Einstein/Rwanda/DRC Consortium for Research in HIV/HPV Malignancies

爱因斯坦/卢旺达/刚果民主共和国 HIV/HPV 恶性肿瘤研究联盟

• 批准号: 10084654
• 负责人: Kathryn M. Anastos
• 金额: $ 33.37万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10084654
• 关键词: 12 year old; 15 year old; Address; Adult; Africa; Africa South of the Sahara; Anogenital venereal warts; Antibodies; Antibody titer measurement; Anus; Bedside Testings; Birth; Blood; Cancer Burden; Cancer Etiology; Cervical; Cervical Cancer Screening; Cessation of life; Clinical Research; Colposcopy; Country; Data; Dose; Effectiveness; Enrollment; Enzyme-Linked Immunosorbent Assay; Future; Gardasil; General Population; Generations; Genotype; Goals; HIV; HIV Infections; HIV Seronegativity; HPV-High Risk; Health Planning; High Prevalence; High Risk Woman; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 11; Human papillomavirus 16; Human papillomavirus 18; Human papillomavirus 6; Immune response; Immunity; Immunocompetent; Impairment; Infection; Lateral; Locales; Long-Term Effects; Longitudinal Studies; Malignant Neoplasms; Malignant Vaginal Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of penis; Malignant neoplasm of vulva; Measures; Medical; Medicine; Methods; Military Hospitals; Natural History; Observational Study; Oral; Outcome; Performance; Population; Population Study; Prevalence; Prevention strategy; Prospective Studies; Prospective cohort study; Public Health; Reporting; Research; Resolution; Resources; Risk; Risk Factors; Rwanda; Safety; Sampling; Schools; Secondary to; Sensitivity and Specificity; Specimen; Surrogate Endpoint; Target Populations; Testing; Universities; Vaccinated; Vaccination; Virus-like particle; Visit; Woman; World Health Organization; aged; base; carcinogenicity; cervical cancer prevention; cervicovaginal; cervicovaginal microbiome; chronic infection; cohort; college; comparison group; cost; elementary school; follow-up; girls; immunogenicity; innovation; malignant oropharynx neoplasm; oral infection; point of care; programs; prophylactic; protective effect; rare cancer; response; sixth grade; vaccine effectiveness; validation studies; virtual; young adult; young man; young woman

Abstract: 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 high-risk human papillomavirus (hrHPV). HPV16 causes ~55- 60% and HPV18 causes ~10-15% of cervical cancer while the remaining ~12 HPV types cause the remaining 25-30% of cervical cancer. hrHPV, 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 shown to be nearly 100% protective against incident infection and related abnormalities against the target HPV types 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. In 2011, Rwanda, a high-burden cervical cancer country in East Africa that has an HIV prevalence in adult women of 3.3%, 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 Rwanda 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 did not receive HPV vaccination (birth cohorts before 1997). We will compare the cervical, anal, and oral prevalent and 6-month persistent HPV6/11/16/18 infections in 757 HPV-vaccinated WLWH to those in 757 unvaccinated WLWH. We 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. We also will validate a low-cost, simple point-of-care test for HPV16 antibodies as method to verify/determine HPV vaccination status. Finally, we will investigate the risk factors, including the cervicovaginal microbiome, for HPV persistence in WLWH. Our (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 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 call for the global control of cervical cancer.

摘要： 宫颈癌是全球第四大常见癌症和与癌症相关的死亡原因； 许多资源较低的地区，特别是撒哈拉以南非洲(SSA)，这是最常见的。几乎所有的 宫颈癌和癌前病变是由高危人乳头瘤病毒(HrHPV)引起的。HPV16引起~55- 60%的宫颈癌和HPV18导致约10-15%的宫颈癌，其余约12种HPV型导致其余的宫颈癌 25%-30%的宫颈癌。HrHPV，主要是HPV16，也导致大多数肛门、外阴、阴道和阴茎 癌症和相当大比例的口咽癌。预防性HPV疫苗已经被 已开发并已显示出对意外感染和相关异常几乎100%的保护 与普通人群中的目标HPV类型进行比较。然而，证明其有效性的证据 携带人类免疫缺陷病毒(WLWH)的妇女是否接种预防性HPV疫苗尚不清楚。 由于对HPV的免疫反应受损，艾滋病毒感染会增加患宫颈癌的风险。 2011年，卢旺达，一个东非高负担的宫颈癌国家，艾滋病毒在 3.3%的成年妇女使用Gardasil®实施了全国HPV疫苗接种计划，该计划可保护 对于HPV16和HPV18这两种导致70%的宫颈癌的HPV类型，以及HPV6和HPV11， 引起约90%的肛门生殖器疣的两种类型(HPV6/11/16/18)。他们的计划已经达到了90% 每年覆盖目标人群，主要是12岁的女孩。实施一项高度的 成功的HPV疫苗接种计划和艾滋病毒的高流行率，以及研究和医疗 爱因斯坦医学院(爱因斯坦)在卢旺达军事医院帮助建立的能力 (RMH)和卢旺达大学(UR)的合作，使卢旺达成为研究HPV长期影响的理想场所 WLWH的疫苗接种。 为了回答有关卢旺达WLWH HPV疫苗有效性和免疫力的问题，合作者 在爱因斯坦，RMH和UR将对WLWH和HIV阴性(HIV[-])女性进行一项观察性研究 DID(1997年及以后的出生队列)和WLWH没有接受HPV疫苗接种(1997年之前的出生队列)。我们 将比较757例宫颈、肛门、口腔和6个月持续HPV6/11/16/18感染情况 对757例未接种HPV的WLWH进行HPV免疫接种。我们还将比较人乳头瘤病毒免疫 548名HPV接种者WLWH对548名HPV接种者的应答及转换的影响 2015年，Gardasil从3剂增加到2剂。我们还将验证低成本、简单的医疗点测试 HPV16抗体作为验证/确定HPV疫苗接种情况的方法。最后，我们将调查风险 HPV在WLWH中持续存在的因素，包括宫颈阴道微生物群。我们的(长期)目标是 建立WLWH队列，我们可以在队列中检查HPV疫苗接种的长期效果 WLWH现在和未来。这一贡献意义重大，因为它将确立 在WLWH接种HPV疫苗居住在SSA，是宫颈癌风险最高的妇女，对此有 缺乏证据。拟议的研究具有创新性，因为它利用和扩展了当地的研究和 卢旺达检查关于HPV疫苗的一个严重悬而未决的问题的医疗能力 在世界卫生组织呼吁全球控制宫颈癌的背景下取得成效。