The Mother-Daughter Project: a Project to Improve Cervical Cancer Screening and Vaccination Against HPV in Western Kenya
- Registration Number
- NCT07240220
- Lead Sponsor
- Indiana University
- Brief Summary
* Although cervical cancer is preventable, this malignancy is the main cause of cancer-related deaths among Kenyan women, especially in those living in rural areas, where screening is seldom performed, and girls are not vaccinated against HPV, the cause of cervical cancer.
* Obstacles to screening include long travel to clinics, high costs, and factors related to the screening method used in sub-Saharan Africa.
* In addition, while safe and effective HPV vaccines have been available since 2006, very few (\<5%) Kenyan girls have been vaccinated, in spite of school-based programs that function in some parts of Kenya. Obstacles to vaccination include high costs, poor delivery infrastructure, lack of education, long travel to clinics, and others.
* We began a community-based program in 2018 to develop a framework for eradication of cervical cancer by effective screening of adult women and vaccinating female children.
* This initiative, known as the Kenya Mother-Daughter Cervical Cancer Eradication Project, or the Mother-Daughter Project (MDP) is highly acceptable in the Webuye region of Western Kenya based on the data-driven evidence obtained from previous feasibility studies funded by Merck.
* We propose to enroll a cohort of 500 adult women in community meetings as part of the MDP. This will strengthen the power of our analysis on HR-HPV testing in detecting premalignant cervical lesions, especially in HIV-infected women. We will evaluate improvement of knowledge and attitude in women regarding cervical cancer screening and HPV vaccination before and after participating the MDP community meeting.
* We will identify families who were invited to the MDP but declined to participate. We will investigate and identify barriers leading to their non-participation in the MDP.
* We will encourage the non-participants to participate in MDP by in-person home visit by a MDP counselor.
* We will examine factors including aflatoxin and nutritional status associated with the short and longer-term immune responses to HPV vaccination among 9- to 14-year-old rural Kenyan girls. We propose to enroll and vaccinate an additional 2000 girls.
- Detailed Description
Study Title:
The Mother-Daughter Project: inclusion of difficult-to-reach Kenyan families, and studies of factors influencing the immune response to HPV vaccination (MISP-4)
Request Date: July 10, 2023 Institution Name Indiana University School of Medicine (USA) and Moi University (Kenya)
Investigator Contact Information:
* Full address
* Phone No.
* Fax No.
* e-mail address Darron R. Brown, MD, MPH Department of Medicine, Division of Infectious Diseases VanNuys Medical Sciences Building, Suite 224 635 Indiana University School of Medicine, Indianapolis, IN 46202, USA
1-317-407-9034 1-317-274-8115 (fax) darbrow@iu.edu
Section #2- Core Protocol
2.1 Objectives \& Hypotheses
Cervical cancer is caused by oncogenic, or "high-risk" (HR) human papillomavirus (HPV) and is the main cause of cancer-related death among Kenyan women \[1-3\]. Although preventable, this malignancy occurs frequently in women living in rural areas of Kenya where screening is seldom performed, and girls are not vaccinated against HPV. Only 5% of Kenyan women are regularly screened, and 14% have ever been screened, done in Kenya by a method known as Visual Inspection with Acetic Acid (VIA) \[3, 4\]. Obstacles to effective screening include long travel to clinics, high costs, and factors related to VIA such as poor sensitivity and specificity, the need for practitioner training for VIA, variability among providers in VIA interpretation, and others. In addition, while safe and effective HPV vaccines have been available since 2006, very few (\<5%) Kenyan girls have been vaccinated \[5, 6\]. Obstacles to vaccination include high costs, poor delivery infrastructure, lack of education, long travel to clinics, and others. We began a community-based program in 2018 to develop a framework for eradication of cervical cancer by effective screening of adult women and vaccinating female children.
This initiative, known as the Kenya Mother-Daughter Cervical Cancer Eradication Project, or the Mother-Daughter Project (MDP), is highly acceptable in the Webuye region of Western Kenya based on the data-driven evidence obtained from the two previous feasibility studies \[7\]. Our first two proposals demonstrated that greater than 90% of invited women who attended community meetings found this method of screening acceptable. We propose a continuation of the MDP that will allow us to accumulate additional data, solidify the overall project and answer additional research questions. We propose to enroll an additional cohort of 500 adult women and strengthen the power of our analysis on HR-HPV testing in detecting premalignant lesions of the cervix, especially in HIV-infected women. Second, we will identify families who were invited to the MDP but declined to participate. We will investigate and identify barriers leading to their non-participation of the MDP. Third, we will examine factors associated with the immune response to HPV vaccination among 9- to 14-year-old rural Kenyan girls. We propose to enroll and vaccinate an additional 2000 girls.
