Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells

Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (L_d). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in L_d (% fold-increase > 50%, p-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with micro-RNA expression data. What's new? Ovarian cancer is frequently fatal because it is not detected until it has progressed to late-stage metastatic disease, and new techniques for early detection are sorely needed. Sometimes, apparently normal cells can undergo changes similar to the cancer cells, in a phenomenon called "field carcinogenesis." In these instances, multiple cancers arise in different sites within the same region. In this paper, the authors employ a novel technique, partial wave spectroscopy (PWS) to detect ovarian field carcinogenesis by looking for nanoscale changes in the architecture of endometrial and cervical cells. This report signifies the first demonstration that PWS nanocytology can detect cellular structures at such a small scale. Using this technique to detect ovarian field carcinogenesis could represent a minimally invasive approach to early intervention for ovarian cancer.