Cervical CancersNCT06644677
Third-Generation Nanopore HPV Integration Site for Precise Prediction of Cervical Cancer Prognosis
An observational study of Cervical Cancers and HPV Testing, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
Cervical cancer is a significant health threat to women, with over 500,000 new cases and approximately 342,000 deaths worldwide annually, and about 107,000 new cases in China with 51,000 fatalities. Read more about this study
- Who is it for?
- Ages 75 to 78 years, women only
- Conditions the study is for
- Cervical Cancers, HPV Testing, Nanopore Sequencing
- What is being tested?
- HPV integration
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 19 Sep 2019to 31 Aug 2024
- How long will I take part?
- 5 Years
- Phase
- Observational
- 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 75 to 78 years
- Women only
- No healthy volunteers
- Older adult
Study population: Patients enrolled in the study are those with advanced-stage cervical cancer (Stage IIIB and beyond), with TCT procedures performed by radiation oncologists. During the procedure, sterile physiological cotton balls are used to clean away external cervical secretions. A cytobrush is inserted into the cervical lesion or the squamocolumnar junction within the cervical canal to collect samples, rotated 3-4 times, left in place for several seconds, and then placed into a cell preservation fluid, sealed, and sent for testing. As a therapeutic department, the radiation oncology department is heavily involved in the entire process of diagnosis, treatment, and follow-up for cervical cancer patients. During treatment, patients undergo invasive brachytherapy, which has a higher level of sterility requirements and operational difficulty than TCT procedures, hence they are capable of performing TCT specimen collection.
Who may be able to join
- A. Undergoing radical radiochemotherapy at our institution or a collaborating institution; B. Pathologically confirmed as cervical cancer; C. Diagnosed as an advanced-stage patient (FIGO staging IIIB, IIIC, IVA, IVB), or a patient who has experienced local recurrence or distant metastasis after radical radiochemotherapy; D. Capable of regular follow-up visits; E. The patient or their family can understand the research protocol and are willing to participate in this study, providing written informed consent.
Who cannot join
- A. Confirmed by pathology as neuroendocrine carcinoma of the cervix; B. Have not undergone standardized radical treatment (for the cohort of stage IIIB and later cervical cancer patients, those who have not undergone standardized radical radiochemotherapy must be excluded. For the cohort of patients who have local recurrence or distant metastasis after radical radiochemotherapy, those who have only had cervical cancer surgery and recurrence, and those who have not undergone standardized radiochemotherapy after cervical cancer surgery must be excluded); C. HPV testing is negative, and there is no clear integration site of HPV in the genome; D. The patient or family members are unable to cooperate with the study or cannot provide written informed consent.
Trial locations and contacts
1 site in 1 country.
China1 site
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
About this study
Official title: Development of a Third-Generation Nanopore HPV Integration Site Detection Kit for Precise Prediction of Cervical Cancer Prognosis
Cervical cancer is a significant health threat to women, with over 500,000 new cases and approximately 342,000 deaths worldwide annually, and about 107,000 new cases in China with 51,000 fatalities. Current screening methods include HPV testing, cytology, colposcopy, and biopsy, but none can detect HPV genome integration in persistently positive patients.
Our team has analyzed over 200 cervical cell samples using third-generation nanopore technology, focusing on HPV integration sites. We've developed a proprietary long-fragment capture and sequencing method (reads averaging 2-5kb) that identifies precise HPV insertion points and detects the complete Human-Virus-Human (H-V-H) viral insertion sequence. We found overlaps in HPV integration genes across different stages of cervical intraepithelial neoplasia (CIN) and in cancer patients with recurrence and metastasis, suggesting potential biomarkers for tumor progression and poor prognosis.
We also analyzed HPV sequence proportions and gene insertion numbers in samples from patients before and after radical radiochemotherapy, providing insights into treatment efficacy and prognosis. Our study aims to use a domestic nanopore sequencing platform and probes tailored to Chinese HPV infection patterns to detect integration sites in late-stage cervical cancer and post-treatment recurrence/metastasis patients. We aim to optimize our method to complete the entire detection process within eight hours, expanding the technology's application in point-of-care diagnostics and decentralization.
Read the detailed description
Cervical cancer is the most common malignant tumor of the reproductive tract, posing a serious threat to women's health. According to data from the World Health Organization (WHO), there are over 500,000 new cases of cervical cancer globally each year, with approximately 342,000 deaths. In China, there are about 107,000 new cases annually, with around 51,000 patients dying from cervical cancer. The market for detection is vast and continues to grow. The main methods of examination after cervical cancer screening and treatment include HPV testing, cytological screening, colposcopy, and cervical biopsy. All HPV tests on the market are qualitative and semi-quantitative, and there is currently no product on the market that can detect whether HPV integrates into the genome in patients with persistent HPV positivity.
