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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的：宫颈癌是全球第四大常见癌症，也是全球女性癌症相关死亡的原因；在许多资源匮乏的地区，尤其是撒哈拉以南非洲 (SSA)，这种情况几乎是最常见的。宫颈癌和癌前病变是由高危人乳头瘤病毒 (hrHPV) 引起的~55-。 60% 和 HPV18 导致约 10-15% 的宫颈癌，而其余约 12 种 HPV 类型导致其余的宫颈癌 25-30% 的宫颈癌（主要是 HPV16）也会导致大多数肛门癌、外阴癌、阴道癌和阴茎癌。癌症和很大一部分口咽癌已经接种了预防性 HPV 疫苗。发生事件并已显示出近 100% 的预防感染和相关异常的能力然而，有证据表明，针对一般人群中的目标 HPV 类型是有效的。对于感染人类免疫缺陷病毒 (HIV) (WLWH) 的女性来说，预防性 HPV 疫苗的使用尚不明确。由于对 HPV 的免疫反应受损，HIV 感染会增加患宫颈癌的风险。 2011年，东非子宫颈癌高负担国家卢旺达的艾滋病毒流行情况 3.3% 的成年女性使用 Gardasil® 实施了全国 HPV 疫苗接种计划，该计划可保护针对 HPV16 和 HPV18（这两种 HPV 类型导致约 70% 的宫颈癌），以及 HPV6 和 HPV11，导致约 90% 肛门生殖器疣的两种类型 (HPV6/11/16/18) 他们的计划已实现 >90%。覆盖目标人群，主要是12岁女孩，每年实施高度。成功的 HPV 疫苗接种计划和艾滋病毒的高患病率，以及研究和医疗阿尔伯特·爱因斯坦医学院（爱因斯坦）帮助卢旺达军事医院建立了能力 (RMH) 和卢旺达大学 (UR) 合作，使卢旺达成为研究 HPV 长期影响的理想场所 WLWH 中的疫苗接种。回答有关卢旺达 WLWH 中 HPV 疫苗有效性和免疫力的问题，合作者爱因斯坦、RMH 和 UR 将对 WLWH 和 HIV 阴性 (HIV[-]) 女性进行一项观察性研究接种了疫苗（1997 年及以后的出生队列），WLWH 未接种 HPV 疫苗（1997 年之前的出生队列）。将比较 757 名患者的宫颈、肛门和口腔流行情况以及 6 个月持续性 HPV6/11/16/18 感染情况接种 HPV 疫苗的 WLWH 与 757 名未接种疫苗的 WLWH 的情况我们还将比较 HPV 免疫情况。 548 名接种 HPV 疫苗的 WLWH 对 548 名接种 HPV 疫苗的 HIV[-] 妇女的反应以及转换的影响 2015 年，Gardasil 的剂量从 3 剂增加到 2 剂。我们还将验证一种低成本、简单的现场检测 HPV16 抗体作为验证/确定 HPV 疫苗接种状况的方法最后，我们将调查风险。影响 WLWH 中 HPV 持续存在的因素，包括宫颈阴道微生物组。建立一个 WLWH 队列，我们可以在其中检查 HPV 疫苗接种的长期有效性 WLWH 现在和将来这一贡献都很重要，因为它将确定人口有效性。居住在 SSA 的 WLWH 接种 HPV 疫苗，这些妇女患宫颈癌的风险最高，对此有缺乏证据。拟议的研究具有创新性，因为它利用并扩展了当地的研究和卢旺达的医疗能力有能力检查有关 HPV 疫苗的尚未解答的关键问题之一世界卫生组织呼吁全球控制宫颈癌的有效性。