Third-Generation Nanopore HPV Integration Site for Precise Prediction of Cervical Cancer Prognosis

NCT06644677 | Completed DMC

• 1 other identifier: CHINTIGER
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cervical Cancers; HPV Testing; Nanopore Sequencing; HPV Integration Site Detection; Rapid Diagnosis

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (1)

• Overall survival

  5 years

Study Arms (1)

Advanced-stage cervical cancer patients group (Stage IIIB and beyond)

Diagnostic Test: HPV integration

Interventions

HPV integration DIAGNOSTIC_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.

Advanced-stage cervical cancer patients group (Stage IIIB and beyond)

Eligibility Criteria

• Age: 75 Years - 78 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

the patient's cells, extracted DNA, or RNA

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 16, 2024
• Study Start: September 19, 2019
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: October 16, 2024

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)