The Effectiveness of High Resolution Microendoscopy (HRME) in High Grade Intraepithelial Lesions (HSIL)Diagnosis for People Living with HIV

摘要肛门鳞状细胞癌(Scca)是老年HIV感染者中最常见的癌症之一。 在美国的个人。艾滋病毒感染者患SCCA的风险是普通人群的40-80倍 最近的队列研究报告说，感染艾滋病毒的男性中SCCA的发病率在 49-144/10万人年，大大高于#年之前的宫颈癌发病率 广泛应用宫颈细胞学进行筛查。令人震惊的增长，肛门癌前期和癌症在艾滋病毒- 受感染的人导致了对预防的更加重视。现行艾滋病毒初级保健指南(纽约 国家艾滋病毒初级保健指南、艾滋病毒医学协会和美国传染病学会) 建议每年进行肛门细胞学筛查，并对高分辨率肛门镜(HRA)引导下的活检进行分流 性行为男性HIV感染者肛门高度上皮内病变的组织学证实 男性(男男性同性恋者)和某些感染艾滋病毒的女性。然而，HRA引导下的HSIL组织学诊断是 资源密集，有几个缺点，包括：广泛的临床医生专业知识/培训；病理成本； 可获得性、口译专业知识；单独就诊进行诊断和治疗；以及患者不适 与不必要的非肿瘤性活检有关，因为基于HRA的可视HSIL的特异性较低 身份证明。我们团队开发了一种便携式、电池供电、高分辨率的显微内窥镜 (MHRME)，提供肛门上皮的亚细胞图像，描绘细胞和形态 与肿瘤形成相关的变化。我们的中心假设是，这种“光学”方法将增加 HRA引导下活组织检查现行标准的效率、临床影响和成本效益。在最近一次 初步试验表明，mHRME对肛门HSIL诊断的敏感性和特异性较高(94%和92% 分别)与肛门活检进行比较。基于我们重要的初步数据，我们现在建议优化 并使用提供实时图像解释的软件界面验证3D成像和HRME 帮助，从而促进经验较少的临床医生在社区或资源不足的环境中使用。 为了验证这一点，我们将进行一项研究，以确定 MHRME‘光学活检’方法与基于HRA的组织活检的当前标准的比较。此外，我们还将 构建、提炼和分析基于HRA的mHRME筛查疾病模型，以确定成本。 HRME在基于HRA的HSIL诊断中的有效性成功的结果将允许 提高人类免疫缺陷病毒感染者肛门癌筛查的有效性和资源利用率 其他上皮性癌症包括子宫颈、口腔、膀胱和胃肠道。

Squamous cell cancer of the anus (SCCA) is one of the most common cancers among aging HIV-infected individuals in the United States. HIV-infected persons are at 40-80-times higher risk for SCCA than the general population, and recent cohort studies report that the incidence of SCCA among HIV-infected men is between 49-144/100,000 person-years, which is substantially higher than the incidence of cervical cancer prior to widespread screening with cervical cytology. The alarming increase in anal precancer and cancer in HIV- infected individuals has led to an increased emphasis on prevention. Current HIV primary care Guidelines (NY state HIV primary care guidelines, HIV Medical Association, and Infectious Diseases Society of America) both recommend annual anal cytology screening, with triage to high resolution anoscopy (HRA)-guided biopsy for histologic confirmation of anal high grade intraepithelial lesions (HSIL) among HIV-infected men who have sex with men (MSM), and certain HIV-infected women. However, HRA-guided histologic diagnosis of HSIL is resource intensive, and has several drawbacks, including: extensive clinician expertise/training; pathology cost, availability, interpretation expertise; separate patient visits for diagnosis and treatment; and patient discomfort associated with unnecessary, non-neoplastic biopsies, given the low specificity of HRA-based visual HSIL identification. Our group has developed a portable, battery-operated, high-resolution microendoscope (mHRME) that provides subcellular images of the anal epithelium, delineating the cellular and morphologic changes associated with neoplasia. Our central hypothesis is that this 'optical' approach will increase the efficiency, clinical impact, and cost-effectiveness of the current standard of HRA-guided biopsy. In a recent pilot trial, the mHRME demonstrated a high sensitivity and specificity of anal HSIL diagnosis (94% and 92% respectively) compared to anal biopsy. Based on our significant preliminary data, we now propose to optimize and validate 3D imaging and HRME with a software interface that provides real- time image interpretation assistance, thus facilitating usage by less-experienced clinicians in community-based or low-resource settings. To validate this, we will conduct a study to determine the efficiency and diagnostic characteristics of an mHRME 'optical biopsy' approach versus the current standard of HRA-based tissue biopsy. In addition, we will construct, refine and analyze a disease model of HRA-based screening with mHRME to determine the cost- effectiveness of incorporating HRME into HRA-based HSIL diagnosis. Successful results will allow for improved efficacy and resource utilization for cancer screening in HIV-infected individuals for anal cancer and other epithelial cancers including the cervix, oral cavity, bladder, and GI tract.