Plain English Summary
Background and study aims
Human papilloma virus (HPV) are common viruses that affect the skin and moist membranes lining parts of the body, for example, the mouth, cervix and vagina. Most people will be infected with HPV at some point in their lives. It rarely causes any problems and goes away on its own. Some HPVs can cause changes to the cells of the cervix. These changed cells are then more likely to become cancerous. HPV infection is a necessary, but not sufficient cause for the development of cervical cancer and its precursors (that is, pre-cancerous changes).Our knowledge about human microbiome (the microorganisms – such as bacteria and viruses - on and in our body) has increased vastly after the development of novel sequencing methods and only recently HPV clearance rate (i.e how long it takes for the infection to go away) was shown to be dependent on vaginal microbiome type. Since development of cervical cancer requires HPV infection, studying the interplay between vaginal microbiome, mucosal immune system (the part of the immune system that protects mucous membranes) , HPV status (state of infection, if any), and the clinical presentation of the disease simultaneously is crucial for understanding why only a fraction of women infected with HPV develop cervical cancer. The aim of this study is to investigate whether the removal of abnormal (mucus secreting) cells during LEEP (loop electrosurgical excision procedure) treatment affects the immune defence system of the cervix, leading to an inbalance in the normal vaginal microbiome (dysbiosis) and possibly increasing the likelihood of inflammation and prolonged HPV infection.
Who can participate?
Women aged between 18-45, not pregnant and have been referred to colposcopy (a procedure to check for abnormal cells in a womans cervix or vagina) due to an abnormal Pap smear result.
What does the study involve?
Participants are placed into one of three groups. Those in group 1 are referred to colposcopy and LEEP treatment. Those in group 2 are referred to colposcopy, but do not have lesions (pre-cancerous changes) requiring LEEP treatment. Those in group 3 (the control group) have been recruited during routine Pap smear screening. Samples are taken from all participants before colposcopy and then six months later.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Helsinki University Central Hospital (HUCH) Womens Hospital
When is the study starting and how long is it expected to run for?
September 2015 to December 2020
Who is funding the study?
Helsinki University Central Hospital
Who is the main contact?
Dr Pekka Nieminen
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
The association between preterm birth, vaginal microbiome, immune defence and HPV among women with cervical precancer: an observational single-center study
Acronym
MI-HPV
Study hypothesis
Our hypothesis is that the removal of mucus secreting cells in LEEP treatment compromises cervical immune defense and thus predisposes to ascending infection or inflammatory response against normal flora altering microbiota in the vagina and the microbiota might be dysbiotic in the first place to allow prolonged HPV-infection.
Ethics approval
University of Helsinki Institutional Review Board, 30/01/2014, ref: 21/13/03/2014
Study design
Observational single-center study
Primary study design
Observational
Secondary study design
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
HPV infection
Intervention
We will recruit women referred to colposcopy due to an abnormal Pap smear result, age 18 to 45, who are not pregnant and have no previous cervical operation. There are then allocated to one of three groups.
1. Main study group: Women referred to colposcopy and LEEP treatment
2. Control group 1: Women referred to colposcopy, but do not have lesions requiring LEEP treatment.
3. Control group 2: Women recruited during routine Pap smear screening at HUSLab
Samples are taken before colposcopy and after six months follow-up, during the first control visit.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measures
1. Presence of immunomarkers, using multiplex ELISA
2. HPV-status, using PCR
3. Analysis of microbiota, by measuring hypervariable 16S
Results are compared between patients receiving treatment for HPV lesions with those that do not require treatment for lesions. Measurements are taken at baseline and 6 months later.
Secondary outcome measures
1. Presence of immunomarkers
2. HPV-status
3. Analysis of microbiota
Results are compared between patients with HPV at a colposcopy clinic to "healthy" controls undergoing Pap screening. Measurements are taken at baseline and 6 months later.
Overall trial start date
17/09/2015
Overall trial end date
31/12/2020
Reason abandoned
Eligibility
Participant inclusion criteria
Healthy volunteers and colposcopy patients.
Participant type
Mixed
Age group
Adult
Gender
Female
Target number of participants
50+50+50
Participant exclusion criteria
1. Pregnancy
2. Vaginal bleeding
3. Previous cervical surgery
Recruitment start date
17/09/2015
Recruitment end date
31/12/2019
Locations
Countries of recruitment
Finland
Trial participating centre
Helsinki University Central Hospital (HUCH) Womens Hospital
Helsinki
00610
Finland
Sponsor information
Organisation
Helsinki University Central Hospital
Sponsor details
Kätilöopiston Sairaala
Sofianlehdonkatu 5 A
Helsinki
00029 HUS
Finland
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Not defined
Funder name
Helsingin ja Uudenmaan Sairaanhoitopiiri
Alternative name(s)
Helsinki University Central Hospital, HUS
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
Finland
Funder name
Helsingin Yliopisto
Alternative name(s)
University of Helsinki, Helsingfors Universitet
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
Finland
Results and Publications
Publication and dissemination plan
1. Planned methods publication 2016-2017.
2. Planned other publications 2017-2019.
Intention to publish date
01/01/2017
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary