Multiple Human Papillomavirus Infections in the Development of CIN

NCT06862102 | Recruiting DMC FDA Drug

• 1 other identifier: HPV-dysplasia
• Study Type: observational
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CIN - Cervical Intraepithelial Neoplasia; HPV; HPV Vaccines

Outcome Measures

Primary Outcomes (1)

• effect of HPV vaccination on multiple HPV infection

  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 Outcomes (1)

• progression to CIN2+ in vaccinated group

  2 years

Study Arms (2)

CIN1 with multiple HPV genotypes infection underwent vaccination

Biological: HPV vaccine

CIN1+ with multiple HPV genotypes infection not underwent vaccination

Interventions

HPV vaccine BIOLOGICAL

vaccine administration

CIN1 with multiple HPV genotypes infection underwent vaccination

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with HPV infection and abnormal citology attending colposcopy

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo, SC Ostetricia e Ginecologia 1

Pavia, Pavia, 27100, Italy

RECRUITING

Related Publications (2)

• Ghelardi A, Parazzini F, Martella F, Pieralli A, Bay P, Tonetti A, Svelato A, Bertacca G, Lombardi S, Joura EA. SPERANZA project: HPV vaccination after treatment for CIN2. Gynecol Oncol. 2018 Nov;151(2):229-234. doi: 10.1016/j.ygyno.2018.08.033. Epub 2018 Sep 6. No abstract available.

  PMID: 30197061 BACKGROUND

• Spinillo A, Gardella B, Roccio M, Alberizzi P, Cesari S, Patrizia M, Silini E. Multiple human papillomavirus infection with or without type 16 and risk of cervical intraepithelial neoplasia among women with cervical cytological abnormalities. Cancer Causes Control. 2014 Dec;25(12):1669-76. doi: 10.1007/s10552-014-0471-6. Epub 2014 Oct 9.

  PMID: 25296710 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

cervical stripping

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Papillomavirus Vaccines

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Central Study Contacts

Barbara Gardella, Principal investigator

CONTACT

+390382503720; b.gardella@smatteo.pv.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 1, 2025
• First Posted: March 6, 2025
• Study Start: January 8, 2021
• Primary Completion: February 28, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

IT (1)