Vaginal Microbiome and HPV Pre-malignant and Cervical Dysplasia

Assessing Personalized Vaginal Microbiome Contributions to HPV-driven Pre-malignant and Malignant Cervical Cancer

In this study, the investigators will prospectively collect, analyze and integrate information regarding vaginal microbiome composition and HPV presence in women with cervical pathologies (high-grade CIN and CC) and controls, to construct a large dataset from patients with pre-cancerous cervical lesions and healthy women, to evaluate the personalized contribution of the vaginal microbiome to the CIN-CC sequence.

Study Overview

• Status: Recruiting
• Conditions: Vaginal Flora Imbalance; Human Papilloma Virus; Cancer Cervix Uterus; Cervical Dysplasia

Detailed Description

Infection with high-risk Human Papillomavirus (HPV) genotypes constitutes a well-recognized risk factor for cervical-carcinoma (CC). High-risk HPV features 10-15% persistence rate, consequently driving precancerous cervical-intraepithelial-neoplasia (CIN) and subsequent progression to CC. Multiple factors are believed to play permissive roles in the progression of CIN/CC , yet a molecular mechanism driving carcinogenesis across the CIN-CC continuum following persistent HPV infection remains elusive. The vaginal microbiome may play a role in the development of CIN-CC carcinogenesis, by modulation of host-immune-response and alteration of cervical microenvironment to become tumor-permissive. While suggested vaginal microbiome contributions include induction of altered epithelial cell adhesion and downregulation of DNA damage responses, no clear mechanism has been proven to date. The loss of Lactobacillus genus dominancy, and the switch to dysbiotic, high-diversity, high-pH, Bacterial Vaginosis (BV) is thought to play a key-role in HPV infection, persistence and carcinogenesis.

the investigators hypothesize that specific vaginal microorganisms may promote HPV persistence, chronic inflammation and progression through the CIN-CC sequence, and the elimination of harmful bacteria or supplementation of beneficial microbes, could possibly reverse HPV persistency and inhibit CIN-CC progression.

The current study consists of recruitment of a human cohort of healthy, CIN and CC patients including vaginal samples and comprehensive metadata collection. The investigators plan to conduct an in-depth characterization of vaginal microbiome to identify associations with HPV, CIN and CC.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Ahinoam Lev Sagie, MD; Phone Number: +972-54-4327178; Email: levsagie@netvision.net.il
• Study Contact Backup: Name: Lilah Tsaitlin Mor, MD; Phone Number: +972-54-7753434; Email: lilah.tsaitlin@gmail.com

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Medical Center
    • Contact: Ahinoam Lev Sagie, MD; Phone Number: +972-54-4327178; Email: levsagie@netvision.net.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

1) Individuals that underwent an HPV PCR cervical screening test and were found to be negative for HPV (healthy controls, n=45) 2) Women that were found to be positive for high risk-HPV but have no cervical dysplasia (n=30) 3) Women who are positive for high risk-HPV and exhibit cervical pathology, either high-CIN (CIN 2-3) or CC (n=15).

Description

Inclusion Criteria:

• Age 25-70
• Attended the clinic for a Pap smear or colposcopy

Exclusion Criteria:

• Patient does not approve sample collection
• Usage of antibiotics in the month prior to clinic visit
• Usage of any vaginal preparation or medication in the week prior to sample collection (anti-fungal, spermicides, lubricant etc.)
• Menstruation
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Controls; Healthy women without HPV in their cervical and vaginal sample
Women with HPV; Women with HPV, with or without cervical intraepithelial neoplasia or carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the microbiome using molecular methods.	Comparison of microbiome profiles between those with HPV compared to controls without HPV.	1 year

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: Ahinoam Lev Sagie, MD, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 15, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Uterine Cervical Diseases; Papilloma; Uterine Cervical Dysplasia; Precancerous Conditions
• Other Study ID Numbers: HMO-812-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No