Cervical Intraepithelial Neoplasia Grade 2NCT05624827
The Role of FAM19A4 and Hsa-mir-124 Methylation in Predicting Prognosis of Untreated Cervical Intraepithelial Neoplasia 2 (CIN 2)
A study testing Testing DNA methylation test for predicting prognosis of untreated CIN 2 in people with Cervical Intraepithelial Neoplasia Grade 2 and DNA Methylation, run by University Medical Centre Maribor at 1 site in Slovenia.
Trial summary
High-risk precancerous cervical lesions are divided into stage 2 and 3 cervical intraepithelial neoplasia (CIN 2 and 3). CIN 3 represents a direct pre-stage of invasive cancer, has a high rate of progression and a high degree of agreement with the final histological diagnosis. Read more about this study
- Who is it for?
- Ages 20 to 36 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cervical Intraepithelial Neoplasia Grade 2, DNA Methylation
- What is being tested?
- Testing DNA methylation test for predicting prognosis of untreated CIN 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Sep 2021to 1 May 2024
- 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 20 to 36 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Histologically confirmed CIN 2 (with biopsy of colposcopically suspicious changes in the cervix)
- Age under 30 years
- Satisfactory colposcopy (transformation zone fully visible)
- Size of change below 75% of transformation zone
- The change in the ectocervix is fully visible
- Age 30-35 years, if the patient is non-smoker and the change in the cervix does not exceed 50% of the area of the transformation zone
- Signing an informed consent to participate in the survey
- Willingness to perform inspections every 6 months
Who cannot join
- Age 36 years or older
- Unsatisfactory colposcopy (transformation zone not fully visible)
- Size of change exceeds 75% of the transformation zone
- The change in the ectocervix is not completely visible
- Age 30-35 years for smokers or if the change exceeds 50% of the area of the transformation zone
- Suspicted glandular precancerous changes
Show all 15Show fewer
- Histologically verified CIN 2 with cytological changes of glandular cells
- Colposcopically suspected invasive disease
- Histologically verified CIN 2 and histologically verified AIS
- Histologically verified CIN 2 and histologically verified invasive cancer elsewhere in the cervix
- Refusal to sign participation in the survey
- Unwillingness to perform control examinations
- Weakness of an immune system
- Cervical conization performed in the past
- Treatment with local immunomodulators
Trial locations and contacts
1 site in 1 country.
Slovenia1 site, 1 recruiting
- Recruiting
University Medical Centre Maribor
Maribor, 2000
Milena Miklus, MD
About this study
High-risk precancerous cervical lesions are divided into stage 2 and 3 cervical intraepithelial neoplasia (CIN 2 and 3). CIN 3 represents a direct pre-stage of invasive cancer, has a high rate of progression and a high degree of agreement with the final histological diagnosis. In CIN 2 lesions, the rate of agreement with the final histological diagnosis is lower and the rate of spontaneous regression is higher. Due to the higher rate of regression and possible complications after excisional treatment, conservative active monitoring can be considered in selected young CIN 2 patients. A recent meta-analysis reported a high rate of spontaneous clinical regression of CIN 2, particularly in women under 30 years old. There are currently no prospectively validated prognostic biomarkers to determine which CIN 2 will progress to higher grade and which will regress to lower grade of change. Recent research has studied HPV methylation and microbiome analysis as biomarkers. A number of studies have shown that host cell DNA methylation levels in cervical scrapes increase with underlying cervical disease severity and are highest in cervical cancer. DNA methylation involves the covalent binding of a methyl group to the 5´ position of a cytosine molecule in CpG dinucleotides. Besides global hypomethylation, the overall loss of methylation during carcinogenesis, resulting in chromosomal instability, and the silencing of tumour suppressor genes by local hypermethylation of CpG-rich promoter regions contribute to cancer development. Gene promoter methylation can be easily accessed by sensitive, quantitative methylation-specific PCR providing an objective test outcome. The aim of this study was to determine the effect of the methylation rate of two suppressor genes- FAM19A4 and hsa-mir-124 on the rate of CIN 2 regression, persistence or progression in women younger than 36 years (≤35 years old).
