ERADICATING CERVICAL CANCER IN KENYA (MISP 60403)

Study Overview
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Brief Summary
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We propose a study of a strategy designed to 1) increase cervical cancer screening using a community-based approach, and 2) determine the efficacy of HPV vaccination in a region of Kenya where half of all children are chronically exposed to aflatoxin.

Detailed Description
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Cervical cancer is caused by oncogenic HPV, and is the main cause of cancer-related death among Kenyan women [1-3]. This malignancy is preventable through a combination of screening of adult women and vaccination of children and adolescents against HPV infection. However, only 5% of Kenyan women are regularly screened, and only 14% have ever been screened, which in Kenya is done by a method known as Visual Inspection with Acetic Acid (VIA) [3, 4]. Obstacles to screening include travel to clinics, costs, poor specificity of VIA, lack of trained personnel, and others. In addition, while safe and effective HPV vaccines have been available for 15 years, very few (<1%) Kenyan children and adolescents have been vaccinated [5, 6]. Obstacles to vaccination include costs, delivery infrastructure, lack of education, travel to clinics, and others. In addition, there are few studies of HPV vaccination in African children, and two-dose regimens may not provide adequate protective antibody levels among children chronically exposed to aflatoxin, a potent immunosuppressive agent found in contaminated corn. We propose a study of a strategy designed to 1) increase cervical cancer screening using a community-based approach, and 2) determine the efficacy of HPV vaccination in a region of Kenya where half of all children are chronically exposed to aflatoxin. Objective 1 (Cervical cancer screening): Evaluate High-Risk (HR)-HPV DNA testing of self-collected vaginal swabs as a triage step for VIA among rural Kenyan women. Hypothesis: All women with negative HR-HPV DNA tests will have normal VIA examinations or falsely-abnormal VIA examinations based on cervical biopsy results. Our rationale is that if this hypothesis is correctly proven, it will suggest that VIA is unnecessary for women with negative HR-HPV DNA tests in self-collected vaginal swabs. Objective 2 (HPV vaccination): Determine the effects of chronic aflatoxin exposure among Kenyan children/adolescents on the likelihood of seroconversion to HPV types represented in the HPV vaccine. Hypothesis: Compared to children/adolescents without detectable plasma aflatoxin, children/adolescents with evidence of chronic aflatoxin exposure will have a reduced likelihood of seroconversion to HPV types represented in the HPV vaccine. Our rationale is that if this hypothesis is correctly proven, it will suggest that adjustments in vaccination doses/schedules may be needed for children with chronic exposure to aflatoxin to assure adequate protection against HPV infection.

Official Title
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ERADICATING CERVICAL CANCER IN KENYA: Benefits of Community-based Prevention, and the Effects of Aflatoxin on HPV Vaccination

Conditions
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Human Papilloma Virus, HIV Infections

Intervention / Treatment
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* Biological: HPV vaccine, Merck


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kenyan women between ages of 18 and 60 years and children/grandchildren aged 9 through 18 of women attending the Community Meetings. Exclusion Criteria: Pregnancy, history of cervical cancer, allergy to HPV vaccine (children) -

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Children of mothers in the study will receive the HPV vaccine as per Kenya guidelines.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV vaccination<br>Children receiving HPV vaccine will be studies for seroconversion to HPV types, and aflatoxin levels in blood will be measured and compared to seroconversion. | Biological: HPV vaccine, Merck<br>* We will offer vaccination against HPV to 900 children/grandchildren aged 9 through 18 of women attending the Community Meetings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of high-grade cervical intraepithelial neoplasia (CIN) 2/3+ | We will report the rate and relative risk of biopsy-proven VIA abnormality between women with positive HR-HPV and women with negative HR-HPV. | Two years | 
| Seroconversion to all HPV vaccine types | We will report the rate and relative risk of seroconversion to all HPV types combined and to each of the nine HPV types represented in the nine-valent HPV vaccine between children with and without plasma aflatoxin detection. | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, HIV, Kenya