Investigators
- Long Sui, Professor, Study chair, Obstetrics & Gynecology Hospital of Fudan UniversityLan Zhu, Professor, Study chair, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06366516
- Sponsor's protocol ID
- FUOBGY2024-23
- Acronym
- MTTRIHPW
- Status last verified
- Apr 2024
- First submitted
- 27 Mar 2024
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected data from participants will be shared，including age of patients, the results of cytological examination/high-risk HPV genotyping/methylation test/histopathological, colposcopy impression, and whether cervical conization or hysterectomy were performed before.
Publications
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.
PubMed 32619334Giorgi 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.
PubMed 32745170van 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.
PubMed 35266975Dovnik 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.
PubMed 37047452Mazurec 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.
PubMed 37894462Yang 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.
PubMed 32408396Stoler 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.
PubMed 31490545Wright 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.
PubMed 34536311
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Validation of ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671 Methylation in HPV Positive Women: a Multi-center RCT From China
- ClinicalTrials.gov ID
- NCT06366516
- Acronym / sponsor ID
- MTTRIHPW / FUOBGY2024-23
- Conditions
- Precancerous Cervical Lesion
- Keywords
- Human papillomavirus, High-grade squamous intraepithelial lesion, Methylation, Cervical cancer screening, Triage, Adenocarcinoma in Situ, Cytology
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10,000 participants (estimated)
- Lead sponsor
- Obstetrics & Gynecology Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- Peking Union Medical College Hospital, Chengdu Women's and Children's Central Hospital, Guangdong Women and Children Hospital, Second Hospital of Jilin University, First Affiliated Hospital of Xinjiang Medical University, Third Affiliated Hospital of Zhengzhou University
- Study start
- Apr 2024 (estimated)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 16 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study is divided into two phases, a baseline (cross-sectional) phase and a 1-year follow-up phase. Women who meet the clinical endpoint (i.e. histopathologically confirmed ≥CIN2 after baseline colposcopy/biopsy) are withdrawn from the study. Participants who do not meet the primary endpoint/treat at baseline will invited to participate in the follow-up phase of the trial. Participants included in the follow-up phase are underwent HPV, cytology, and methylation tests at 6 months and 1 year after baseline.Similar to the baseline phase,participants were referred to colposcopy/biopsy if any of the cytology and HPV tests result is positive.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Women who aged 25 to 65 years are screened for cervical cancer and they are all positive of high-risk HPV.
| Arm | Type | Receives |
|---|---|---|
| Women aged 25-65 years with high-risk HPV infection. | Experimental | Diagnostic Test: Methylation TestTen thousand women were recruited who aged 25-65 years and they are positive for high-risk HPV. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- aged 25~65 years undergoing cervical cancer screening
- normal for cytology and positive for hrHPV
- informed consent was obtained
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylation TestAlso: Liquid-based Cytology Test, High-risk HPV test, Colposcopy, BiopsyParticipants 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. | Diagnostic test | Women aged 25-65 years with high-risk HPV infection. |
Primary outcome
The sensitivity and specificity of methylation test in detecting CIN2+.
Time frame: From date of enrollment until the date of first documented CIN2+,assessed up to 12 months
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.
1 secondary outcome
KAPPA value of methylation test.
Time frame: From date of enrollment until the date of first documented CIN2+,assessed up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Background: PubMed 32619334Kremer 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.
- Results publication: PubMed 32745170Giorgi 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.
- Results publication: PubMed 35266975van 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.
- Results publication: PubMed 37047452Dovnik 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.
- Results publication: PubMed 37894462Mazurec 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.
- Results publication: PubMed 32408396Yang 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.
- Results publication: PubMed 31490545Stoler 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.
- Results publication: PubMed 34536311Wright 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.
- Individual participant dataSharing planned: Yes. All collected data from participants will be shared，including age of patients, the results of cytological examination/high-risk HPV genotyping/methylation test/histopathological, colposcopy impression, and whether cervical conization or hysterectomy were performed before.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Long Sui, Professor study chair
Obstetrics & Gynecology Hospital of Fudan University
Lan Zhu, Professor study chair
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methylation Test in people with Precancerous Cervical Lesion, run by Obstetrics & Gynecology Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Long Sui, Professor (0086-021-33189900, suilong@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The sensitivity and specificity of methylation test in detecting CIN2+. (time frame: From date of enrollment until the date of first documented CIN2+,assessed up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06366516, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.