Biophotonics Noninvasive Detection of Ovarian Cancer

描述（由申请人提供）：卵巢癌是所有主要癌症中最致命的癌症之一。虽然早期疾病通常可以通过手术治愈，但大多数妇女被诊断出来的症状是疾病晚期的前兆。这强调了对无症状妇女进行筛查的紧迫性。然而，目前没有一种技术在临床上被推荐，因为无法准确识别有风险的妇女。因此，必须开发一种高度准确、微创、廉价的检测方法，在临床重要（侵袭性）疾病的早期阶段进行检测。理想情况下，这可以与子宫颈抹片检查相结合。我们提出了一种新的卵巢癌筛查策略，该策略基于通过我们新颖的生物光子学方法在临床实际部位（子宫内膜或子宫颈）识别卵巢野癌，类似于我们在结肠，肺和胰腺中的成功项目。最具侵袭性的浆液性卵巢癌亚型（迄今为止卵巢癌死亡的主要原因）最初在卵巢外的输卵管膜中发展，这一事实强调了该方法的可行性。因此，与输卵管相连的妇科道的其他部位（如子宫内膜和宫颈内膜）已显示出癌变。虽然在显微镜下是正常的，但在这个领域的细胞会发生一些改变，包括遗传的、表观遗传的和纳米结构的。这为卵巢癌的风险分层提供了一个机会，通过在子宫内膜或子宫颈等易于接近的部位检测场效应。对这些病人进行更严格和积极的评估是必要的。这些纳米结构的变化可以通过一种新颖的生物光子学技术，部分波光谱（PWS）显微镜以实用和高度精确的方式检测。我们的试验数据表明，子宫内膜和宫颈细胞纳米结构的改变对场癌变非常敏感，因此可能作为卵巢癌的强有力的生物标志物。在这项研究中，我们将探索使用PWS检测这些纳米级改变的可行性，重点是早期可治愈的卵巢癌。我们将验证在人口统计学、危险因素、非卵巢恶性肿瘤和非肿瘤病变方面没有混淆。该项目将为未来更大规模的临床验证提供必要的数据。这种新模式可能会改变卵巢癌筛查的临床实践。我们设想这项检查可以由妇科医生在年度检查中进行，类似于宫颈肿瘤的涂片检查。

DESCRIPTION (provided by applicant): Ovarian cancer is one of the deadliest of all major cancers. While early stage disease is generally curable with surgery, most women are diagnosed because of symptoms which are a harbinger of advanced disease. This underscores the urgency for screening asymptomatic women. However, none of the current techniques are clinically recommended because of the inability to accurately identify at-risk women. Therefore, it is mandatory to develop a highly accurate, minimally intrusive, inexpensive test that targets clinically important (aggressive) disease at an early stage. Ideally this could be coupled with the Pap smear program. We propose a new ovarian cancer screening strategy based on identifying ovarian field cancerization at a clinically practical site (endometrium or cervix) through our novel biophotonics approach analogous with our successful programs in the colon, lung and pancreas. The feasibility of the approach is underscored by the fact that the most aggressive serous subtype of ovarian cancer (by far the leading cause of ovarian cancer mortality) initially develops outside of the ovary, in the fimbrae of the fallopian tubes. Accordingly, other areas of the gynecological tract that are contiguous with the fallopian tubes (e.g. endometrium and endocervix) have been shown to exhibit field carcinogenesis alterations. Although microscopically normal, cells in this field acquire a number of alterations including genetic, epigenetic and nanoarchitectural. This presents an opportunity to risk- stratify for ovarian cancer through detection of the field effect in a readily accessible site such as endometrium or cervix. More rigorous and aggressive evaluation of these patients would then be warranted. These nanoarchitectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy. Our pilot data show that the alteration of nanoscale architecture in endometrial and cervical cells is exquisitely sensitive to field carcinogenesis and, hence, may serve as a robust biomarker for ovarian cancer. In this study, we will explore the feasibility of using PWS to detect these nanoscale alterations focusing on early stage, curable ovarian cancers. We will validate that there is no confounding with regards to demographics, risk factors and non-ovarian malignancies and non-neoplastic lesions. This project will provide the requisite data for future larger scale clinical validation. This novel paradigm could transform the clinical practice of ovarian cancer screening. We envision that this test can be performed by a gynecologist during an annual exam, similar to the pap-smear for cervical neoplasia. PUBLIC HEALTH RELEVANCE: Ovarian cancer is one of the deadliest of all major cancers with no effective screening currently available. We propose a new, minimally invasive ovarian cancer screening strategy that would be performed by a gynecologist during an annual exam, similar to the pap-smear for cervical neoplasia.