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

NCT ID: NCT06536855

Last Updated: 2024-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

100000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-01

Study Completion Date

2026-03-30

Brief Summary

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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.

Detailed Description

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Conditions

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Cervical Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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 Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Gardasil 9 Arm

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

Group Type EXPERIMENTAL

Gardasil 9

Intervention Type 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.

Interventions

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Gardasil 9

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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HPV/DNA testing (Gynotyping)

Eligibility Criteria

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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
Minimum Eligible Age

23 Years

Maximum Eligible Age

29 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

Center for Family Health Research/Projet San Francisco

UNKNOWN

Sponsor Role collaborator

ELEKTA Foundation

UNKNOWN

Sponsor Role collaborator

Rwanda Biomedical Centre

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francois Uwinkindi, MD, Msc Epi

Role: PRINCIPAL_INVESTIGATOR

Rwanda Biomedical Centre

Claude Mambo Muvunyi, MD, PhD

Role: STUDY_CHAIR

Rwanda Biomedical Centre

Joachim Dillner, MD, PhD

Role: STUDY_DIRECTOR

Karolinska Institutet

Central Contacts

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Francois Uwinkindi, MD, Msc Epi

Role: CONTACT

+250788854473

References

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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

Reference Type RESULT
PMID: 33538338 (View on PubMed)

Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002 Apr;55(4):244-65. doi: 10.1136/jcp.55.4.244.

Reference Type RESULT
PMID: 11919208 (View on PubMed)

Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, Clifford GM. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012 Nov 15;131(10):2349-59. doi: 10.1002/ijc.27485. Epub 2012 Mar 20.

Reference Type RESULT
PMID: 22323075 (View on PubMed)

Denny L, Adewole I, Anorlu R, Dreyer G, Moodley M, Smith T, Snyman L, Wiredu E, Molijn A, Quint W, Ramakrishnan G, Schmidt J. Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa. Int J Cancer. 2014 Mar 15;134(6):1389-98. doi: 10.1002/ijc.28425. Epub 2013 Nov 14.

Reference Type RESULT
PMID: 23929250 (View on PubMed)

Carrillo-Garcia A, Ponce-de-Leon-Rosales S, Cantu-de-Leon D, Fragoso-Ontiveros V, Martinez-Ramirez I, Orozco-Colin A, Mohar A, Lizano M. Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer. Gynecol Oncol. 2014 Sep;134(3):534-9. doi: 10.1016/j.ygyno.2014.06.018. Epub 2014 Jun 27.

Reference Type RESULT
PMID: 24979052 (View on PubMed)

Cheng L, Wang Y, Du J. Human Papillomavirus Vaccines: An Updated Review. Vaccines (Basel). 2020 Jul 16;8(3):391. doi: 10.3390/vaccines8030391.

Reference Type RESULT
PMID: 32708759 (View on PubMed)

Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, Berkhof J, Peto J, Meijer CJ; International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014 Feb 8;383(9916):524-32. doi: 10.1016/S0140-6736(13)62218-7. Epub 2013 Nov 3.

Reference Type RESULT
PMID: 24192252 (View on PubMed)

Knaul FM, Farmer PE, Krakauer EL, De Lima L, Bhadelia A, Jiang Kwete X, Arreola-Ornelas H, Gomez-Dantes O, Rodriguez NM, Alleyne GAO, Connor SR, Hunter DJ, Lohman D, Radbruch L, Del Rocio Saenz Madrigal M, Atun R, Foley KM, Frenk J, Jamison DT, Rajagopal MR; Lancet Commission on Palliative Care and Pain Relief Study Group. Alleviating the access abyss in palliative care and pain relief-an imperative of universal health coverage: the Lancet Commission report. Lancet. 2018 Apr 7;391(10128):1391-1454. doi: 10.1016/S0140-6736(17)32513-8. Epub 2017 Oct 12. No abstract available.

Reference Type RESULT
PMID: 29032993 (View on PubMed)

Binagwaho A, Wagner CM, Gatera M, Karema C, Nutt CT, Ngabo F. Achieving high coverage in Rwanda's national human papillomavirus vaccination programme. Bull World Health Organ. 2012 Aug 1;90(8):623-8. doi: 10.2471/BLT.11.097253. Epub 2012 May 23.

