Clinical Trial Evaluating Secondary HPV Vaccination After Treatment of High-grade Cervical Lesions (HPV2)

Phase 2 Clinical Trial Evaluating Secondary HPV Vaccination After Treatment of High-grade Cervical Lesions (HPV2-2303)

This is a single-center, Phase II interventional study evaluating secondary HPV vaccination after treatment of high-grade cervical lesions. The study aims to estimate the rate of HPV clearance within two years following an initial positive HPV control test in women over 45 years of age who are chronic HPV carriers and have undergone treatment for high-grade intraepithelial cervical lesions, and who receive HPV vaccination.

The study includes two cohorts:

1. Eligible patients who consent to vaccination will participate in a prospective, single-center, single-arm, interventional clinical trial (Category 2).
2. Non-vaccinated patients will be included in a non-interventional observational study, with no changes to their standard care.

Study Overview

• Status: Recruiting
• Conditions: Cervical Lesion
• Intervention / Treatment: Biological: Human Papillomavirus 9-valent Vaccine, Recombinant

Detailed Description

The aim of this study is to estimate the proportion of HPV clearance within two years following an initial positive HPV control test in women over 45 years old who are chronic HPV carriers and have undergone treatment for high-grade intraepithelial cervical lesions. These women will receive HPV vaccination as part of the study.

Other objectives of the study include:

1. Describing the dynamics of viral clearance in chronic HPV carriers who receive HPV vaccination.
2. Evaluating the safety of HPV vaccination.
3. Estimating the incidence of recurrence of high-grade intraepithelial cervical lesions in chronic HPV carriers after surgical treatment of the initial lesion and HPV vaccination.
4. Estimating the incidence of invasive gynecological cancers (cervical, vaginal, or vulvar) in chronic HPV carriers after surgical treatment of the initial lesion and HPV vaccination.
5. Identifying factors associated with the refusal of HPV vaccination, such as smoking, parity, body mass index, employment status, education level, family history, and marital status.

6. Describing compliance with the proposed vaccination schedule in terms of:

   1. Number of injections completed.
   2. Adherence to the timing of injections.

7. Evaluating the effect of vaccination on:

   1. HPV clearance within two years.
   2. The dynamics of viral clearance.
   3. The risk of recurrence of high-grade intraepithelial lesions.
   4. The risk of developing invasive gynecological cancers (cervical, vaginal, or vulvar).

by comparing vaccinated patients included in the clinical trial with the cohort of non-vaccinated patients (those who refused HPV vaccination or for other reasons).

• Study Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Emilie HEYMAN-DECOUPIGNY; Phone Number: 0320295918; Email: promotion@o-lambret.fr
• Study Contact Backup: Name: Hugo JOSE; Phone Number: 0320295918; Email: promotion@o-lambret.fr

Study Locations

• France
  • Lille, France, 59020
    • Recruiting
    • Centre Oscar Lambret
    • Contact: Nora ALLOY, MD; Phone Number: 0320295959; Email: n-alloy@o-lambret.fr
    • Sub-Investigator: Carlos MARTINEZ GOMEZ, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Common eligibility criteria for the study (for both cohorts) :

   1. Female patient over 45 years old
   2. Patient treated by conization for high-grade cervical epithelial lesion
   3. Positive HPV test at the 6-month post-operative control (a delay of 6 to 12 months will be accepted), leading to an indication for a control colposcopy (+/- biopsy) according to standard surveillance practices.
   4. N.B. : Patients with abnormalities at the initial control colposcopy and/or positive biopsy remain eligible for the study, whether vaccinated or not.

2. Additional eligibility criteria for the clinical trial (Vaccinated patients cohort)

   1. No contraindication to HPV vaccination with Gardasil 9
   2. Patient consented to HPV vaccination with Gardasil 9
   3. Affiliated with a social security system
   4. Informed and signed written consent provided
   5. N.B. : Patients infected with HIV are eligible for the vaccine trial provided they are on antiretroviral therapy.

3. Inclusion criteria for the data study (Non-vaccinated patients cohort)

   1. Patient eligible for the study (a) and not eligible for the clinical trial (b) due to:

      • refusal of vaccination, or
      • A contraindication to vaccination
   2. No objection to the use of their personal data for research purposes

N.B. : A patient who initially refused vaccination may later request to be vaccinated as part of the trial after signing the consent form. The vaccine trial analysis will include all patients who started vaccination within 6 months after the initial HPV control test.

Exclusion Criteria:

1. Common exclusion criteria for the study (for both cohorts)

   1. History of primary HPV vaccination
   2. History of HPV-induced invasive cancer (cervical, vaginal, vulvar, anal, oropharyngeal cancer)

2. Exclusion criteria for the clinical trial (Vaccinated patients cohort)

   1. Patient refusing HPV vaccination
   2. Patient with a contraindication to HPV vaccination with Gardasil 9
   3. Patient deprived of liberty or under guardianship
3. Exclusion criteria for the data study (Non-vaccinated patients cohort) a) Opposition to the use of their personal data for research purposes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccinated patients; Human papillomavirus vaccine, nonvalent, Gardasil 9	Biological: Human Papillomavirus 9-valent Vaccine, Recombinant; HPV vaccine administered in three doses: first dose on day 1, second dose 2 months later, and third dose 4 months after the second dose, within a one-year period.; Other Names: Gardasil 9
No Intervention: Non-vaccinated patients; no changes to standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of HPV-negative status	The primary outcome is to estimate the proportion of HPV-negativation status within two years of the initial positive HPV control test. Negativation is defined as a negative HPV test result. If the patient cannot be evaluated due to the occurrence of cancer, this will be considered a failure (equivalent to absence of negativation).	Within 2 years after the initial HPV control test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamics of HPV viral clearance	HPV status over time assessed by smear every 12 months until HPV-negative status (in the study: within 5 years of follow-up). When the test is negative, a follow-up smear is performed three years later (in the study: within 5 years of follow-up)	every 12 months for up to 5 years
Adverse Events	Adverse events will be recorded and evaluated according to the NCI-CTCAE V5.0 scale. AEs will be documented after each vaccination, during subsequent injections, and through a follow-up phone call 30 days after the third injection. Severe Adverse Events (grade ≥3) will be considered significant.	Throughout the vaccination schedule plus 30 days
Incidence of high-grade intraepithelial lesions	The time to recurrence of high-grade cervical lesions will be calculated from the date of the initial HPV control test to the first documented event of lesion recurrence, as indicated by clinical follow-up and diagnostic testing.	From the initial HPV control test up to the first recurrence event up to 5 years
Incidence of invasive gynecological cancer	The incidence of invasive gynecological cancers (cervix, vagina, vulva) will be determined by calculating the time from the initial HPV control test to the first occurrence of HPV-related invasive cancer at any sites (cervix, vagina, vulva)	From the initial HPV control test to the occurrence of invasive cancer up to 5 years
Compliance with vaccination schedule	Compliance will be measured by the number of vaccine doses received and adherence to the recommended timing between injections, including the interval between the 1st and 3rd doses of Gardasil 9.	Throughout the vaccination period (up to 1 year)

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: Canceropôle Nord Ouest
• Investigators: Study Director: Nora ALLOY, MD, Centre Oscar Lambret

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: October 22, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: oncology; vaccination; HPV; secondary prevention; cervix
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Neoplasms; Human Papillomavirus Recombinant Vaccine nonavalent
• Other Study ID Numbers: HPV2-2303; 2024-513081-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No