High resolution imaging & HPV oncoprotein detection for global prevention of cervical cancer

高分辨率成像

基本信息

批准号：
9324154
负责人：
Rebecca R. Richards-Kortum
金额：
$ 57.46万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9324154
关键词：
Acetic Acids Address Adenocarcinoma Alpha Cell Bedside Testings Biological Assay Biological Markers Biopsy Botswana Cancer Etiology Cells Cellular Phone Cervical Cervix Uteri Cessation of life China Cold Therapy Colposcopy Cytology Cytology Histology DNA Detection Developing Countries Development Diagnosis Diagnostic Disease Distal Early Diagnosis Early treatment El Salvador Epithelial Excision HPV-High Risk Healthcare Human Papillomavirus Human Resources Human immunodeficiency virus test Image Image Analysis In Situ In Situ Lesion Investigation Lateral Lesion Loop electrosurgical excision procedure Malignant Neoplasms Malignant neoplasm of cervix uteri Methods Molecular Morbidity - disease rate Nuclear Oncoproteins Outpatients Pap smear Patients Performance Phenotype Pilot Projects Premalignant Process Protocols documentation Research Infrastructure Resolution Resources Risk Rural Side Socioeconomic Status Specificity Specimen Swab Techniques Technology Test Result Testing Time Tissues Training Unnecessary Procedures Visit Visual Woman Work base cancer diagnosis cancer survival case control cervical cancer prevention cost cost effectiveness follow-up global health high resolution imaging high risk imaging biomarker imaging modality improved in situ imaging in vivo low and middle-income countries low socioeconomic status microendoscope microendoscopy mobile computing molecular marker mortality novel novel strategies overexpression performance tests phenotypic biomarker point of care point-of-care diagnostics prevent public health relevance research clinical testing rural setting screening tool urban setting usability wasting

项目摘要

DESCRIPTION (provided by applicant): Cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle- income countries. In the U.S., low socioeconomic status (SES) is strongly correlated with poor cervical cancer survival. In resource-limited settings in the U.S. and abroad, there is a significant need for new point-of-care diagnostics that enable combined detection and treatment of cervical precancer in a single visit. To date, global attempts to implement "see & treat" protocols have been limited by the extremely low specificity of the three existing diagnostic approaches that can be used at the point-of-care. "See & treat" protocols based on imaging (colposcopy or visual inspection with acetic acid (VIA)) or biomarker detection (HPV DNA testing) result in high rates of overtreatment, subjecting patients to unnecessary procedures and wasting healthcare resources. We hypothesize that a combination of imaging and biomarker detection can reduce the high false positive rate of current cervical screening tools. Increased nuclear-to-cytoplasmic (N/C) ratio is one of the best known phenotypic biomarkers of cervical precancer, but can currently only be assessed from cytology or biopsy. We have developed an investigational imaging method, high-resolution microendoscopy (HRME), to identify cervical lesions in situ with increased N/C ratio. In Aim 1, we will adapt the HRME to a mobile platform which incorporates a cell phone to capture, display, analyze, and transmit images. We will then evaluate the performance of the mobile HRME (mHRME) with an existing biomarker (HPV DNA testing) and an investigational biomarker (HPV E7 oncoprotein). In Aim 2, we will evaluate performance of the mHRME in two globally relevant contexts: (A) in a clinical evaluation of 429 women in the U.S., we will assess whether addition of mHRME imaging improves specificity of colposcopy, without significantly reducing sensitivity; (B) in a clinical evaluation of 4,592 women in El Salvador, we will assess whether mHRME imaging improves the specificity of screening by VIA alone, HPV DNA testing alone, or with HPV DNA testing followed by VIA. Overexpression of HPV E7 oncoprotein is one of the best known molecular biomarkers of cervical precancer. To further improve specificity of molecular testing, in Aim 3 we will develop a rapid, low-cost, laterl flow test to detect E7. We will assess test performance using cervical specimens in a nested case-control of 270 patients with and without cervical precancer who participated in Aim 2. This work will provide clinicians in the U.S. and globally with robust, affordable, integrated, point-of care tools to directly image phenotypic changes and detect molecular markers associated with the development and progression of cervical precancer, addressing the poor specificity of current methods. Together, these tools will improve the efficacy and cost-effectiveness of early detection of cervical precancer, allowing diagnosis and treatment in a single visit to prevent the development of invasive cervical cancer.

描述（由申请人提供）：宫颈癌仍然是低收入和中等收入国家妇女癌症死亡的第一或第二主要原因。在美国，低社会经济地位（SES）与宫颈癌的贫困生存密切相关。在美国和国外的资源有限的设置中，需要新的护理点可以在一次访问中综合检测和治疗宫颈预科剂的诊断。迄今为止，全球实施“参见和治疗”协议的尝试受到了可以在护理点上使用的三种现有诊断方法的极低特异性的限制。基于成像（阴道镜检查或用乙酸（通过）视觉检查（通过）或生物标志物检测（HPV DNA测试）的“参见和治疗”方案导致过度治疗率高，使患者接受不必要的程序并浪费医疗保健资源。我们假设成像和生物标志物检测的结合可以降低当前宫颈筛查工具的高假阳性速率。增加的核胞质（N/C）比是宫颈预科剂的最著名的表型生物标志物之一，但目前只能通过细胞学或活检来评估。我们已经开发了一种研究成像方法，高分辨率微观镜检查（HRME），以鉴定N/C比增加的原位宫颈病变。在AIM 1中，我们将将HRME调整到一个移动平台上，该平台结合了手机以捕获，显示，分析和传输图像。然后，我们将使用现有的生物标志物（HPV DNA测试）和研究性生物标志物（HPV E7 Oncoprotein）评估移动HRME（MHRME）的性能。在AIM 2中，我们将评估MHRME在两个全球相关的环境中的性能：（a）在美国429名妇女的临床评估中，我们将评估MHRME成像的添加是否可以提高阴道镜的特异性，而不会显着降低敏感性；（b）在对萨尔瓦多4,592名女性的临床评估中，我们将评估MHRME成像是单独使用VIA，单独使用HPV DNA测试还是进行HPV DNA测试，然后通过VIA进行了HPV DNA测试。 HPV E7癌蛋白的过表达是宫颈预科剂的最著名分子生物标志物之一。为了进一步提高分子测试的特异性，在AIM 3中，我们将开发快速，低成本的后流测试以检测E7。我们将在嵌套的病例对照中使用宫颈标本评估270名患者有或没有宫颈预制剂的患者的宫颈标本，他们参加了AIM 2。这项工作将为美国和全球范围内的临床医生提供强大的，负担得起的，负担得起的，综合的，点护理工具直接成像表型变化并检测与宫颈预科剂的发展和进展相关的分子标记，以解决当前方法的差异特异性。这些工具一起将提高宫颈预科剂早期检测的功效和成本效益，从而在一次访问中进行诊断和治疗，以防止侵入性宫颈癌的发展。