We will accomplish the following specific aims in this proposed study:
Objective 1. Determine if High-Risk (HR)-HPV DNA testing of self-collected vaginal swabs has greater sensitivity in detection of cervical intraepithelial lesion grades 2 and 3, or invasive cancer (CIN2/3+) compared to VIA.
Hypothesis: Regardless of HIV status, HR-HPV DNA tests of self-collected vaginal swabs will have greater sensitivity in detection of high-grade dysplasia than VIA, using cervical biopsy results as the gold standard.
Objective 2. Determine benefits and barriers to MDP participation using survey tools and interviews to assess knowledge and attitudes toward cervical cancer screening and prevention.
Hypothesis 1: Women will have an improved knowledge towards cervical cancer screening and HPV vaccination and a more positive attitude towards their own health and the health of their daughter(s) after participating in the MDP.
Hypothesis 2: We will be able to identify women who were invited but decline to participate in the MDP and identify barriers of non-participation by interviewing these women.
Hypothesis 3. More than half of the non-participating women will agree to participate in the MDP following the in-person interview with the MDP counselor.
Objective 3. Identify factors that influence short- and longer-term immunity to the 9v HPV vaccine in rural Kenyan girls.
Hypothesis: Specific factors including aflatoxin exposure, poor nutritional status, and others can be identified among 9- to 14-year-old girls that are associated with lower rate of seroconversion and lower antibody titers measured approximately 18 to 24 months after receiving the 9v HPV vaccine.
2.2 Background \& Rationale, Significance of Selected Topic \& Preliminary Data Project Framework
The basic framework for the MDP was established in 2018 and has been modified based on the experiences of the past five years. This framework combines screening of adult women (ages 25 through 49) using HPV DNA testing of self-vaginal swabs and HPV vaccination of daughters (ages 9 through 14) of mothers attending the community meetings.
Rationale for conducting the proposed study
Strategies based on centralized care have been unsuccessful in preventing cervical cancer in Kenyan women. HR-HPV DNA testing of self-collected vaginal swabs is acceptable and feasible, and we have now shown that such testing can occur in a community setting in rural Kenya; other groups have demonstrated similar successes in Africa \[4, 8, 9\]. We have shown that most women invited to community meetings attend the meetings and most women agree to enroll in the studies, receive education about cervical cancer, and provide a self-collected vaginal swab for HR-HPV DNA testing. Nearly all women who attended the community meetings were willing to have their female children vaccinated against HPV. We have also shown that HPV vaccine can be delivered to western Kenya and can be administered to girls in a community setting. We wish to continue to use this to further study the utility of this strategy and to address research questions that will elucidate the barriers to participation and will begin to provide information about the impact of the program.
The reasons we want to enroll an additional 500 adult women are as follows. First, we need to strengthen the power of our analysis on HR-HPV testing in detecting premalignant lesions of the cervix, especially in HIV-infected women. Second, we want to continue our studies of the acceptability of the community-based program and define the obstacles of the program among women who are newly enrolled. We will ask women to fill out related to these issues. Third, we will identify families who were invited to the MDP but declined to participate. We will investigate and identify barriers leading to their non-participation of the MDP. Fourth, although we expected to be able to address the issue of sensitivity and specificity of HR-HPV testing compared to VIA in the first MISP (MISP-1), we noted an unexpectedly low rate of abnormal VIA in the original cohorts, which reduced our power to compare testing methods. Thus, additional women need to be enrolled to address this important question. Fourth, this program has benefited the community by providing a cancer prevention program that includes HPV vaccination, to which they have previously not had access to. This program has engendered trust between the local population and caregivers. Lastly, we hope to apply to the Gates Foundation or another agency for a larger award of several years' duration, based on as much preliminary data as can be generated from this project.
