Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL

Официальное название

Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL, a Randomised Placebo Controlled Trial

Обзор

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.

Вмешательства

• Препарат 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 a
• Препарат 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 a

Первичные конечные точки

• Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo? [Срок оценки: 24 months after last inclusion]

Вторичные конечные точки (11)

• 1. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months? [Срок оценки: 6 and 12 months after last inclusion]
• 2. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months in primary episode vHSIL versus recurrence? [Срок оценки: 6 and 12 months after last inclusion]
• 3. What is the effectiveness of adjuvant vaccination in different treatments of vHSIL (laser, imiquimod, excision) at 24 months? [Срок оценки: 24 months after last inclusion]
• 4. How often is additional treatment for vHSIL needed in the study period? Is this different between the study groups? [Срок оценки: 24 months after last inclusion]
• 5. What is the effect of vaccination versus placebo on different HPV types (HPV type of primary and recurrence)? [Срок оценки: 24 months after last inclusion]
• 6. What is the level of antibodies at baseline and after (placebo) vaccination? [Срок оценки: 24 months after last inclusion]
• 7. Is the intervention cost effective? [Срок оценки: 24 months after last inclusion]
• 8. Is Quality of life (measured with Euroqol 5D-5L questionnaire) improved after vaccination compared to placebo? [Срок оценки: 24 months after last inclusion]
• 8. Is sexual health (measured with Female Sexual Function Index, FSFI questionnaire) improved after vaccination compared to placebo? [Срок оценки: 24 months after last inclusion]
• 9. What is the effect of vaccination versus placebo on CIN/cervical cytology of the uterine cervix? [Срок оценки: 24 months after last inclusion]
• 10. Long-term follow-up: Is there a difference between vaccination and placebo group in number of recurrences of vHSIL (5 and 10 years) and the occurrence of vulvar malignancies (2, 5 and 10 years)? [Срок оценки: 5 and 10 year]

Критерии участия

Критерии включения

• Women 18 years or older
• Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
• Planned for treatment (surgical, laser or imiquimod) for vHSIL

Критерии исключения

• Prior HPV vaccination
• (Micro-) invasive carcinoma or history of HPV related genital carcinoma (cervix, anal, vulva)
• Pregnancy
• Women allergic to vaccine components
• HIV infection
• Immune compromised patients (currently on immunosuppressive medication

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Нидерланды · 1 центр

• Erasmus MC — Rotterdam

Публикации

• Vaessen VJGM, van de Laar RLO, Piso-Jozwiak M, Dalm VASH, Joura EA, Jentschke M, van Beekhuizen HJ. Adjuvant nonavalent HPV vaccination in women treated for vulvar HSIL, a randomized placebo-controlled trial; VulVaccin study protocol. BMC Cancer. 2025 May 20;25(1):903. doi: 10.1186/s12885-025-14275-w. PMID 40394508

Идентификаторы

NCT: NCT06052696 · MEC-2023-0526 · 2023-506792-94-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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