Reference Type RESULT
PMID: 22893746 (View on PubMed)

Gatera M, Bhatt S, Ngabo F, Utamuliza M, Sibomana H, Karema C, Mugeni C, Nutt CT, Nsanzimana S, Wagner CM, Binagwaho A. Successive introduction of four new vaccines in Rwanda: High coverage and rapid scale up of Rwanda's expanded immunization program from 2009 to 2013. Vaccine. 2016 Jun 17;34(29):3420-6. doi: 10.1016/j.vaccine.2015.11.076. Epub 2015 Dec 17.

Reference Type RESULT
PMID: 26704259 (View on PubMed)

Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine. 2012 Nov 20;30 Suppl 5(0 5):F123-38. doi: 10.1016/j.vaccine.2012.04.108.

Reference Type RESULT
PMID: 23199956 (View on PubMed)

Bogaards JA, Coupe VM, Meijer CJ, Berkhof J. The clinical benefit and cost-effectiveness of human papillomavirus vaccination for adult women in the Netherlands. Vaccine. 2011 Nov 8;29(48):8929-36. doi: 10.1016/j.vaccine.2011.09.055. Epub 2011 Sep 22.

Reference Type RESULT
PMID: 21945961 (View on PubMed)

Lei J, Ploner A, Elfstrom KM, Wang J, Roth A, Fang F, Sundstrom K, Dillner J, Sparen P. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020 Oct 1;383(14):1340-1348. doi: 10.1056/NEJMoa1917338.

Reference Type RESULT
PMID: 32997908 (View on PubMed)

Karimi-Zarchi M, Allahqoli L, Nehmati A, Kashi AM, Taghipour-Zahir S, Alkatout I. Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial. BMC Public Health. 2020 Feb 27;20(1):274. doi: 10.1186/s12889-020-8371-z.

Reference Type RESULT
PMID: 32106837 (View on PubMed)

Castellsague X, Munoz N, Pitisuttithum P, Ferris D, Monsonego J, Ault K, Luna J, Myers E, Mallary S, Bautista OM, Bryan J, Vuocolo S, Haupt RM, Saah A. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age. Br J Cancer. 2011 Jun 28;105(1):28-37. doi: 10.1038/bjc.2011.185. Epub 2011 May 31.

Reference Type RESULT
PMID: 21629249 (View on PubMed)

Skinner SR, Szarewski A, Romanowski B, Garland SM, Lazcano-Ponce E, Salmeron J, Del Rosario-Raymundo MR, Verheijen RH, Quek SC, da Silva DP, Kitchener H, Fong KL, Bouchard C, Money DM, Ilancheran A, Cruickshank ME, Levin MJ, Chatterjee A, Stapleton JT, Martens M, Quint W, David MP, Meric D, Hardt K, Descamps D, Geeraerts B, Struyf F, Dubin G; VIVIANE Study Group. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet. 2014 Dec 20;384(9961):2213-27. doi: 10.1016/S0140-6736(14)60920-X. Epub 2014 Sep 1.

Reference Type RESULT
PMID: 25189358 (View on PubMed)

Ibrahim Khalil A, Zhang L, Muwonge R, Sauvaget C, Basu P. Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials. BMJ Open. 2023 Oct 24;13(10):e069616. doi: 10.1136/bmjopen-2022-069616.

Reference Type RESULT
PMID: 37879679 (View on PubMed)

Sayinzoga F, Umulisa MC, Sibomana H, Tenet V, Baussano I, Clifford GM. Human papillomavirus vaccine coverage in Rwanda: A population-level analysis by birth cohort. Vaccine. 2020 May 19;38(24):4001-4005. doi: 10.1016/j.vaccine.2020.04.021. Epub 2020 Apr 24.

Reference Type RESULT
PMID: 32336599 (View on PubMed)

Lehtinen M, Baussano I, Paavonen J, Vanska S, Dillner J. Eradication of human papillomavirus and elimination of HPV-related diseases - scientific basis for global public health policies. Expert Rev Vaccines. 2019 Feb;18(2):153-160. doi: 10.1080/14760584.2019.1568876. Epub 2019 Feb 7.

Reference Type RESULT
PMID: 30657348 (View on PubMed)

Related Links

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https://www.who.int/publications/i/item/9789240030824

WHO guideline for screening and treatment of cervical precancer lesions for cervical cancer prevention

https://www.who.int/publications/i/item/9789240014107

Global strategy to accelerate the elimination of cervical cancer as a public health problem

Other Identifiers

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FasterHPV01

Identifier Type: -

Identifier Source: org_study_id

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