The same rationale applies to our desire to vaccinate additional girls via the MISP mechanism. We have vaccinated 900 girls to date as part of the second MISP (MISP-2); we plan to vaccinate 2000 girls for MISP-3. For MISP-4, we will examine factors associated with the 24-month immune response to HPV vaccination among 9- to 14-year-old rural Kenyan girls. We propose to enroll and vaccinate an additional 2000 girls. Because aflatoxin exposure represents a potential public health problem that could thwart efforts to control HPV-associated malignancies, we will study the immunological response to vaccination in girls with chronic aflatoxin exposure, once they have completed the vaccine regimen. In addition, other nutritional factors may have an impact on the immunological response to vaccination, we will study several factors as indicated below in Study Procedures.
Thus, these aims build on the infrastructure we have created in the first two award cycles. We believe the MDP, a community-based approach to cervical cancer utilizing HPV DNA-based screening can become the standard for western Kenya, act as a framework for HPV-associated cancer control and can lead to a significant improvement in patient care as well as providing an opportunity for hypothesis driven research.
2.3 Study Design This prospective cohort study will be conducted in Webuye, a community located in the western region of Kenya, in Bungoma County on the highway to Uganda. The total population of Webuye sub-county is approximately 25,000. A "Community Entry Strategy" was utilized to introduce our prior studies and to invite women to community meetings. We trained a female Kenyan Counselor about cervical cancer (including the cause and the ways to prevent the cancer), how to educate women about this malignancy and how to instruct women in performance of self-collected swabs. Village chiefs, village elders, women deemed to be community leaders, and leaders of the local churches have been approached by the Counselor and Study Coordinator to discuss the goals, strategy, and risks and benefits of the study; this process will be repeated before the current study is initiated. Discussions have focused on the importance of early screening for cervical cancer, the use of self-collected swabs for screening, and the importance of vaccination of children against HPV.
Inclusion Criteria: Kenyan women ages 25 through 49 years who are able/willing to sign informed consent and willing to participate in the community meetings. Kenyan girls, ages 9 through 14 whose mothers are able/willing to sign informed consent to be vaccinated and who can return for the second HPV vaccine dose in 6 to 12 months.
Exclusion Criteria: Kenyan women who are pregnant or are not able/willing to sign informed consent. Girls who are not willing or unable to return for the second HPV vaccine dose.
Ethical approval will be obtained from the Institutional Review Board of Indiana University School of Medicine and the review boards at Moi Teaching Referral Hospital (MTRH), Moi University, Eldoret, Kenya, and the Kenya National Commission for Science Technology and Innovation (NACOSTI). Written informed consent will be obtained from all adult participants, and all women will be given a written copy of the signed consent in either English or Swahili. Assent will be obtained from the participating girls before enrollment.
For Aim 1 (Determine if High-Risk (HR)-HPV DNA testing of self-collected vaginal swabs has greater sensitivity in detection of CIN2/3 compared to VIA), we plan to enroll 500 Kenyan women between the ages of 25 to 49 years (the government-recommended age range for screening in Kenya). Only women who did not participate in our prior studies will be enrolled. Women will be instructed in collecting vaginal swabs during the community meetings, and these self-collected swabs will be given to the Counselor. Swabs will be tested for HR-HPV DNA at Lancet Laboratories in Nairobi (or at Moi University if reagents can be obtained) using the Roche Cobas Assay. All women will be asked to travel to the Webuye Clinic for pelvic examination and VIA (the Kenyan standard of care). Cervical biopsy will be performed on all HIV-infected women and on those HIV-uninfected women with abnormal VIA examinations. Results will be analyzed as described below to determine the sensitivity, specificity, positive predictive value, and negative predictive value for HR-HPV DNA to predict biopsy-proven CIN2/3 in the HIV-infected group of women.
For Aim 2 (Determine benefits and barriers to MDP participation using survey tools and interviews to assess knowledges and attitudes toward cervical cancer screening and prevention), adult women and their daughters (if they have daughters), will be asked to fill out questionnaires that will provide data about educational aspects and overall acceptability of the MDP and obstacles related to its initiation. This will be done following the second vaccine dose that will be administered to girls at community meetings. Women in the Webuye community have been satisfied with self-collection of swabs as a method of cervical cancer screening, and most are willing to have their daughters vaccination against HPV. However, it is important to identify those women who do not want to attend meetings, do not want to provide self-collected swabs, or do not want their daughters vaccinated against HPV infection. We will be able to trace these women through 1) records that will be acquired for all women who attend the community meeting, 2) records about women who refuse to participate, and 3) meeting in person (home visits) with women who decline through their phone contacts, through community leaders who understand their physical locations.