Our team, in previous research, enrolled over 200 cervical cell samples, including those from patients with high-risk HPV infection without intraepithelial neoplasia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and samples from locally advanced cervical cancer before and after radiochemotherapy at multiple time points. Using third-generation nanopore technology, we have completed experiments and analysis on 93 cervical cell samples. Based on the probe hybridization capture principle, we enriched and sequenced the integration sites of HPV viral DNA. Preliminary conclusions are as follows:
- Through our self-developed experimental technology process, we achieved long-fragment virus capture and sequencing (average read length 2-5kb), identifying HPV insertion sites and more precise genomic localization. Moreover, nanopore long-fragment sequencing can detect the complete Human-Virus-Human (H-V-H) viral insertion structure sequence.
- There is a certain proportion of overlap between the HPV insertion genes in the inflammation group, CIN I, CIN II, CIN III groups, and the HPV insertion genes in cancer patients with recurrence and metastasis, which can further assist in screening for molecular markers related to tumor progression and poor prognosis.
- The proportion of HPV sequences and the number of inserted genes in patient samples before and after radical radiochemotherapy can further assess the effectiveness of treatment and prognosis, providing support data for pre-treatment intervention and risk warning.
The goal of this study is to collaborate with a domestically produced nanopore sequencing platform and self-designed probes targeting the characteristics of HPV infection in the Chinese population. We aim to conduct insertion site detection on cohorts of late-stage cervical cancer (stage IIIB and beyond) and patients with recurrence and metastasis after radical cervical cancer radiochemotherapy. We will further establish and optimize the long-fragment virus enrichment method and nanopore sequencing experimental process to complete the entire detection process within one working day (8 hours). This will also expand the application of the technology in bedside diagnosis and decentralized directions.
- Conditions
- Cervical Cancers, HPV Testing, Nanopore Sequencing, HPV Integration Site Detection, Rapid Diagnosis
- Being tested
- HPV integration
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HPV integrationDiagnostic test
Collect late-stage cervical cancer (Stage IIIB and beyond) and post-treatment recurrence and metastasis specimens (TCT, tissue) associated with HPV infection. Utilize third-generation nanopore technology to detect the integration sites of HPV DNA based on the principle of probe hybridization capture. Obtain information on HPV integration and hot spot genes in the samples. By analyzing the integration of HPV in primary and recurrent/metastatic tissues, identify insertions and gene alterations associated with recurrence/metastasis, and develop a predictive formula.
| Study group | Role | What they receive |
|---|---|---|
| Advanced-stage cervical cancer patients group (Stage IIIB and beyond) | Not described Receives: Diagnostic Test: HPV integration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Disease-free survival was defined as the period from the diagnosis of cervical cancer to events that included death or disease progression at local, regional, or distant sites or until the date of the last follow-up.
Measured: 5 years
Secondary outcomes (1)
Overall survival
Overall survival was defined as the period from the diagnosis of cervical cancer to the date of death or last follow-up.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2024
- Study start19 Sep 2019
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical CancersStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhang Fuquan, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06644677
- Sponsor's protocol ID
- CHINTIGER
- Status last verified
- Sep 2019
- First submitted
- 15 Oct 2024
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To protect the privacy of the patients
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Third-Generation Nanopore HPV Integration Site Detection Kit for Precise Prediction of Cervical Cancer Prognosis
- ClinicalTrials.gov ID
- NCT06644677
- Acronym / sponsor ID
- CHINTIGER
- Conditions
- Cervical Cancers, HPV Testing, Nanopore Sequencing, HPV Integration Site Detection, Rapid Diagnosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 19 Sep 2019 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 16 Oct 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.
Cervical cancer is a significant health threat to women, with over 500,000 new cases and approximately 342,000 deaths worldwide annually, and about 107,000 new cases in China with 51,000 fatalities. Current screening methods include HPV testing, cytology, colposcopy, and biopsy, but none can detect HPV genome integration in persistently positive patients.
Our team has analyzed over 200 cervical cell samples using third-generation nanopore technology, focusing on HPV integration sites. We've developed a proprietary long-fragment capture and sequencing method (reads averaging 2-5kb) that identifies precise HPV insertion points and detects the complete Human-Virus-Human (H-V-H) viral insertion sequence. We found overlaps in HPV integration genes across different stages of cervical intraepithelial neoplasia (CIN) and in cancer patients with recurrence and metastasis, suggesting potential biomarkers for tumor progression and poor prognosis.
We also analyzed HPV sequence proportions and gene insertion numbers in samples from patients before and after radical radiochemotherapy, providing insights into treatment efficacy and prognosis. Our study aims to use a domestic nanopore sequencing platform and probes tailored to Chinese HPV infection patterns to detect integration sites in late-stage cervical cancer and post-treatment recurrence/metastasis patients. We aim to optimize our method to complete the entire detection process within eight hours, expanding the technology's application in point-of-care diagnostics and decentralization.
Detailed description
Cervical cancer is the most common malignant tumor of the reproductive tract, posing a serious threat to women's health. According to data from the World Health Organization (WHO), there are over 500,000 new cases of cervical cancer globally each year, with approximately 342,000 deaths. In China, there are about 107,000 new cases annually, with around 51,000 patients dying from cervical cancer. The market for detection is vast and continues to grow. The main methods of examination after cervical cancer screening and treatment include HPV testing, cytological screening, colposcopy, and cervical biopsy. All HPV tests on the market are qualitative and semi-quantitative, and there is currently no product on the market that can detect whether HPV integrates into the genome in patients with persistent HPV positivity.
