HPV Vaccine Effectiveness Study in Rwandan Women Living With HIV
Long-Term Human Papillomavirus Vaccination Effectiveness and Immunity in Rwandan Women Living With and Without Human Immunodeficiency Virus
Study Overview
Status
Intervention / Treatment
Detailed Description
Cervical cancer is the 4th most common cancer and cause of cancer-related death in women globally; in many lower-resource settings, especially sub-Saharan Africa (SSA), it is the most common. Virtually all cervical cancer and precancer are caused by 12-15 high-risk human papillomavirus (HPV) types. HPV16 causes approximately 55-60% and HPV18 causes approximately 10-15% of cervical cancer while the remaining 12 HPV types cause the remaining 25-30% of cervical cancer. High-risk HPV, predominately HPV16, also causes most anal, vulvar, vaginal, and penile cancers and a significant proportion of oropharyngeal cancers. Prophylactic HPV vaccines have been developed and have been shown to be nearly 100% protective against incident HPV infection and related abnormalities in the general population. However, the evidence for the effectiveness of prophylactic HPV vaccines in women living with human immunodeficiency virus (HIV) (WLWH) is less clear. HIV infection increases the risk of cervical cancer due to an impaired immune response to HPV.
Rwanda is a high-burden cervical cancer country where the prevalence of HIV is 3.7% among adult women, with higher HIV prevalence among young women (1). In 2011, Rwanda implemented a national HPV vaccination program with Gardasil®, which protects against HPV16 and HPV18, the two HPV types that cause ~70% of cervical cancer, and HPV6 and HPV11, the two types that cause ~90% of anogenital warts (HPV6/11/16/18). Their program has achieved >90% coverage of the target population, primarily girls aged 12 years, annually. The implementation of a highly successful HPV vaccination program and the high prevalence of HIV, in addition to the research and medical capacity that Albert Einstein College of Medicine (Einstein) has helped to build at the Rwanda Military Hospital (RMH) and University of Rwanda (UR), makes Rwanda the ideal locale to study the long-term effects of HPV vaccination in WLWH.
To answer questions about HPV vaccine effectiveness and immunity in Rwandan WLWH, collaborators at Einstein, RMH, and UR will conduct an observational study of WLWH and HIV-negative (HIV[-]) women who did (birth cohorts 1997 and later) and WLWH who did not (birth cohorts before 1997) receive HPV vaccination through the national vaccination program. The investigators will compare cervicovaginal, anal, and oral prevalent and 6-month persistent HPV6/11/16/18 infections in 757 HPV-vaccinated WLWH to those in 757 unvaccinated WLWH and 757 HPV-vaccinated HIV[-] women. The investigators will also compare the HPV immune response in 548 HPV-vaccinated WLWH to 548 HPV-vaccinated HIV[-] women and the impact of switching from 3 doses to 2 doses of Gardasil® in 2015. Finally, the investigators will investigate the risk factors, including the cervicovaginal microbiome, for prevalent and 6-month persistent HPV infection in young WLWH and HIV[-] women. The long-term goal is to establish a cohort of WLWH in whom we can examine the long-term effectiveness of HPV vaccination in WLWH now and in the future. This contribution is significant as it will establish the population effectiveness of HPV vaccination in WLWH living in SSA, the group of women at the highest risk of cervical cancer, for which there is a dearth of evidence. The proposed research is innovative as it leverages and expands the local research and medical capacity in Rwanda to examine one of the critically unanswered questions about HPV vaccine effectiveness in the context of the World Health Organization's (WHO) call for the elimination of cervical cancer.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Kigali, Rwanda
- Rwanda Military Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Female
- 18-28 years. The age of inclusion criteria will likely be restricted as age-specific enrollment goals are met.
- Physically and mentally able and willing to participate in the study.
- Willing to provide written and signed or thumb printed, informed consent.
- Known to be living with HIV (i.e., enrolled in a treatment program), or consent to HIV testing to confirm HIV status.