For Aim 3 (Identify factors that influence immunity to the 9v HPV vaccine in rural Kenyan girls), we will enroll 2000 girls, ages 9 through 14 and administer the 9v HPV vaccine to these girls at community meetings. We will study factors associated with the immunological response to the 9v HPV vaccine; 120 girls will have a blood sample taken at a community meeting, approximately 12 months after receiving the second 9v HPV vaccine dose. Each girl's BMI will be determined. The blood sample will be analyzed for antibody titers to each of the nine HPV types represented in the 9v vaccine, and for folate, iron, and hemoglobin. In addition, girls will be interviewed with their mothers regarding specific dietary habits.
2.5 Study Procedures Study procedures for the Mother Daughter Project (MDP)
Community meetings and self-collected vaginal swabs
The Counselor will invite local women ages 25 through 49 years and their 9 through 14-year-old daughters/grand-daughters to meetings in Webuye. These meetings have been very successful. Approximately 30 to 40 women attend each meeting, and many women bring their daughters (and granddaughters). The instructional brochure developed by Dr. Victoria Champion and her colleagues at Indiana University School of Nursing for the proper self-collection method (available in both English and Swahili) will again be shared with participants. Women will obtain the swab in a private setting at the meeting. Self-collected swabs will be gathered by the Counselor, then a delivery person will transport the swabs (dry, no added medium) at ambient temperature to Moi Teaching and Referral Hospital (MTRH) laboratories in Eldoret, Kenya (about 60 km away), or to the Lancet Laboratory in Nairobi.
Swabs will be tested for HR-HPV DNA using the Roche Cobas Assay, a test that provides specific HPV 16 or 18 detection as well as detection of any of 12 additional oncogenic types (HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). Results of the Cobas Assay will be entered into a RedCap database that we have previously created. Results of the Cobas Assay will be delivered electronically to the Counselor's tablet, who will discuss these results with women at subsequent community meetings.
VIA and cervical biopsy
All women will be asked to go to the Webuye Clinic for VIA (the current standard of care for cervical cancer screening in Kenya) (Figure 1, above). All HIV-infected women will undergo cervical biopsy regardless of VIA results, because of the low sensitivity of VIA in these women. HIV-uninfected women with an abnormal VIA will undergo punch biopsy of the cervix (two sites). Women with abnormal VIA examinations will then be treated according to established local algorithms. In the event of suspected cancer, the participant will be sent to the Gynecologic Cancer Clinic at MTRH. The flow of adult participants and clinical specimens is shown in Figure 3 below. The numbers shown represent estimates of disease prevalence and outcomes based on our experience from the first two periods of funding.
The total number of specimens collected for the study include:
1. Roche Cobas Assays: 500
2. Cervical biopsies: estimated 101
3. Serum samples to test for antibodies against the 9 types represented in the 9v HPV vaccine, and for folate, iron, and hemoglobin: 120
4. Plasma for aflatoxin testing: 120
In our vision for the future, women will be triaged to the local clinic for further evaluation only if they have a positive HR-HPV test in the Cobas Assay, taking advantage of the high (\>99%) negative predictive value of the this assay previously established in studies of HIV-uninfected women in the U.S.A., where the test is now FDA-approved for primary cervical cancer screening \[10-12\]. However, the Roche Cobas Assay has not been adequately tested in HIV-infected women living in any country, or in HIV-uninfected women living in sub-Saharan Africa utilizing self-collected vaginal swabs.
Follow-up visits for cervical cancer screening
Women will be asked to return to the Webuye Clinic for cervical cancer screening in one year if HIV-infected or in three years if HIV-uninfected.
