Multiple Human Papillomavirus Infections in the Development of CIN (HPV dysplasia)

March 6, 2025 updated by: Barbara Gardella, Fondazione IRCCS Policlinico San Matteo di Pavia

Prospective Clinical Study on the Role of Multiple Human Papillomavirus Infections in Lower Genital Tract Dysplasias and Its Interactions with HPV Vaccination

Multiple infections of high-risk genotypes of Human Papillomavirus (HR-HPV) in patients with abnormal cervical cytological or histological findings are detectable in a percentage ranging from 20% to 50% of cases.

Some studies have detected a certain tendency to specific clustering in multiple infections, both inter-species and inter-genotypic, such as HPV 31-35-56, HPV 16-51-52, HPV 16-18, HPV 51-52. Furthermore, a greater tendency of the HPV16 genotype to cluster with genotypes of different species is reported in the literature. However, other studies claim a random character of such genotypic associations in multiple infections. This heterogeneity of results of the studies present in the literature underlies multiple factors, both epidemiological and methodological, implicated in the high variability of prevalence and diagnostic findings of multiple infections. In particular, with regard to epidemiological characteristics, factors influencing the distribution of multiple infections appear to be the origin and type of population, economic-social status, young age, HIV seropositivity and recent sexual activity. A further hypothesized element is represented by a possible individual susceptibility dictated by the immune profile of the host towards specific genotypes, potentially facilitating the occurrence of co-infections by these, possibly resulting in a synergistic effect on the oncogenic potential. From a clinical point of view, to date multiple cross-sectional studies suggest an association between multiple infections of HR-HPVs and an increased risk of high-grade cervical dysplasia. In particular, a proportional relationship is observed between the number of genotypes present and the severity of the lesion. Furthermore, it has been reported that the correlation between multiple HR-HPV infections and severe cervical dysplasia CIN2+ is significant both in the presence and absence of the known oncogenic genotype HPV16, assuming a possible synergistic interaction between specific high-risk genotypes. However, other studies seem to refute the clinical relevance of multiple infections in the risk of neoplastic progression of cervical lesions, mostly claiming the precept of "one virus, one lesion", such that each dysplastic lesion is associated with the action of a distinct HR-HPV genotype. In this assumption, therefore, it is argued that moderate-severe cervical dysplasias are due to the action of a single oncogenic genotype, predominantly HPV16, while the presence of other HR-HPVs is attributable to transient infections, mostly represented by mild dysplasias (CIN1). As far as biological knowledge is concerned, in vitro studies currently demonstrate how it is possible for a single cell to be co-infected by at least two HR-HPV genotypes and how this can result in peculiar inter-genotypic molecular interactions that influence the replication cycle and the respective capacity for cellular persistence and transformation of the individual genotypes involved. The inter-genotypic competition mechanisms detected, therefore, occur mostly during the initial phases of acute infection by the HR-HPVs involved. However, it has been demonstrated that when a persistent infection of a genotype has already been established, this is no longer able to negatively interact with a subsequent incident infection by a different HR-HPV genotype. This finding in the biological field is consistent with the clinical correlate according to which the association between multiple HR-HPV infections and the risk of high-grade cervical dysplasia is greater when these are established on a pre-existing persistent infection. Therefore, it is conceivable that there is a higher rate of genotype-specific association in multiple HR-HPV infections found in cervical dysplastic lesions, defined by the peculiar capacities of the individual genotypes to give rise to persistent cellular infections. Despite the proven efficacy of vaccination programs in preventing cervical dysplastic lesions and infection by the main viral genotypes with high oncogenic risk, numerous studies demonstrate the clinical efficacy of HPV vaccination also in reducing the rate of disease recurrence in patients undergoing excisional treatment. A first explanatory hypothesis of this phenomenon is represented by the protection that the vaccination procedure would provide to those patients not previously infected by the target HR-HPV genotypes, potentially causative of de novo infections with high oncogenic risk. A further hypothesis under study is represented by the fact that the administration of the HPV vaccine following excisional treatment would prevent the reduction of the immune response against HPV.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

152

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo, SC Ostetricia e Ginecologia 1
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

patients with HPV infection and abnormal citology attending colposcopy

Description

Inclusion Criteria:

  • Pap smear cytology suggestive of dysplastic cervical lesion worthy of colposcopic evaluation and HPV test
  • HPV-related vaginal and/or vulvar lesion
  • patients with histological diagnosis after biopsy of Cervical Intraepithelial Neoplasia (CIN) or invasive cervical cancer of stage lower than FIGO staging 1B.

Exclusion Criteria:

  • pregnancy
  • age less than 18 years
  • previous treatment for HPV-related vaginal, vulvar or cervical lesion in the previous 5 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
CIN1 with multiple HPV genotypes infection underwent vaccination
Biological: HPV vaccine
vaccine administration
CIN1+ with multiple HPV genotypes infection not underwent vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
effect of HPV vaccination on multiple HPV infection
Time Frame: 2 years
To evaluate the effect of multiple HPV infections on the risk of regression, persistence or progression to CIN2/3 after 24 months from biopsy for CIN1+ in relation to the execution of HPV vaccine.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression to CIN2+ in vaccinated group
Time Frame: 2 years
To compare the progression of cervical dysplasia in the population vaccinated with the anti-HPV vaccine 9 within the unvaccinated population at 2 years after excisional treatment for CIN2+ Progression is given by persistence (within 6 months) or recurrence (12 months or more).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2021

Primary Completion (Estimated)

February 28, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

March 1, 2025

First Submitted That Met QC Criteria

March 1, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 6, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HPV-dysplasia

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

at the end of the study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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