Exclusion Criteria:
- Have positive pregnancy test or report to be pregnant at the time of visit or less than 6 weeks post-partum (will be asked to make an appointment 6 or more weeks post-partum)
- Report to be menstruating at the time of visit (will be asked to make new appointment)
- History of hysterectomy and no longer have a cervix
- History of treatment for cervical abnormalities after cervical screening
- History of cervical cancer
- Report no previous sexual activity
- HIV status is unknown, and date of birth is 12/31/1995 or earlier
- Because this study has age-specific enrollment goals for WLWH and HIV[-] women, once those enrollment goals are met for each study group, the respective cohorts will be closed and other eligible women will be excluded.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Group 1
HPV-vaccinated women living with HIV
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Blood collection at enrollment visit
Oral, cervicovaginal and anal specimen collection at enrollment and follow-up visits
Used for management in follow-up visits of persistent anal HPV16/18+ in WLWH
Used for management in follow-up visits of persistent type-specific high-risk HPV cervicovaginal HPV
Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy
Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy that ablation ineligible
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Group 2
HPV-unvaccinated women living with HIV
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Blood collection at enrollment visit
Oral, cervicovaginal and anal specimen collection at enrollment and follow-up visits
Used for management in follow-up visits of persistent anal HPV16/18+ in WLWH
Used for management in follow-up visits of persistent type-specific high-risk HPV cervicovaginal HPV
Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy
Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy that ablation ineligible
|
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Group 3
HIV[-] women who are HPV-vaccinated
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Blood collection at enrollment visit
Oral, cervicovaginal and anal specimen collection at enrollment and follow-up visits
Used for management in follow-up visits of persistent type-specific high-risk HPV cervicovaginal HPV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Change in vaccine effectiveness of prophylactic HPV vaccine
Time Frame: Baseline and up to 12 months
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To measure population effectiveness of prophylactic HPV vaccine in reducing cervicovaginal, anal, and/or oral prevalent and 6-12 month persistent infections by HPV6/11/16/18
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Baseline and up to 12 months
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Change in long-term antibody responses to HPV vaccination
Time Frame: Baseline and up to 12 months
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To quantify, and examine the determinants of, long-term antibody (into young adulthood) responses to HPV vaccination
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Baseline and up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Change in HPV natural history study at 6 months
Time Frame: Baseline and 6 months
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Conduct a natural history study to investigate determinants, including cervicovaginal microbiome (CVM), of short-term HPV persistence in young WLWH and HIV[-] women living in a SSA setting
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Baseline and 6 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in HPV natural history study at 6 months
Time Frame: Baseline and 6 months
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Conduct a natural history study to investigate determinants, including cervicovaginal microbiome (CVM), of short-term HPV persistence in young WLWH and HIV[-] women living in a SSA setting
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Baseline and 6 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marcel Yotebieng, MD, PhD, Albert Einstein College of Medicine
Publications and helpful links
General Publications
- Kundrod KA, Jeronimo J, Vetter B, Maza M, Murenzi G, Phoolcharoen N, Castle PE. Toward 70% cervical cancer screening coverage: Technical challenges and opportunities to increase access to human papillomavirus (HPV) testing. PLOS Glob Public Health. 2023 Aug 16;3(8):e0001982. doi: 10.1371/journal.pgph.0001982. eCollection 2023.
- Murenzi G, Mungo C. Impact of the human papillomavirus vaccine in low-resource settings. Lancet Glob Health. 2023 Jul;11(7):e997-e998. doi: 10.1016/S2214-109X(23)00203-6. Epub 2023 May 16. No abstract available.
- Murangwa A, Desai KT, Gage JC, Murenzi G, Tuyisenge P, Kanyabwisha F, Musafili A, Kubwimana G, Mutesa L, Anastos K, Kim HY, Castle PE. Agreement between Xpert and AmpFire tests for high-risk human papillomavirus among HIV-positive women in Rwanda. Afr J Lab Med. 2022 Oct 19;11(1):1827. doi: 10.4102/ajlm.v11i1.1827. eCollection 2022.
- Murenzi G, Shumbusho F, Hansen N, Munyaneza A, Gage JC, Muhoza B, Kanyabwisha F, Pierz A, Tuyisenge P, Anastos K, Castle PE. Long-term human papillomavirus vaccination effectiveness and immunity in Rwandan women living with and without HIV: a study protocol. BMJ Open. 2022 Aug 25;12(8):e061650. doi: 10.1136/bmjopen-2022-061650.
- Mukherjee A, Ye Y, Wiener HW, Kuniholm MH, Minkoff H, Michel K, Palefsky J, D'Souza G, Rahangdale L, Butler KR, Kempf MC, Sudenga SL, Aouizerat BE, Ojesina AI, Shrestha S. Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer. Cancer Epidemiol Biomarkers Prev. 2023 Sep 1;32(9):1190-1197. doi: 10.1158/1055-9965.EPI-23-0300.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Blood-Borne Infections
- Urogenital Diseases
- Genital Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Immune System Diseases
- Infections
- RNA Virus Infections
- Virus Diseases
- Uterine Diseases
- Genital Diseases, Female
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Genital Neoplasms, Female
- Slow Virus Diseases
- Uterine Cervical Diseases
- Uterine Neoplasms
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Uterine Cervical Neoplasms
- Investigative Techniques
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Minimally Invasive Surgical Procedures
- Diagnostic Techniques, Surgical
- Endoscopy, Gastrointestinal
- Endoscopy, Digestive System
- Diagnostic Techniques, Digestive System
- Endoscopy
- Digestive System Surgical Procedures
- Urogenital Surgical Procedures
- Gynecologic Surgical Procedures
- Obstetric Surgical Procedures
- Diagnostic Techniques, Obstetrical and Gynecological
- Proctoscopy
- Blood Specimen Collection
- Colposcopy
Other Study ID Numbers
- 2021-13087
- 1U54CA254568-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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