HPV vaccination of girls
Women will be provided information at the community meetings on the purpose, efficacy, safety, and potential adverse effects of HPV vaccination. Vaccination against HPV will be offered to girls (2000 in all) ages 9 through 14 of women attending the community meetings. The second dose of the HPV vaccine will be administered six to twelve months after the first dose at subsequent community meetings. Careful records will be kept, and all families will be given a record of the vaccine administration. This is especially important because Kenya began a facility-based HPV vaccine program for 10-year-old girls in 2019, but few girls have been vaccinated to date. Our approach is important because many girls will not be able to attend school to receive the vaccine or do not have the means to travel to local facilities for vaccination. It is therefore important that community-based opportunities for vaccination are an option in Kenya. In addition, the government program vaccinates girls at age 10 and does not include 9-year-olds or girls ages 11 through 14, so our project will be important for these girls.
Questionaries
A questionnaire will be administered at the end of the study. This questionnaire was developed for a previous version of the MDP (in Swahili and English) and will be used to capture the opinions of mothers and daughters regarding all aspects of the program. Mothers will be asked about the self-collected swabs, travel to community meetings and the Clinic, and acceptability of HPV vaccination of daughters. Non-participant women to MDP will be located and interviewed by the MDP counselor in person to determine the reasons that these women did not participate.
2.6 Study Duration The aims of this project will be accomplished during a two-year period. Key personnel will be trained in the first three months of the project. The remainder of the first year, and the second year will be devoted to community meetings, vaccinations, and VIA examinations, biopsies, treatments, follow up visits, and data analysis.
2.7 Statistical Analysis and Sample Size Justification Sample size consideration and analysis plan for Objective 1: Determine if High-Risk (HR)-HPV DNA testing of self-collected vaginal swabs has greater sensitivity in detection of CIN2/3 compared to VIA.
Hypothesis: Regardless of HIV status, HR-HPV DNA tests of self-collected vaginal swabs will have greater sensitivity in detection of CIN2/3 than VIA, using cervical biopsy results as the gold standard.
Sample size consideration: We will enroll 500 adult women in this study. HR-HPV DNA testing results and VIA results will be available for 500 women, and the cervical biopsy results will be available for an estimated 101 women (83 HIV-infected women, and 18 HIV-uninfected women with abnormal VIA). These 101 women will have a complete data set (HR-HPV result, VIA result, and cervical biopsy result). Of these 101 women, we expect that 47 women will have a positive HR-HPV DNA test and 54 will have a negative HR-HPV DNA test, based on data from our prior research in the Webuye region) (Figure 4). Of the 47 women with positive HR-HPV DNA tests, 33 women are expected to be HIV-infected and 14 HIV-uninfected. In addition, based on data from a study conducted by our team in Kenya \[manuscript under review\], we expect 8 biopsy-proven CIN2/3 detection to be found in the HR-HPV positive/HIV-infected women (24% of 33=8 women), and 1 biopsy-proven CIN2/3 detection in the HR-HPV positive/HIV-uninfected women (1 of 14 women). As a result, we expect 9 biopsy-proven CIN2/3 to be detected in 47 women with positive HR-HPV DNA tests. Of the 54 women with a negative HR-HPV DNA test, we expect 50 women to be HIV-infected and 4 women HIV-uninfected. We expect that 2 biopsy-proven CIN2/3 will be detected in the HR-HPV negative/HIV-infected women (2 of 50 women), and zero biopsy-proven CIN2/3+ detection in the HR-HPV negative/HIV-uninfected women (Figure 4). Therefore, we estimate the sensitivity of the HR-HPV DNA tests of self-collected vaginal swabs to be 82% in detection of CIN2/3 in Kenya women.
Of these 101 women, we expect 20 women will have an abnormal VIA and 81 women will have a normal VIA. Of the 20 women with abnormal VIA, we expect 2 women to be HIV-infected and 18 to be HIV-uninfected. Based on data from MISP-1 and MISP-2, we expect biopsy-proven CIN2/3 will be detected in 2 (10%) women with an abnormal VIA (1 HIV-infected woman and 1 HIV-uninfected woman). Of the 81 women with normal VIA, all will be HIV-infected. Based on our prior studies, we expect that CIN2/3 cases will be detected in 9 HIV-infected women with normal VIA (Figure 5). Therefore, we expect the sensitivity of VIA to be poor (18%) in detection of CIN2/3 in this cohort of Kenya women.
