Condition category
Cancer
Date applied
31/01/2020
Date assigned
21/02/2020
Last edited
21/02/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims.
Persistent infection by a high-risk oncogenic (cancer-causing) type of Human Papillomaviruses (hrHPV) is related to precancerous lesions and invasive cervical cancer. Cervical cancer still remains one of the most frequent cancers in women worldwide.

hrHPV infection is necessary to cause cancer, but other additional factors are needed to be present too. Many factors have been proven to increase the oncogenic ability of hrHPV finally leading to the development of cancer. Among them, in recent years the composition of the vaginal microbiome has been suggested to have a critical role in cervical cancer development, but its role has not yet been made fully clear. Currently, there are no data on the potential importance of the vaginal microbiome in the recovery of patients after surgical removal of cervical cancer.

This study aims to assess if specific types of vaginal microbiota are linked to an increased or decreased possibility of recovery after surgical removal of HPV-related cervical cancer. In addition, the vaginal environment will be characterized, to understand if inflammation is an important factor in this process.

The results will be helpful in understanding if the vaginal microbiome can have a role in clearing HPV infection or in promoting its persistence. This could possibly pave the way to future treatments based on the use of specific bacteria to restore a protective vaginal microbiome and improving the outcomes of patients with, or at risk of, cervical cancer.

Who can participate?
Women aged 30 to 50 years, affected by CIN2-CIN3 cervical lesions

What does the study involve?
The study is only observational, as the only intervention is the surgical treatment of CIN lesion. No pharmacological or other kinds of additional treatment are planned.

What are the possible benefits and risks of participating?
Participating women will be analyzed for their vaginal microbiome and vaginal secretions, thus providing a deeper knowledge of their situation and possible prognosis. Participants are not exposed to any risk.

Where is the study run from?
The gynecological center of the University Hospital of Ferrara (Italy)

When is the study starting and how long is it expected to run for?
April 2017 to February 2020

Who is funding the study?
No specific funds are used for this study. Each investigator will use his/her academic funds to run the study.

Who is the main contact?
Prof Elisabetta Caselli
csb@unife.it

Trial website

Contact information

Type

Scientific

Primary contact

Prof Elisabetta Caselli

ORCID ID

http://orcid.org/0000-0001-6048-9141

Contact details

Section of Microbiology
Department of Chemical and Pharmaceutical Sciences
via Luigi Borsari 46
Ferrara
44121
Italy
+39 0532 455387
elisabetta.caselli@unife.it

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

03

Study information

Scientific title

Vaginal microbiota and chemokine microenvironment in women surgically treated for cervical intraepithelial neoplasia and their association with HPV clearance/persistence

Acronym

Study hypothesis

The vaginal microbiome has been associated with HPV infection, but no data are available on its role in HPV clearance and persistence in women affected by cervical intraepithelial neoplasia lesions with surgical treatment. The aim of the study is to assess this aspect and simultaneously evaluate also the vaginal chemokine profile with particular attention to the pro-inflammatory factors.

Ethics approval

Approved 13/07/2017, the Ethical Committee of the Province of Ferrara (Azienda Ospedaliero, Universitaria di Ferrara, Via Aldo Moro 8, Ferrara 44124; +39 0532 236896, +39 0532 455727; ulrich.wienand@unife.it) ref: 170394

Study design

Longitudinal, observational, cohort, single-centre, prospective study.

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a participant information sheet

Condition

cervical intraepithelial neoplasia, HPV, CIN2, CIN3

Intervention

The study is only observational, as the surgical intervention to remove the CIN lesion is part of the planned clinical treatment for such type of disease.

The study focuses on the characterization of vaginal microbiome and vaginal microenvironment in patients affected by CIN2-CIN3 cervical lesions and undergoing surgical treatment to remove lesions.

Each patient undergoing the surgical treatment of CIN2 or CIN3 lesion, and signing informed consent to participate in the study, will have their vaginal microbiome and vaginal cytokines characterized at baseline (the day of surgical treatment) and after 6 months (follow-up). They will also be assessed by a clinician at baseline and 6 months.

The vaginal microbiome is characterized by molecular biology, using a quantitative real-time PCR microarray detecting and quantifying simultaneously 90 microbial species (including bacteria, mycetes, and protozoa) typically found in vaginosis.

The vaginal environment is characterized by analyzing the presence and concentration of twelve pro-inflammatory cytokines, by ELISA assays. The analyzed cytokines are: IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12, IL17α, IFNγ, and TNFα.

Cervicovaginal samples are collected by sterile rayon swabs put in 0.4 ml of sterile phosphate-buffered saline (PBS) in a 1.5 ml microtube. Collected samples are immediately refrigerated and transported to the laboratory for processing within 3 hours. Total DNA is extracted from the cervicovaginal swab samples upon arrival at the laboratory (within 3 hours from the collection). Extracted DNA is quantified by spectrophotometric reading and checked for amplifiability by a panbacterial PCR and a PCR amplifying a human house-keeping gene (beta-actin)

Vaginal secretions are collected by washings the vaginal cavity with 5 ml of sterile physiological solution. The collected samples are distributed in sterile 1.5 ml microtubes, immediately refrigerated and then frozen at -80°C until use.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

The role of the vaginal microbiome in HPV clearance and persistence in CIN patients measured by quantitative real-time PCR microarray of DNA extracted from cervicovaginal swabs taken at baseline and 6 months

Secondary outcome measures

1. Presence of pro-inflammatory cytokines in the vaginal microbiome measured by ELISA assays of vaginal secretions collected at baseline and 6 months
2. Concentration of pro-inflammatory cytokines in the vaginal microbiome measured by analysis of ELISA assays of vaginal secretions collected at baseline and 6 months

Overall trial start date

01/04/2017

Overall trial end date

29/02/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. High risk HPV-positive patients
2. CIN2 or CIN3 cervical lesions
3. Planned removal of cervical lesions by surgical intervention

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

100

Participant exclusion criteria

1. Pregnancy
2. Lactation
3. Concomitant infections
4. Concomitant neoplasias

Recruitment start date

01/01/2019

Recruitment end date

31/01/2020

Locations

Countries of recruitment

Italy

Trial participating centre

University of Ferrara
via Luigi Borsari 46
Ferrara
44121
Italy

Sponsor information

Organisation

University of Ferrara

Sponsor details

via Luigi Borsari 46
Ferrara
44121
Italy
+39 0532 455387
csb@unife.it

Sponsor type

University/education

Website

http://www.unife.it/

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Investigators plan to publish results as soon as possible, once the enrollment of study participants is complete.

IPD Sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Intention to publish date

31/07/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

11/02/2020: Trial’s existence confirmed by the Ethical Committee of the Province of Ferrara.