The Mechanism of Vaginal Flora and Its Metabolites in the Pathogenesis of Cervical Cancer

January 23, 2022 updated by: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
The disorder of vaginal microflora and its metabolites is considered to be a facilitating factor to human papillomavirus-mediated cervical cancer. However, the mechanism is still unclear. This study intends to carry out a cross-sectional study and a cohort study. The cross-sectional study intends to recruit 300 premenopausal non-pregnant women, dividing them into five groups, with 60 in each group: HPV negative [Ctrl HPV (-)], HPV positive [Ctrl HPV (+)], low-grade squamous Intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and newly diagnosed invasive cervical cancer (ICC). Obtain basic information through the questionnaire, and collect vaginal secretion and blood samples. At the same time, patients who are diagnosed with cervical cancer for the first time will be included in the cohort study. Collect the same kind of information. The follow-up period is set to be 3 years, and samples will be collected every six months. If any condition changes within the 3 years, samples should be collected. If new treatments are taken, samples should be taken before and after treatment. And if the lesion turns negative after treatment within the 3 years, complete the follow-up. Using 16S rRNA gene sequencing, metabolomics, and immunological methods to determine the vaginal microbiota and its metabolites and inflammation condition, select biomarkers related to the onset of cervical cancer. construct a cervical cancer risk model and outcome prediction model, and reveal the mechanism of vaginal flora and its metabolites in the pathogenesis and development of cervical cancer. Therefore provides a new direction for the prevention and treatment of cervical cancer.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The disorder of vaginal microflora and its metabolites is considered to be a facilitating factor to human papillomavirus-mediated cervical cancer. However, the mechanism is still unclear.

This study intends to carry out a cross-sectional study and a cohort study. The cross-sectional study intends to recruit 300 premenopausal non-pregnant women, dividing them into five groups, with 60 in each group: HPV negative [Ctrl HPV (-)], HPV positive [Ctrl HPV (+)], low-grade squamous Intraepithelial lesion (LSIL group), high-grade squamous intraepithelial lesion (HSIL group) and newly diagnosed invasive cervical cancer (ICC group).

Obtain basic information through the questionnaire, and collect vaginal secretion and blood samples every time the patients review the clincal department as scheduled. At the same time, patients who are diagnosed with cervical cancer for the first time will be included in the cohort study. Collect the same kind of information. The follow-up period is set to be 3 years, and samples will be collected every six months. If any condition changes within the 3 years, samples should be collected. If new treatments are taken, samples should be taken before and after treatment. And if the lesion turns negative after treatment within the 3 years, complete the follow-up.

Using 16S rRNA gene sequencing, metabolomics, and immunological methods to determine the vaginal microbiota and its metabolites and inflammation condition, select biomarkers related to the onset of cervical cancer.

Carry out the genital tract inflammation score calculating, blood inflammatory factors testing, biological information analyzing, and metabolite composition and content in vaginal secretions analyzing.

The purpose of this study is to construct a cervical cancer risk model and outcome prediction model, and reveal the mechanism of vaginal flora and its metabolites in the pathogenesis and development of cervical cancer. Therefore provides a new direction for the prevention and treatment of cervical cancer.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • The Sun Yat-sen Memorial Hospital of Sun Yat-sen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

All patients are selected from the gynecology clinical department of the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.

Description

Inclusion Criteria:

  1. Age 18 to 60 years women;
  2. have a history of sexual life for 3 years or more;
  3. women not in the menstrual period, pregnancy, or puerperium.