Our sample size of 101 women having results of HR-HPV DNA test, VIA and cervical biopsy will provide 81.6% power to detect a 0.64 (64%) difference of sensitivity between HR-HPV DNA test and VIA in detection of CIN2/3 at a two-sided 0.05 significance level based on the McNamar's test. The above calculation is made based on the assumption that the prevalence of CIN2/3 is 11% (11 CIN2/3 cases among 101 women) in this cohort of Kenya women, and the disagreement of CIN2/3 detection between HR-HPV DNA test and VIA occurs among 65% of the sample.
Data analysis plan. We will report the rates of HR-HPV DNA positivity and VIA abnormality for all enrolled women (500 women) and stratify by HIV status. For the cohort of women who will undergo cervical biopsy (101 women), we will report the rates of HR-HPV positivity, VIA abnormality and CIN2/3 detection for all women and by HIV status. We will calculate sensitivity and 95% confidence intervals (95%CIs) of HR-HPV and VIA in detection of biopsy-proven CIN2/3. Comparison in sensitivity between HR-HPV and VIA will be performed using McNemar's test, and the difference in sensitivity and 95%CIs will be reported. In addition, we will calculate specificity, positive predict value (PPV), negative predict value (NPV), and 95%CIs of HR-HPV and VIA in detection of biopsy-proven CIN2/3. We will also perform McNemar's tests to compare the specificity, PPV, NPV between HR-DNA tests and VIA in detection of biopsy-proven CIN2/3. In addition, we will compare AUCs of the ROC between HR-HPV DNA testing and VIA. Additional analyses will be conducted separately among HIV-infected and HIV-uninfected women.
Sample size consideration and analysis plan for Objective 2: Determine benefits and barriers to MDP participation using survey tools and interviews to assess knowledges and attitudes toward cervical cancer screening and prevention.
Hypothesis 1: Women will have an improved knowledge towards cervical cancer screening and HPV vaccination and a more positive attitude towards their own health and the health of their daughter(s) after participating in the MDP.
We will evaluate women's knowledge of cervical cancer screening and HPV vaccination and attitudes towards their own health and health of their daughters(s) before and after the MDP community meeting.
Sample size consideration: We will assess women's knowledge of cervical cancer screening and HPV vaccination and women's attitude towards their own health and health of their daughters(s) before and after a MDP community meeting using questionnaires. We expect that ≥95% of women will have an improved knowledge level of cervical cancer screening and HPV vaccination and a more positive attitude towards their own health and health of their daughters(s) after the community meeting compared with their knowledge and attitude levels before the community meeting. Our proposed sample size of 500 women will achieve 95% power to detect a significant difference in the 95% improvement in knowledge and attitude in adult women against a 90% population improvement rule using a two-sided exact test with a significance level of 0.05.
Data analysis plan. We will measure and compare the pre- and post-meeting women' knowledge score regarding cervical cancer screening and HPV vaccination and women's attitudes towards their own health and health of their daughter(s). Therefore, we will determine the percentage of women who have an improved knowledge and attitudes after the MDP meeting. We will test the estimated knowledge and attitude improvement rates (for adult women screening and for HPV vaccination of children) based on the enrolled study samples against a 90% population improvement rule using one sample proportion tests with normal proximation. In addition, separate paired t-tests will be conducted to compare women's knowledge and attitude scores obtained pre- and post- meeting.
Hypothesis 2: We will be able to identify women who were invited but decline to participate in the MDP and identify barriers of non-participation by interviewing these women.
Women will be invited to attend the community meetings, and their names will be recorded by the counselor. During the meeting, the counselor will describe the MDP project and invite the meeting attenders for to enroll in the study. Therefore, women who attend the MDP community meeting but decline to participate can be identified by the counselor. The counselor will later contact these women for an interview to determine the reasons for declining participation. In addition, women in the village who did not attend the community meeting can also be located. The counselor will meet with the community leaders to locate women in the village who did not attend the meeting. The counselor will then contact the woman for an interview to determine her reasons of not attending the community meeting. The counselor will make a home visit to the non-participants (women who attended community meeting but decline MDP participation, and women who did not attend community meeting) and interview the woman for her barriers of participation in the MDP.
Sample size and data analysis plan. We expect to interview 20 non-participants. We will identify and report women's specific barriers to participation in the MDP by analyzing contents of the interviews. Specific barriers mentioned by the women will then be grouped into several categories. A potential category may be "lack of confidence in safety of the procedures" (self-collection swab or HPV vaccination of children), "other obligations competing for time", or "cultural-related inhibition". We will report the frequency and percentage of each specific barrier mentioned by the women and 95% confidence intervals.
