Clinical trial NCT06536855: Faster Elimination of HPV Infection and Cervical Cancer Using Concomitant HPV Vaccination and HPV Screening: A Demonstration Project in Rwanda
Official title: Faster Elimination of HPV Infection and Cervical Cancer Using Concomitant HPV Vaccination and HPV Screening: A Demonstration Project in Rwanda
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Cervical Cancer
Lead sponsor: Rwanda Biomedical Centre
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Karolinska Institutet
name: Center for Family Health Research/Projet San Francisco
name: ELEKTA Foundation
First posted: 2024-08-05
Enrollment: 100000
Sex: FEMALE
Minimum age (years): 23
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: At the first visit we will administer Gardasil 9 to women aged 23 to 29 years and screening them for HPV to get baseline information, after 24 months at the second visit, provide the second dose and screen again for HPV to be able to compare HPV prevalence at baseline and 24 months after administering the second dose of vaccine.
Primary purpose: PREVENTION

Brief summary: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Rwanda is among countries with a high burden cervical cancer, with an annual incidence of 28.2/100,000 women (1,229 new cases in 2020) and a mortality rate of 20.1/100,000 (829 deaths in 2018) according to WHO (IARC 2020).

Cervical cancer is almost completely preventable because of the highly effective primary (HPV vaccine) and secondary (HPV screening) prevention measures. However, these measures have not been equitably implemented across and within LMICs countries.

Given the current situation, where the screening coverage is still low due to financial and operational challenges, it will take many years to achieve the elimination targets as included in the global elimination strategy. We are proposing to implement an innovative strategy to accelerate the elimination of cervical cancer in Rwanda consisting of concomitant HPV vaccination and HPV screening for young women aged 23-29 years old.

HPV screening and vaccination are complementary preventive options often implemented as separate public health programs. This project proposal aims to address this disconnect by combining both strategies with the ultimate purpose of accelerating the reduction of cervical cancer incidence and mortality in Rwanda and making the programs both cost-effective and sustainable.

Primary objective

The study aims to evaluate whether organized, concomitant HPV vaccination and HPV screening offered to girls and women aged 23-29 years will result in more rapid elimination of HPV infections in the target districts in Rwanda.

The study design is a before-after study design of the intervention, where the projected incidences and prevalence at the 2-year follow-up visit are modeled using the data from the baseline visit, with evaluation using Observed/expected numbers.

Secondary objectives

The study will evaluate whether concomitant vaccination and cervical screening result in an improved efficiency and/or safety of the cervical cancer screening program. These objectives will be examined among women who participated in the combined screening and vaccination study.

i) Protection of Gardasil 9 against HPV infection and against CIN2+ by Gardasil 9 HPV vaccine types in 23 to 29-year-old women from the study districts. This analysis will be performed every 2 years, and the first analysis will determine the effectiveness of one-dose vaccination (incident infections of HPV vaccine types at 2 years), whereas all subsequent analysis will determine the effect of 2-dose vaccinations. The study will be powered to detect a decline in invasive cervical cancer among the study participants, using the cervical cancer incidence in the surrounding districts of Rwanda as the reference.

ii) Efficiency will also be measured by the yield of histopathologically confirmed high-grade cervical cancer precursors or cancer (cervical intraepithelial neoplasia grade 2, 3, or cervical cancer) in relation to the consumption of resources and convenience for the women, using the yield at the baseline visit (10% of women tested) as the comparator. The hypothesis is that 2 years after vaccination, there will be only a few incident infections (only some old, persistent infections) resulting in high PPV and high yield of CIN2+ at modest consumption of resources.

End of the study

One screening interval (2 years) after the last visit of the last subject, defined as the day the last study subject receives her second vaccination.

The study will be implemented in 4 districts of Rwanda covering 100,000 women aged 23 to 29 years old. We will use Gardasil 9, the HPV the second generation HPV Vaccine manufactured by Merck.


Eligibility criteria: Inclusion Criteria:

Eligible women will include women within the age range of 23-29, who have not opted out of the screening program and who consent to participate in the study

Exclusion Criteria:

* Known history of severe allergic reaction or hypersensitivity to any of the components of the HPV vaccine. (For GARDASIL 9: Amorphous aluminium hydroxyphosphate sulphate adjuvant, Sodium chloride, L-histidine, Polysorbate 80, or Sodium borate)
* Known history of immune-related disorders
* Current acute severe febrile illness, except for minor infections such as a cold, mild upper respiratory infection, or low-grade fever.
* Administration of immunoglobulin or blood-derived products within 6 months prior to the scheduled HPV vaccine first dose
* Current pregnancy (reported)
* Women with a total hysterectomy

Primary outcomes:
measure: Prevalence of HPV infections in the study participants
timeFrame: 24 months
Secondary outcomes:
measure: Prevalence of histopathologically confirmed high-grade cervical cancer precursors or cancer (cervical intraepithelial neoplasia grade 2, 3, or cervical cancer) (CIN2+) by HPV type in the lesion.
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Rwanda Biomedical Centre
name: Francois Uwinkindi, MD, Msc Epi
role: PRINCIPAL_INVESTIGATOR
affiliation: Rwanda Biomedical Centre
name: Claude Mambo Muvunyi, MD, PhD
role: STUDY_CHAIR
affiliation: Karolinska Institutet
name: Joachim Dillner, MD, PhD
role: STUDY_DIRECTOR
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