A Phase 4 interventional study of Nonavalent HPV vaccine (9vHPV/Gardasil-9™). in Cervical Intraepithelial Neoplasia Grade I/ II/ III (CIN I/II/III), Human Papillomavirus (HPV) Infections and High-risk HPV, sponsored by Miquel Angel Pavon Ribas. Recruiting at 1 site in Spain. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-23.
Sponsored by Miquel Angel Pavon Ribas · Phase 4, Interventional, and Prevention
This is a non-randomized, open label study to assess the reduction of Human Papillomavirus (HPV) infectivity and transmission in women positive for HPV16 and/or 18 in a cervical, oral and anal sample and vaccinated with 9vHPV/Gardasil-9™.
The primary objective of the study is to demonstrate that vaccination with a 3-dose regimen of 9vHPV will reduce viral infectivity in HPV 16/18/16+18-positive women. This objective rests upon the hypothesis that, since vaccination with 9vHPV triggers the production of type-specific HPV antibodies which are exudated to the cervical and other infected mucosae, these antibodies adhere to and neutralize newly produced HPV 16/18 viral particles also present in the mucosae, thus reducing HPV's infective capacity and transmission to sexual partners.
Secondary objectives of the study are:
The main endpoint of the study is the evaluation of the HPV infective capacity in cervical, anal and oral samples from HPV 16, 18 or 16+18-positive women, using a cellular assay that models in-vitro the cervical mucosa. In brief, the specific HPV biomarker E1\^E4 is measured in HaCaT keratinocytes after being cultured with study samples and thus, exposed to HPV16/18 viral particles. A reduction in E1\^E4 expression is expected for keratinocytes exposed to samples taken after vaccination with 9vHPV, since the specific HPV antibodies also present in these samples would bind HPV viral particles and prevent infection of cultured keratinocytes.
Other endpoints included in the study are:
A minimum of 39 and 30 women will be enrolled in two different study population cohorts, respectively:
Candidates to participate in the study are selected according to the HPV DNA test result in a cervical sample taken in their routine cervical cancer screening visit or in their routine gynaecological follow-up visit.
There is no control group in this study: all participants are expected to complete all the per-protocol procedures in a total of 4 study visits within an average of 7 months' duration: Visit 1/ Day1, Visit 2/Month 2, Visit 3/Month 6, and Visit 4/Month 7.
The study procedures are the following:
Regarding data analysis for primary objective assessment, differences in the infectivity rate before (Day 1/ Visit 1) and after vaccination with 3 doses of 9vHPV (Month 7/ Visit 4) will be compared in cervical, anal and oral samples using non-parametric Wilcoxon signed rank test. The same assessment will be done in 1- or 2-dose vaccination scenario.
Antibody production before and after vaccination will be summarized for each of the 9vHPV-covered HPV types.
have no apparent cervical lesion (Cohort 1). have a CIN1/2 lesion which is eligible for conservative treatment (cohort 1). have HPV 16 and/or HPV 18 positive anal test with non-apparent anal lesions or with anal lesions eligible for conservative treatment (Cohort 2).
have HPV 16 and/or HPV 18 positive cervical test with vulvar premalignant lesion or condylomas, associated to HPV infection (Cohort 2).
Exclusion Criteria:
Single arm, vaccination with 9vHPV in a 3-dose regimen (Day 1, Month 2, Month 6).
Biological: Nonavalent HPV vaccine (9vHPV/Gardasil-9™).
Sterile suspension, 0.5 ml dose, intramuscular administration in a 3 dose-regimen (Day 1, Month 2, Month 6), prepared from the highly purified virus-like particles (VLPs) of the major capsid L1 protein from 9 HPV types: 6/11/16/18/31/33/45/52/58. 9vHPV is currently indicated in the EU in individuals from 9 years of age for the prevention of diseases caused by vaccine's 9 HPV types: genital warts (HPV6 and 11) and premalignant lesions and cancers affecting the cervix, vulva, vagina and anus (HPV16, 18, 31, 22, 45, 52 and 58). It was authorized for marketing in the EU on June 9th, 2015.
To demonstrate that vaccination with a 3-dose regimen of 9vHPV will change viral infectivity in cervical, anal and oral samples from HPV 16/18/16+18-positive women.
In-vitro infectivity evaluation of cervical, anal, and oral samples collected before and after 9vHPV vaccination, by expression of E1\^E4 HPV biomarker in HaCaT keratinocytes.
Time frame: 7 month
Detection of HPV 6/11/16/18/31/33/45/52/58 L1 antibodies in cervical, anal and oral samples collected before and after 9vHPV vaccination, using ELISA and cLIA.
This endpoint will allow to associate the reduction in viral infectivity with the presence of neutralizing antibodies.
Time frame: 7 month
HPV16/18 virion detection in cervical, anal and oral samples collected before and after 9vHPV vaccination.
HPV16/18 virion detection will be carried out using ELISA and electronic microscopy in cervical, anal and oral samples collected before and after 9vHPV vaccination.
Time frame: 7 month
HPV DNA detection in cervical, anal and oral samples collected before and after 9vHPV vaccination.
HPV DNA detection will be performed using Anyplex HPV28 in cervical, anal and oral samples collected before and after 9vHPV vaccination.
Time frame: 7 month
HPV DNA genotyping in cervical, anal and oral samples collected before and after 9vHPV vaccination.
HPV DNA genotyping will be performed using Anyplex HPV28 in cervical, anal and oral samples collected before and after 9vHPV vaccination.
Time frame: 7 month
To determine HPV antibody titration before and after vaccination for each of the 9vHPV-covered HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58).
To determine HPV 6/11/16/18/31/33/45/52/58 L1 antibody titration in serum samples collected before and after 9vHPV vaccination, using ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, using cLIA for all 9vHPV-covered types except 16 and 18, in samples from RIFT-HPV 1 study cohort.
Time frame: 7 month
To demonstrate viral infectivity change in cervical, oral and anal samples from HPV 16/18/16+18-positive women after vaccination with 1-dose or 2-dose regimen of 9vHPV.
In-vitro infectivity evaluation of cervical, anal, and oral samples collected before and after 9vHPV vaccination with 1st dose and 2nd dose, by expression of E1\^E4 HPV biomarker in HaCaT keratinocytes.
Time frame: 7 month
Plan to share: No
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