The association between preterm birth, vaginal microbiome, immune defence and HPV among women with cervical precancer

ISRCTN	ISRCTN17063005
DOI	https://doi.org/10.1186/ISRCTN17063005
Secondary identifying numbers	N/A

Submission date: 15/09/2015
Registration date: 22/03/2016
Last edited: 04/01/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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 2023

Who is funding the study?
Helsinki University Central Hospital

Who is the main contact?
Dr Pekka Nieminen

Contact information

Dr Pekka Nieminen
Scientific

Kätilöopiston Sairaala
Sofianlehdonkatu 5 A
Helsinki
00029 HUS
Finland

Study information

Study design	Observational single-center study
Primary study design	Observational
Secondary study design
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	The association between preterm birth, vaginal microbiome, immune defence and HPV among women with cervical precancer: an observational single-center study
Study acronym	MI-HPV
Study objectives	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(s)	University of Helsinki Institutional Review Board, 30/01/2014, ref: 21/13/03/2014
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	17/09/2015
Completion date	31/12/2023

Eligibility

Participant type(s)	Mixed
Age group	Adult
Sex	Female
Target number of participants	50+50+50
Key inclusion criteria	Healthy volunteers and colposcopy patients.
Key exclusion criteria	1. Pregnancy 2. Vaginal bleeding 3. Previous cervical surgery
Date of first enrolment	17/09/2015
Date of final enrolment	31/12/2019

Locations

Countries of recruitment

Finland

Study participating centre

Helsinki University Central Hospital (HUCH) Womens Hospital

Helsinki
00610
Finland

Sponsor information

Helsinki University Central Hospital
Hospital/treatment centre

Kätilöopiston Sairaala
Sofianlehdonkatu 5 A
Helsinki
00029 HUS
Finland

Website	http://www.hus.fi
"ROR"	https://ror.org/02e8hzf44

Funders

Funder type

Not defined

Helsingin ja Uudenmaan Sairaanhoitopiiri
Government organisation / Local government

Alternative name(s): Helsinki University Central Hospital, HUS
Location: Finland

Helsingin Yliopisto
Government organisation / Universities (academic only)

Alternative name(s): University of Helsinki, Helsingfors Universitet, Universitas Helsingiensis, HY, UH
Location: Finland

Results and Publications

Intention to publish date	31/12/2024
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	1. Planned methods publication 2016-2017. 2. Planned other publications 2017-2019.
IPD sharing plan	Not provided at time of registration

Editorial Notes

04/01/2023: The following changes were made to the trial record:
1. The intention to publish date was changed from 01/01/2017 to 31/12/2024.
2. The overall end date was changed from 31/12/2020 to 31/12/2023.
3. The plain English summary was updated to reflect these changes.