COMParative ASSessment of p16/Ki-67 DUal Staining Technology in women living with HIV (COMPASS-DUST study)

项目概要 该应用程序为早期职业调查员提供了五年职业发展和研究计划 来自尼日利亚。候选人 Kehinde Okunade 是 2018 年 Fogarty 研究员，通过 HBNU FIC D43 培训 计划及大学医学院妇产科高级讲师 尼日利亚拉各斯。他的应用程序的目标是利用程序提供的受保护时间来 (1) 通过与导师的定期互动，建立和加强导师关系和技能传授 和共同导师； (2) 获得临床流行病学研究的经验技能，并能够将其转化为 公共卫生实践 (3) 进行申请中提出的严格研究； (4) 掌握相关技能 设计和进行端到端临床试验； （五）建立有效的科研合作网络 协调多学科研究项目，以及 (6) 能够撰写、获得和管理资助以开展 研究并撰写手稿以在高影响力期刊上发表。 FIC K43 申请中拟议的研究“p16/Ki-67 DUal 染色的比较评估” 针对感染艾滋病毒的女性的技术 (COMPASS-DUST)”是撒哈拉以南非洲 (sSA) 的首项技术，旨在 评估 p16/Ki-67 双染色技术 (DUST) 在宫颈癌筛查中的表现 感染艾滋病毒的妇女 (WLHIV)。在目标 1 和 2 中，使用参与者内部比较研究设计，我们将 在拉各斯的两个经认可的成人艾滋病毒治疗中心招募 n=300 名 25-65 岁的性活跃 WLHIV 患者， 尼日利亚将 DUST 的性能与目前使用的筛查方法（巴氏涂片、hr-HPV DNA 或 VIA 检测）用于检测高级别宫颈上皮内瘤变 (CIN2/3)。在目标 3 中，我们将使用 前瞻性队列研究设计招募被诊断为低度 CIN (CIN1) 的 WLHIV (n=60) 为期 2 年的 6 个月随访，以检测持续性 CIN1 以及 CIN1 进展为 CIN2/3。调查结果 由于两个原因，这项研究将具有重大的公共卫生意义。首先，他们可以提供证据 存在一种性能更好的筛选方法，用于 WLHIV 中 CIN2/3 的初步和分类检测。 其次，我们可以证明这种高性能测试可以提高长期预测的准确性 通过延长评估之间的间隔来进行筛选，从而降低总体成本并增加 WLHIV 的筛查摄取。 该申请将建立在候选人的背景经验及其导师团队的专业知识的基础上 以及尼日利亚和美国的共同导师，以实现该计划的培训和研究目标。在长期—— 学期中，拟议的研究和培训活动将为候选人提供一套独特的经验 使他能够过渡为独立的医师科学家的技能。

Project Summary This application presents a five-year career development and research program for an early career investigator from Nigeria. The candidate, Kehinde Okunade, is a 2018 Fogarty fellow through the HBNU FIC D43 Training Program and also a Senior Lecturer in Obstetrics and Gynecology at the College of Medicine of the University of Lagos in Nigeria. The goals of his application are to use the protected time provided through the program to (1) Build and strengthen mentoring relationships and skills transfer through regular interactions with mentors and co-mentors; (2) Acquire experiential skills in clinical epidemiologic research and be able to translate this to public health practice (3) Conduct the rigorous research proposed in the application; (4) Acquire skills in the design and conduct of end-to-end clinical trials; (5) Establish research collaboration network and effectively coordinate multidisciplinary research projects, and (6) Be able to write, secure, and manage grants to conduct studies as well as write manuscripts for publication in high-impact journals. The proposed research in the FIC K43 application, “COMParative ASSessment of p16/Ki-67 DUal Staining Technology in women living with HIV (COMPASS-DUST)” is the first in sub-Saharan Africa (sSA) that aims to evaluate the performance of p16/Ki-67 dual staining technology (DUST) in cervical cancer screening among women living with HIV (WLHIV). In Aim 1 and 2, using an intra-participant comparative study design, we will enrol n=300 sexually active WLHIV aged 25–65 years at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting high-grade cervical intraepithelial neoplasia (CIN2/3). In Aim 3, we will use a prospective cohort study design to enrol WLHIV (n=60) who are diagnosed as having low-grade CIN (CIN1) for a 6-monthly follow-up for 2 years to detect persistent CIN1 and progression of CIN1 to CIN2/3. The findings of this study will be of great public health significance for 2 reasons. First, they may provide evidence of the existence of a better performance screening method for the primary and triage detection of CIN2/3 in WLHIV. Secondly, we may demonstrate that this high-performance test can improve the long-term predictive accuracy of screening by extending the intervals between evaluations and thus decrease the overall cost and increase screening uptake in WLHIV. This application will build on the candidate’s background experience and the expertise of his team of mentors and co-mentors in Nigeria and the US to achieve the training and research goals of this program. In the long- term, the proposed research and training activities will provide the candidate with a unique set of experiential skills that will enable him to transition to independence as a physician-scientist.