Oral Dysplasia and Oral Cavity Cancer Risk in Dental and Medical Surveillance Settings Using a Chairside Chip-Based Cytopathology Tool

摘要 在美国，每年约有50,000人被诊断为口腔和咽癌(OPC (10/100,000发病率)。此外，口腔上皮异型增生(OED)大约是OPC的15倍。 已知，被诊断为OED的患者有恶性转化(MT)的风险，而那些接受治疗的患者 口腔鳞状细胞癌(OSCC)是已知的高风险的癌症复发(CR)。的确有 对于这些患者的最佳临床监测路径，几乎没有达成共识。具有以下历史的个人 口腔鳞状细胞癌和潜在恶性口腔病变(PMOL)携带OED/OSCC的临床表现差异很大。 表现与口腔病变无恶性潜在性重叠。因此，临床医生可能不愿执行 对这些病人进行了连续的手术刀活组织检查。市场上可获得的诊断辅助设备缺乏足够的临床应用 跨病变疾病谱的验证。当口腔鳞状细胞癌或高级别OED被早期诊断时， 有机会提供适当的及时治疗，患者的预后可以显著改善。因此，在那里 迫切需要新的高效、无创、精确的口腔病变诊断技术 为个别病人的需要量身定做。 这项多机构前瞻性队列研究试图利用和优化第一点口腔护理 细胞病理学工具(POCOCT)--一种微流控组合和基于单细胞图像的数据采集系统 使用人工智能，并解释包括核F-肌动蛋白在内的&gt；100图像特征，以实现精确度 口腔损伤诊断有待完成。便携式诊断工具和嵌入式算法将针对以下方面进行优化 第一次建立二级和三级医疗机构。在这项R01研究中，POCOCT派生的OSCC CR和OED 将开发MT模型，以阐明人口和患者特定数字指标的动态变化 产生与CR和MT风险相关的关键信息。虽然过去的努力集中在一个时间点上，但这一次 在监测期间，将使用相同的基于多模式芯片的方法重复采样，以确定价值 转换为MT和CR的速度。本R01研究的主要目标是：(1)确定 细胞学特征，当随着时间的推移连续检查时，可以导致更好的CR风险预测，(2)到 确定相同的征象是否可以比传统的临床诊断更早发现局部复发 途径，以及(3)进一步优化POCOCT用于MT和CR的精确病变诊断 已确定的生物标志物，包括核F-肌动蛋白，以及通过深度学习确定的稀有细胞表型。 R01将利用独特的NIDCR-Grand Opportunity数据库实现新的精确度范例 诊断。高危患者将在二级和三级护理环境中每隔一段时间进行纵向监测， 随着时间的推移，将使用个性化的多变量细胞学签名来确定它们的风险轨迹 以及初始值。这项前瞻性纵向队列研究具有更准确的病变诊断的潜力， 提高患者存活率和整体生活质量。

ABSTRACT In the US, approximately 50,000 oral and pharyngeal cancers (OPCs) are diagnosed annually (10/100,000 incidence). Further, oral epithelial dysplasia (OED) is about 15 times more common than OPC. Patients diagnosed with OED are known to be at risk for malignant transformation (MT), and those treated for oral squamous cell carcinoma (OSCC) are known to be at elevated risk for cancer recurrence (CR). There is little consensus about the optimal clinical surveillance pathways for these patients. Individuals with a history of OSCC and potentially malignant oral lesions (PMOLs) harboring OED/OSCC can have widely variable clinical presentation that overlaps with oral lesions of no malignant potential. Thus, clinicians may be reluctant to perform serial scalpel biopsies on these patients. Commercially available diagnostic adjuncts lack adequate clinical validation across the lesion disease spectrum. When OSCC or high-grade OED is diagnosed early, there is an opportunity to provide appropriate timely treatment, and patient outcomes can improve dramatically. Thus, there is a compelling need for new highly effective non-invasive precision oral lesion diagnostic technologies that can be tailored for the needs of individual patients. This multi-institution prospective cohort study seeks to utilize and optimize first Point-of-Care Oral Cytopathology Tool (POCOCT), a microfluidics ensemble and single cell image-based data acquisition system employing artificial intelligence with interpretation of >100 image features including nuclear F-actin for precision oral lesion diagnostics to be completed. Portable diagnostic tools and embedded algorithms will be optimized for secondary and tertiary care settings for the first time. In this R01 study, POCOCT-derived OSCC CR and OED MT models will be developed to elucidate population and patient-specific dynamic changes in numerical index that yield key information related to CR and risk of MT. While past efforts focused on a single time point, this same multimodal chip-based approach will be used to sample repeatedly during surveillance to identify the value of speed of change to MT and CR. The overarching goals of this R01 study are: (1) to determine whether cytological signatures, when examined serially over time, can lead to better risk prediction for CR, (2) to determine if the same signatures can lead to earlier detection of local recurrence than the traditional clinical pathway, and (3) to further optimize the POCOCT for precision lesion diagnostics of MT and CR using newly identified biomarkers, including nuclear F-actin, and rare cell phenotypes identified by deep learning. This R01 will leverage unique NIDCR-Grand Opportunity databases for a new paradigm of precision diagnostics. High risk patients will be longitudinally monitored in secondary and tertiary care settings at intervals, and their risk trajectory will be established over time using personalized multivariate cytological signatures as well as initial values. This prospective longitudinal cohort study has potential for more accurate lesion diagnosis, improving patient survival and overall quality of life.