- Being tested
- Testing DNA methylation test for predicting prognosis of untreated CIN 2
- Keywords
- CIN 2 prognosis, DNA hypermethylation, FAM19A4, hsa-mir-124, tumor suppressor genes, diagnostic implications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testing DNA methylation test for predicting prognosis of untreated CIN 2Diagnostic test
After being diagnosed with CIN 2, patients will first be contacted by telephone and invited to participate in the study. If patients agree to participate in the research, they will sign a consent to participate in the research. After that, we will perform a colposcopy and take a cervical swab for analysis with the QIAsure Methylation Test Kit (Qiagen, Gaithersburg, USA), which will determine the methylation of tumor suppressor genes FAM19A4 and has-mir-124. Patients will complete a questionnaire. The total duration of tracking in both groups will be two years. The QIAsure Methylation Test will be performed to analyze methylation. It is a methylation-specific PCR test that detects hypermethylation of the tumor promoter suppressor genes FAM19A4 and has-mir-124. The samples on which we will use this test are bisulfite-converted DNA obtained by triage test for high-risk HPV - Hybrid Capture 2 HPV DNA Test (hc2, Qiagen, Gaithersburg, USA).
| Study group | Role | What they receive |
|---|---|---|
| Women with CIN 2 and under 36 years old | Experimental | We will analyze patients under 36 years old (≤ 35) with histological confirmed CIN 2 lesions and without any additional risk factors. Receives: Diagnostic Test: Testing DNA methylation test for predicting prognosis of untreated CIN 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of the degree of methylation on progression of CIN 2
The primary clinical outcome will be the effect of the degree of methylation on the progression of CIN 2 to CIN 3+ (CIN 3 and cervical cancer).
Measured: two years
Secondary outcomes (1)
Rate of progression of CIN 2
The secondary clinical outcome will be the rate of progression of CIN 2 to CIN 3+, the rate of clinical decline to normal histological picture (˂ CIN 1) and the rate of persistence of precancerous change after two years (CIN 2 or persistent CIN 1).
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start1 Sep 2021
- Primary completion1 Sep 2023 (estimated)
- Study completion1 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cervical Intraepithelial Neoplasia Grade 2Studies 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Maribor
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624827
- Sponsor's protocol ID
- IRP-2021/02-04
- Status last verified
- May 2022
- First submitted
- 14 Nov 2022
- Last updated
- 22 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Miklus M, Poljak M, Mlakar J, Cokan A, Pakiz M, Knez J, Al-Mahdawi L, Roskar L, Gorenjak M, Ostrbenk A, Domjanic GG, Dovnik A. The Role of Methylation Marker FAM19A4/mir124-2 and HPV Genotype in Active Surveillance of Women With Cervical Intraepithelial Neoplasia Grade 2 (CIN2). J Med Virol. 2026 Oct;98(10):e71175. doi: 10.1002/jmv.71175.
PubMed 42867141
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of FAM19A4 and Hsa-mir-124 Methylation in Predicting Prognosis of Untreated Cervical Intraepithelial Neoplasia 2 (CIN 2)
- ClinicalTrials.gov ID
- NCT05624827
- Acronym / sponsor ID
- IRP-2021/02-04
- Keywords
- CIN 2 prognosis, DNA hypermethylation, FAM19A4, hsa-mir-124, tumor suppressor genes, diagnostic implications
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Medical Centre MariborUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 May 2024 (estimated)
- First posted
- 22 Nov 2022 (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.