Our team, in previous research, enrolled over 200 cervical cell samples, including those from patients with high-risk HPV infection without intraepithelial neoplasia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and samples from locally advanced cervical cancer before and after radiochemotherapy at multiple time points. Using third-generation nanopore technology, we have completed experiments and analysis on 93 cervical cell samples. Based on the probe hybridization capture principle, we enriched and sequenced the integration sites of HPV viral DNA. Preliminary conclusions are as follows:
- Through our self-developed experimental technology process, we achieved long-fragment virus capture and sequencing (average read length 2-5kb), identifying HPV insertion sites and more precise genomic localization. Moreover, nanopore long-fragment sequencing can detect the complete Human-Virus-Human (H-V-H) viral insertion structure sequence.
- There is a certain proportion of overlap between the HPV insertion genes in the inflammation group, CIN I, CIN II, CIN III groups, and the HPV insertion genes in cancer patients with recurrence and metastasis, which can further assist in screening for molecular markers related to tumor progression and poor prognosis.
- The proportion of HPV sequences and the number of inserted genes in patient samples before and after radical radiochemotherapy can further assess the effectiveness of treatment and prognosis, providing support data for pre-treatment intervention and risk warning.
The goal of this study is to collaborate with a domestically produced nanopore sequencing platform and self-designed probes targeting the characteristics of HPV infection in the Chinese population. We aim to conduct insertion site detection on cohorts of late-stage cervical cancer (stage IIIB and beyond) and patients with recurrence and metastasis after radical cervical cancer radiochemotherapy. We will further establish and optimize the long-fragment virus enrichment method and nanopore sequencing experimental process to complete the entire detection process within one working day (8 hours). This will also expand the application of the technology in bedside diagnosis and decentralized directions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Advanced-stage cervical cancer patients group (Stage IIIB and beyond) | – | Diagnostic Test: HPV integration |
Who may qualify
- Ages
- 75 to 78 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Patients enrolled in the study are those with advanced-stage cervical cancer (Stage IIIB and beyond), with TCT procedures performed by radiation oncologists. During the procedure, sterile physiological cotton balls are used to clean away external cervical secretions. A cytobrush is inserted into the cervical lesion or the squamocolumnar junction within the cervical canal to collect samples, rotated 3-4 times, left in place for several seconds, and then placed into a cell preservation fluid, sealed, and sent for testing. As a therapeutic department, the radiation oncology department is heavily involved in the entire process of diagnosis, treatment, and follow-up for cervical cancer patients. During treatment, patients undergo invasive brachytherapy, which has a higher level of sterility requirements and operational difficulty than TCT procedures, hence they are capable of performing TCT specimen collection.
Key inclusion criteria (1 listed)
- A. Undergoing radical radiochemotherapy at our institution or a collaborating institution; B. Pathologically confirmed as cervical cancer; C. Diagnosed as an advanced-stage patient (FIGO staging IIIB, IIIC, IVA, IVB), or a patient who has experienced local recurrence or distant metastasis after radical radiochemotherapy; D. Capable of regular follow-up visits; E. The patient or their family can understand the research protocol and are willing to participate in this study, providing written informed consent.
Key exclusion criteria (1 listed)
- A. Confirmed by pathology as neuroendocrine carcinoma of the cervix; B. Have not undergone standardized radical treatment (for the cohort of stage IIIB and later cervical cancer patients, those who have not undergone standardized radical radiochemotherapy must be excluded. For the cohort of patients who have local recurrence or distant metastasis after radical radiochemotherapy, those who have only had cervical cancer surgery and recurrence, and those who have not undergone standardized radiochemotherapy after cervical cancer surgery must be excluded); C. HPV testing is negative, and there is no clear integration site of HPV in the genome; D. The patient or family members are unable to cooperate with the study or cannot provide written informed consent.
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 |
|---|---|---|
| HPV integrationCollect late-stage cervical cancer (Stage IIIB and beyond) and post-treatment recurrence and metastasis specimens (TCT, tissue) associated with HPV infection. Utilize third-generation nanopore technology to detect the integration sites of HPV DNA based on the principle of probe hybridization capture. Obtain information on HPV integration and hot spot genes in the samples. By analyzing the integration of HPV in primary and recurrent/metastatic tissues, identify insertions and gene alterations associated with recurrence/metastasis, and develop a predictive formula. | Diagnostic test | Advanced-stage cervical cancer patients group (Stage IIIB and beyond) |
Primary outcome
Disease-free survival
Time frame: 5 years
Disease-free survival was defined as the period from the diagnosis of cervical cancer to events that included death or disease progression at local, regional, or distant sites or until the date of the last follow-up.
1 secondary outcome
Overall survival
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Individual participant dataSharing planned: No. To protect the privacy of the patients
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cervical Cancers and HPV Testing, run by Peking Union Medical College Hospital 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 16 Oct 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Oct 2024.