Vaginal Microbiome and HPV Pre-malignant and Cervical Dysplasia

Study Overview
=================
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.

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

Conditions
-----------------
Human Papilloma Virus, Vaginal Flora Imbalance, Cancer Cervix Uterus, Cervical Dysplasia

Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>Healthy women without HPV in their cervical and vaginal sample | |
| Women with HPV<br>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 |