Hypothesis 3. More than half of the non-participating women will agree to participate in the MDP following the in-person interview with the MDP counselor.
The MDP counselor will encourage the non-participating women to participate the MDP during the interview. The counselor will particularly emphasize on educating the woman about the importance of cervical cancer screening and HPV vaccination of her daughter(s). We expect that of the 20 non-participants interviewed by the MDP counselor, 10 or more women will agree to participate the MDP after the in-person interview. The actual number and percentage of women who agree to participate in the MDP after the interview will be documented.
Sample size consideration and analysis plan for Objective 3: Identify factors that influence short- and longer-term immunity to the 9x HPV vaccine in rural Kenyan girls.
Hypothesis: Specific factors including aflatoxin exposure, poor nutritional status, and others can be identified among 9- to 14-year-old girls that are associated with lower rate of seroconversion and lower antibody titers, 6 and 24 months after receiving the second dose of the 9x HPV vaccine.
Sample size consideration: There were 900 girls enrolled in the MISP-2 project who received 2-dose 9v HPV vaccination during the study. Among these fully vaccinated girls,120 girls will have a blood sample obtained 6-month after receiving the vaccine. The blood sample will be analyzed for aflatoxin and for antibody titers to the nine types represented in the HPV vaccine. Short-term immunity to HPV vaccination will therefore be investigated among these 120 girls enrolled in MISP-2. In the current proposed MISP-4 project, we plan to enroll 2000 girls who will receive 2-doses of 9v HPV vaccine.
To examine the potential effects of nutritional parameters on the immune response to HPV vaccination, 120 girls enrolled in MISP-4 will have a blood sample obtained, approximately 12 months after receiving the 2nd vaccine dose. Antibody titers against the 9 HPV types represented in the vaccine, plasma aflatoxin, and indicators of nutrition (folate, iron, hemoglobin) will be measured. BMI will also be determined.
We assume that for each of the 9 vaccine types, 100% seroconversion will occur among girls who do not have detectable plasma aflatoxin or any indication of malnutrition at the follow-up visits, whereas 80% seroconversion will occur among children who have detectable plasma aflatoxin or malnutrition indication. For the purpose of analysis, we define malnourishment as one or more abnormal values of the tested nutrition parameters. We expect a 30% of girls to have detectable plasma aflatoxin and/or indicators of malnutrition.
We will analyze the short-term and longer-term immune response separately. For each analysis (short-term or longer-term), our proposed sample size of 200 children will provide 97% power to detect a 20% difference in seroconversion between children with and without a specific condition (aflatoxin or malnutrition) at a 0.05 significance level based on a two-sided Z-test with continuity correction and pooled variance.
Data analysis plan. We will report the rates of seroconversion to each of the nine HPV types represented in the 9vHPV vaccine at 24 months after receiving the 2nd vaccine dose. We will report rates of plasma aflatoxin detection and malnutrition in the study sample. We will analyze short-term and longer-term immune responses separately. For either short-term or longer-term responses, relative risks of seroconversion to each specific HPV types will be calculated between girls with and without detectable plasma aflatoxin, and girls with and without malnutrition. Rates of seroconversi
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 2500
- Inclusion Criteria: Kenyan women ages 25 through 49 years who are able/willing to sign informed consent and willing to participate in the community meetings. Kenyan girls, ages 9 through 14 whose mothers are able/willing to sign informed consent to be vaccinated and who can return for the second HPV vaccine dose in 6 to 12 months.
Exclusion Criteria: Kenyan women who are pregnant or are not able/willing to sign informed consent. Girls who are not willing or unable to return for the second HPV vaccine dose.
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Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 2500 people (500 mothers and 2000 daughters) 9-valent HPV vaccine the 2000 daughters will be immunized against HPV using the 9-valent HPV vaccine (Gardasil-9)
- Primary Outcome Measures
Name Time Method Positive HPV test (adult women) six months Women will provide a self collected swab that will be analyzed for high risk HPV.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Moi University
🇰🇪Eldoret, Kenya
Moi University🇰🇪Eldoret, KenyaPhillip Tonui, MDContact0722 609132tonui46@yahoo.co.ukDarron R Brown, MDContact317-407-9034darbrow@iu.edu