Clinical trial NCT05640700: Vaginal Microbiome and HPV Pre-malignant and Cervical Dysplasia
Official title: Assessing Personalized Vaginal Microbiome Contributions to HPV-driven Pre-malignant and Malignant Cervical Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Human Papilloma Virus
Vaginal Flora Imbalance
Cancer Cervix Uterus
Cervical Dysplasia
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2022-12-07
Enrollment: 90
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Characterization of the microbiome using molecular methods.
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
Study officials:
affiliation: Hadassah Medical Organization
name: Ahinoam Lev Sagie, MD
role: PRINCIPAL_INVESTIGATOR
References: