Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL

Summary

Problem description:

Yearly, approximately 45000 women develop vulvar cancer worldwide. It is estimated that about 30% of all vulvar carcinomas are HPV related. As with other HPV related (pre)malignancies, the incidence has been rising over the past 20 years. The peak incidence of premalignant lesions of the vulva, also called Vulvar High Grade Squamous Intraepithelial Lesion (vHSIL), lies between 35 and 40 years of age. Multiple treatments are available, including surgery, laser vaporization, and topical imiquimod, with comparable success rate. Despite treatment, at least 30% of women will develop a recurrence within 2 years, with a much higher lifetime risk of recurrence. This results in multiple treatments with sometimes disfiguring effects and associated negative psychosocial and psychosexual impact. Woman with vulvar HSIL have a lifelong increased risk of vulvar cancer, and approximately 10% of women with (treated) vulvar HSIL will develop vulvar cancer within 10 years of first diagnosis. The risk of malignancy is significantly higher in women with recurrent disease, compared to women without recurrence.

Solution / research direction, To date, a successful strategy for reduction of recurrences of HSIL has not been established. The available positive evidence on the use of concurrent HPV vaccination in the treatment of vulvar HSIL is rising, yet insufficient to guide clinical practice. There is limited data that prophylactic HPV vaccination after treatment of vulvar HSIL reduces the chance of recurrence, therefore leading to a reduction in repeated (surgical) interventions. There are no randomised controlled studies supporting this data.

Aim The aim of current project is to determine the effectiveness of nonavalent HPV vaccination versus placebo in preventing recurrence in women treated for vulvar HSIL.

Plan of investigation This is a randomised, double blinded, placebo controlled trial in women treated for vulvar HSIL. Adult female patients, diagnosed with vulvar HSIL planned for treatment and no prior HPV vaccination will be included. Randomisation will be in a 1:1 ratio to additional nonavalent HPV vaccination versus additional placebo vaccination.

Expected outcome. Based on previous non-randomised studies, a significant reduction in recurrences, improvement of quality of life and a reduction of economic burden of the disease is expected.

Conditions

• Vulvar HSIL
• HPV

Interventions

DRUG

Gardasil 9 Suspension for Injection

After randomisation in the Gardasil arm, women will receive 3 Gardasil vaccinations 1. First injection: preferable at time of start treatment (imiquimod, lase or surgery). Window 4 weeks prior to treatment start (because surgical treatment can be postponed for logistical reasons) and 4 weeks after start treatment. 2. Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection. 3. Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.

DRUG

Placebo

After randomisation in the PLacebo arm, women will receive 3 Placebo vaccination with NaCl 0.9% 1. First injection: preferable at time of start treatment (imiquimod, lase or surgery). Window 4 weeks prior to treatment start (because surgical treatment can be postponed for logistical reasons) and 4 weeks after start treatment. 2. Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection. 3. Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.

Sponsors & Collaborators

• Dutch Cancer Society

  collaborator OTHER

• Erasmus Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-01

Primary Completion

2028-12-01

Completion

2030-12-01

Countries

• Netherlands

Study Locations