Exclusion Criteria:

  1. Women who received antibiotics and antifungal treatment within one month before the sample collection (records);
  2. Women suffering from the following diseases: other cancer, vaginal infections, bacterial vaginosis, vulvar infections, urinary tract infections or sexually transmitted infections including chlamydia, gonorrhea, trichomoniasis and genital herpes, type I or type II diabetes, AIDS Virus positive;
  3. Women with abnormal vaginal secretions or dirt in the vagina, and women who used flushing substances within three weeks before the sample collection;
  4. Have sexual intercourse or use vaginal lubricant within 48 hours before sample collection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ctrl HPV (-)
Patients with normal cervix and HPV negative
Other: This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
Ctrl HPV (+)
Patients with normal cervix and HPV positive
Other: This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
LSIL group
Patients with low-grade squamous Intraepithelial lesion
Other: This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
HSIL group
Patients with high-grade squamous Intraepithelial lesion
Other: This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
ICC group
Patients newly diagnosed invasive cervical cancer
Other: This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.
This project is a clinical observational study. No additional medication or surgical interventions are performed on the subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genital tract inflammation score
Time Frame: immediately after the sample collection
ELISA kit is used to detect the expression levels of 7 cytokines (IL-1α, IL-1β, IL-8, MIP-1β, CCL20, RANTES and TNF-α, etc.) in the vaginal secretions, and determine a cumulative score according to the level of each cytokine. If 3 or more than 3 of the 7 cytokines ranks in the upper quartile of all participants, it's considered high-level reproductive tract inflammation. A score of 5 to 7 is considered high-grade genital tract inflammation, 1 to 5 is low-grade genital tract inflammation, and a score of 0 is no inflammation.
immediately after the sample collection
Blood inflammatory factors
Time Frame: immediately after the sample collection
Use ELISA kit to detect 7 kinds of inflammatory factors (IL-1α, IL-1β, IL-8, MIP-1β, CCL20, RANTES and TNF-α.) in the blood sample.
immediately after the sample collection
16sDNA sequencing and biological information analysis
Time Frame: immediately after the sample collection
Extract DNA with a total bacterial DNA extraction kit, using bacterial DNA as a template, bacterial 16S rDNA V3~V4 variable regions as targets, and barcode-equipped universal primers for PCR amplification. The PCR products will be sequenced using Illumina NovaSeq sequencing technology. After quality control, trimming, denoising, splicing, and chimera removal of the obtained raw data and reads, the high-throughput original base sequence is obtained, and the data will be analyzed using Qiime2 software. Data analysis includes operational unit (OTU) clustering, genetic enrichment analysis, principal component analysis (PCoA), community structure diversity (α and β diversity), and analysis of bacterial genus differences between groups (using linear discriminant effect analysis of LefSe ), correlation analysis, intestinal flora prediction model (random forest model).
immediately after the sample collection
The metabolite composition and content in vaginal secretions
Time Frame: immediately after the sample collection
The non-targeted metabolomics method is used to detect the metabolite composition and content in vaginal secretions. Quantitative analysis of metabolomics in each group, principal component analysis (PCOA, group analysis), differential metabolite spectrum analysis (increased/decreased metabolites in each group), correlation analysis (correlation analysis of inflammatory factors and metabolites). Correlation analysis between microbiology and metabolomics (including correlation analysis between different species and different metabolites, Scatter plot analysis, etc).
immediately after the sample collection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The content of the questionnaire
Time Frame: immediately after the first visit of the patients

The content of the questionnaire includes:

  1. General information: name, place of origin, age, nationality, occupation, education level, family income, etc.
  2. Marriage and childbirth history: menstruation, marital status, pregnancy and parity, history of sexual life, contraceptive methods, etc.
  3. Lifestyle: smoking history, drinking history, sleep time, moderate to high-intensity physical activity, etc.
  4. Disease history and family history: diabetes, hypertension, venereal history, history of gynecological tumors.
  5. Testing and laboratory examinations: height, weight, gynecological examinations, HPV testing, TCT or cervical pathological diagnosis, etc.
immediately after the first visit of the patients

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

  • Study Director: Rao Qunxian, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 1, 2022

Primary Completion (Anticipated)

January 1, 2023

Study Completion (Anticipated)

January 1, 2023

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

December 22, 2021

First Posted (Actual)

January 11, 2022

Study Record Updates

Last Update Posted (Actual)

January 25, 2022

Last Update Submitted That Met QC Criteria

January 23, 2022

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SYSEC-KY-KS-2021-214

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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