High-risk precancerous cervical lesions are divided into stage 2 and 3 cervical intraepithelial neoplasia (CIN 2 and 3). CIN 3 represents a direct pre-stage of invasive cancer, has a high rate of progression and a high degree of agreement with the final histological diagnosis. In CIN 2 lesions, the rate of agreement with the final histological diagnosis is lower and the rate of spontaneous regression is higher. Due to the higher rate of regression and possible complications after excisional treatment, conservative active monitoring can be considered in selected young CIN 2 patients. A recent meta-analysis reported a high rate of spontaneous clinical regression of CIN 2, particularly in women under 30 years old. There are currently no prospectively validated prognostic biomarkers to determine which CIN 2 will progress to higher grade and which will regress to lower grade of change. Recent research has studied HPV methylation and microbiome analysis as biomarkers. A number of studies have shown that host cell DNA methylation levels in cervical scrapes increase with underlying cervical disease severity and are highest in cervical cancer. DNA methylation involves the covalent binding of a methyl group to the 5´ position of a cytosine molecule in CpG dinucleotides. Besides global hypomethylation, the overall loss of methylation during carcinogenesis, resulting in chromosomal instability, and the silencing of tumour suppressor genes by local hypermethylation of CpG-rich promoter regions contribute to cancer development. Gene promoter methylation can be easily accessed by sensitive, quantitative methylation-specific PCR providing an objective test outcome. The aim of this study was to determine the effect of the methylation rate of two suppressor genes- FAM19A4 and hsa-mir-124 on the rate of CIN 2 regression, persistence or progression in women younger than 36 years (≤35 years old).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Women with CIN 2 and under 36 years old | Experimental | Diagnostic Test: Testing DNA methylation test for predicting prognosis of untreated CIN 2We will analyze patients under 36 years old (≤ 35) with histological confirmed CIN 2 lesions and without any additional risk factors. |
Who may qualify
- Ages
- 20 to 36 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Histologically confirmed CIN 2 (with biopsy of colposcopically suspicious changes in the cervix)
- Age under 30 years
- Satisfactory colposcopy (transformation zone fully visible)
- Size of change below 75% of transformation zone
- The change in the ectocervix is fully visible
Key exclusion criteria (15 listed)
- Age 36 years or older
- Unsatisfactory colposcopy (transformation zone not fully visible)
- Size of change exceeds 75% of the transformation zone
- The change in the ectocervix is not completely visible
- Age 30-35 years for smokers or if the change exceeds 50% of the area of the transformation zone
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 |
|---|---|---|
| Testing DNA methylation test for predicting prognosis of untreated CIN 2After being diagnosed with CIN 2, patients will first be contacted by telephone and invited to participate in the study. If patients agree to participate in the research, they will sign a consent to participate in the research. After that, we will perform a colposcopy and take a cervical swab for analysis with the QIAsure Methylation Test Kit (Qiagen, Gaithersburg, USA), which will determine the methylation of tumor suppressor genes FAM19A4 and has-mir-124. Patients will complete a questionnaire. The total duration of tracking in both groups will be two years. The QIAsure Methylation Test will be performed to analyze methylation. It is a methylation-specific PCR test that detects hypermethylation of the tumor promoter suppressor genes FAM19A4 and has-mir-124. The samples on which we will use this test are bisulfite-converted DNA obtained by triage test for high-risk HPV - Hybrid Capture 2 HPV DNA Test (hc2, Qiagen, Gaithersburg, USA). | Diagnostic test | Women with CIN 2 and under 36 years old |
Primary outcome
Impact of the degree of methylation on progression of CIN 2
Time frame: two years
The primary clinical outcome will be the effect of the degree of methylation on the progression of CIN 2 to CIN 3+ (CIN 3 and cervical cancer).
1 secondary outcome
Rate of progression of CIN 2
Time frame: two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2022.
- Derived from this study: PubMed 42867141Miklus M, Poljak M, Mlakar J, Cokan A, Pakiz M, Knez J, Al-Mahdawi L, Roskar L, Gorenjak M, Ostrbenk A, Domjanic GG, Dovnik A. The Role of Methylation Marker FAM19A4/mir124-2 and HPV Genotype in Active Surveillance of Women With Cervical Intraepithelial Neoplasia Grade 2 (CIN2). J Med Virol. 2026 Oct;98(10):e71175. doi: 10.1002/jmv.71175.
- Individual participant dataSharing planned: Yes
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Testing DNA methylation test for predicting prognosis of untreated CIN 2 in people with Cervical Intraepithelial Neoplasia Grade 2 and DNA Methylation, run by University Medical Centre Maribor at 1 site in Slovenia.
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 8 inclusion and 15 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 22 Nov 2022. 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 Slovenia. 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 Milena Miklus, MD (+386 2 321 2178, milena.rmus4@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of the degree of methylation on progression of CIN 2 (time frame: two years). 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 NCT05624827, which also lists 1 linked publication.
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 22 Nov 2022.