Vulvar HSILPhase 4VulVaccinNCT06052696
Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL
A Phase 4 study testing Gardasil 9 Suspension for Injection in people with Vulvar HSIL and HPV, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Vulvar HSIL, HPV
- What is being tested?
- Gardasil 9 Suspension for Injection
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2024to 1 Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women 18 years or older
- Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
- Planned for treatment (surgical, laser or imiquimod) for vHSIL
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC
Rotterdam
R. van de Laar, +3110 704 0704, vulvaccin@erasmusmc.nl
About this study
Official title: Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL, a Randomised Placebo Controlled Trial
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.
Read more
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
- Being tested
- Gardasil 9 Suspension for Injection, Placebo
- Keywords
- HPV, VHSIL, Vaccination
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gardasil 9 Suspension for InjectionDrug
After randomisation in the Gardasil arm, women will receive 3 Gardasil vaccinations
- 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.
- Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection.
- Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.
PlaceboDrug
After randomisation in the PLacebo arm, women will receive 3 Placebo vaccination with NaCl 0.9%
- 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.
- Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection.
- Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.
| Study group | Role | What they receive |
|---|---|---|
| Gardasil 9 | Experimental | see intervention Receives: Drug: Gardasil 9 Suspension for Injection |
| placebo | Placebo comparator | see intervention Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo?
Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months
Measured: 24 months after last inclusion
Secondary outcomes (11)
1. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months?
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months
Measured: 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?
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months for primary vHSIL versus recurrent vHSIL.
Measured: 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?
- Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between the different treatment modalities
Measured: 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?
- Difference in number and percentage for additional treatment necessary after primary treatment.
Measured: 24 months after last inclusion
5. What is the effect of vaccination versus placebo on different HPV types (HPV type of primary and recurrence)?
- Description and percentage of different HPV types. Percentage clearance of primary HPV type for vaccination versus placebo.
Measured: 24 months after last inclusion
6. What is the level of antibodies at baseline and after (placebo) vaccination?
- Number of antibodies and percentage of increase or decrease after vaccination compared to antibodies before vaccination. Is there correlation between number or percentage of recurrence. Is that different in primary versus recurrent episode vHSIL
Measured: 24 months after last inclusion
7. Is the intervention cost effective?
- incremental cost-effectiveness ratio (ICER), described the difference in costs and budget impact analysis
Measured: 24 months after last inclusion
8. Is Quality of life (measured with Euroqol 5D-5L questionnaire) improved after vaccination compared to placebo?
8.Description and change in numeric value and percentage in different score form questionnaires. Percentage increase of decrease QoL
Measured: 24 months after last inclusion
8. Is sexual health (measured with Female Sexual Function Index, FSFI questionnaire) improved after vaccination compared to placebo?
8.Description and change in numeric value and percentage in different score form questionnaires. Percentage increase of decrease sexual impact
Measured: 24 months after last inclusion
9. What is the effect of vaccination versus placebo on CIN/cervical cytology of the uterine cervix?
- Difference number and percentage in HPV types cervical cytology and vHSIL before and after vaccination.
Measured: 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)?
- Difference in number and percentage in recurrence rate of vulvar HSIL and vulvar cancer between HPV vaccination and placebo. Other HPV related disease known?
Measured: 5 and 10 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2023
- Study start1 Mar 2024
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vulvar HSILStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society
- Responsible party
- Principal investigator, Ralf van de Laar, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06052696
- Sponsor's protocol ID
- MEC-2023-0526
- Other IDs
- 2023-506792-94-00, 2023
- Acronym
- VulVaccin
- Status last verified
- Aug 2026
- First submitted
- 31 Aug 2023
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 40394508
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL, a Randomised Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT06052696
- Acronym / sponsor ID
- VulVaccin / MEC-2023-0526
- Conditions
- Vulvar HSIL, HPV
- Keywords
- HPV, VHSIL, Vaccination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Cancer Society
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 25 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gardasil 9 | Experimental | Drug: Gardasil 9 Suspension for Injectionsee intervention |
| placebo | Placebo comparator | Drug: Placebosee intervention |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Women 18 years or older
- Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
- Planned for treatment (surgical, laser or imiquimod) for vHSIL
Key exclusion criteria (6 listed)
- Prior HPV vaccination
- (Micro-) invasive carcinoma or history of HPV related genital carcinoma (cervix, anal, vulva)
- Pregnancy
- Women allergic to vaccine components
- HIV infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gardasil 9 Suspension for InjectionAfter 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 | Gardasil 9 |
| PlaceboAfter 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. | Drug | placebo |
Primary outcome
Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo?
Time frame: 24 months after last inclusion
Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months
11 secondary outcomes
1. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months?
Time frame: 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?
Time frame: 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?
Time frame: 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?
Time frame: 24 months after last inclusion
5. What is the effect of vaccination versus placebo on different HPV types (HPV type of primary and recurrence)?
Time frame: 24 months after last inclusion
6. What is the level of antibodies at baseline and after (placebo) vaccination?
Time frame: 24 months after last inclusion
7. Is the intervention cost effective?
Time frame: 24 months after last inclusion
8. Is Quality of life (measured with Euroqol 5D-5L questionnaire) improved after vaccination compared to placebo?
Time frame: 24 months after last inclusion
8. Is sexual health (measured with Female Sexual Function Index, FSFI questionnaire) improved after vaccination compared to placebo?
Time frame: 24 months after last inclusion
9. What is the effect of vaccination versus placebo on CIN/cervical cytology of the uterine cervix?
Time frame: 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)?
Time frame: 5 and 10 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Derived from this study: PubMed 40394508Vaessen 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.
- Individual participant dataSharing planned: Undecided
Related trials for Vulvar HSIL
Not yet recruitingPhase 1
Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV
Human Papilloma Virus, Human Immunodeficiency Virus
Not yet recruitingPhase 3
Trial to Evaluate Nonavalent HPV Vaccine as a Secondary Prevention in Patients Treated for Human Papilloma Virus Related High-grade Squamous Intraepithelial Lesions
Patients With Primary HPV High-grade Squamous Intra-epithelial Lesions (HSIL) at Vulvar Site, Patients With Primary HPV High-grade Squamous Intra-epithelial Lesions (HSIL) at Vaginal Site
RecruitingPhase 2
Phase II Study of Artesunate Ointment for the Treatment of Vulvar High Grade Squamous Intraepithelial Lesions (Vulvar HSIL, VIN2/3)
Vulvar Diseases, HPV Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gardasil 9 Suspension for Injection in people with Vulvar HSIL and HPV, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo? (time frame: 24 months after last inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06052696, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.