Faster Elimination of HPV Infection and Cervical Cancer Using Concomitant HPV Vaccination and HPV Screening: A Demonstration Project in Rwanda

NCT06536855 | Not Yet Recruiting Phase 4

• 1 other identifier: FasterHPV01
• Study Type: interventional
• Target: 100,000
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Prevalence of HPV infections in the study participants

  To evaluate whether organised, concomitant HPV vaccination and HPV screening offered to women aged 23-29 will result in faster elimination of HPV infection in the study districts in Rwanda, using before-design modeling the expected numbers after the intervention. Overall and type-specific prevalence and incidence of HPV will be obtained from the HPV screening at 2 years. Observed numbers will be compared to the predicted (expected numbers).

  24 months

Secondary Outcomes (1)

• 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.

  24 months

Study Arms (1)

Gardasil 9 Arm

EXPERIMENTAL

The study is open label with only one arm that will receive the vaccine

Biological: Gardasil 9

Interventions

Gardasil 9 BIOLOGICAL

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11. GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

Also known as: HPV/DNA testing (Gynotyping)

Gardasil 9 Arm

Eligibility Criteria

• Age: 23 Years - 29 Years
• Gender Eligibility Details: Females are the only ones concerned by Cervical cancer
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rwanda Biomedical Centre: lead
• Merck Sharp & Dohme LLC: collaborator
• Karolinska Institutet: collaborator
• Center for Family Health Research/Projet San Francisco: collaborator
• ELEKTA Foundation: collaborator

Related Publications (19)

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Related Links

• Globocan estimate, Rwanda 2020
• IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 90
• WHO guideline for screening and treatment of cervical precancer lesions for cervical cancer prevention
• Global strategy to accelerate the elimination of cervical cancer as a public health problem
• Human papillomavirus vaccines: WHO position paper (2022 update)

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Human Papillomavirus Recombinant Vaccine nonavalent

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Francois Uwinkindi, MD, Msc Epi

  Rwanda Biomedical Centre

  PRINCIPAL INVESTIGATOR

• Claude Mambo Muvunyi, MD, PhD

  Rwanda Biomedical Centre

  STUDY CHAIR

• Joachim Dillner, MD, PhD

  Karolinska Institutet

  STUDY DIRECTOR

Central Study Contacts

Francois Uwinkindi, MD, Msc Epi

CONTACT

+250788854473; francois.uwinkindi@rbc.gov.rw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 5, 2024
• Study Start: September 1, 2024
• Primary Completion: March 30, 2025
• Study Completion: March 30, 2026
• Last Updated: August 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share