Abstract LB-248: Minimally-invasive “cytology-on-chip” assay combined with continuous risk index for screening and surveillance of oral cancer in patients with Fanconi anemia

Fanconi Anemia (FA) is an autosomal recessive disorder caused by mutations of DNA repair genes. The risk of oral cancer (OC) among FA patients is 800-times higher than in the general population, occurring at younger ages. Hematopoietic stem cell transplantation (HSCT), which greatly extends the life-expectancy in FA patients further increases the risk of OC in these patients. Patients with FA cannot tolerate chemo-and radiation therapy; hence, early detection of OC is critical to improve survival. Objective: To investigate the role of a numerical index for monitoring OC progression applied to FA patients in combination with a microfluidic “cytology-on-chip” assay and autofluorescence visualization (AFV) using VELscope (Visually Enhanced Lesion scope). Methods: Patients attending the Meeting for Adults with FA, held in Baltimore, Maryland in March 2014 underwent a conventional oral examination followed by AFV. Transepithelial brush samples of mucosal lesions suspected of being oral potentially malignant disorders (OPMD) were obtained using Orcellex® brush (Rovers Medical Devices, Oss, The Netherlands) and transported in ThinPrep® CytoLyt® for cytology-on-chip assays. A numerical OC risk index (0-100) developed and validated on 506 prospectively recruited non-FA patients with OPMD was applied to site-matched brush biopsy samples of FA patients. Results: A total of 28 FA patients (Age range: 18-61 yrs., M = 9, F = 19) participated in this study, of whom 13 have had HSCT. The majority of these lesions (89%) revealed loss of fluorescence (LOF+ve) with AFV. Compared to a cohort of prospectively recruited non-FA patients with OPMD (mean = 36.71, SD = 33.60), the mean OC risk index score for FA patients was 50.66 (SD = 32.83). Additionally, HSCT-recipient FA patients exhibited higher risk index scores (mean = 58.69, SD = 32.16) compared to non -HSCT-recipient FA patients (mean = 40.34, SD = 33.08). The frequency of nuclear aberrations such as micronuclei, bi- and poly-nucleated cells was significantly higher in FA patient cells than healthy controls and significantly higher in LOF+ve compared to LOV-negative OPMD. Two samples exhibited significantly higher WBC (white blood cell) counts, an indicator of inflammation; both were from LOF+ve OPMD found in HSCT-recipient FA patients. Conclusion: FA patients who are HSCT recipients have significantly higher OC risk index scores as well as increased prevalence of LOF+ve OPMD that demonstrate higher incidence of nuclear aberrations and inflammation. These findings are consistent with recent reports that HSCT in FA patients increases their risk for oral cancer. Therefore, use of the OC numerical index and cytology-on-chip assay in combination with AFV may improve the efficacy of conventional oral examination for long-term surveillance of OC in this high-risk patient population, while minimizing unwarranted scalpel biopsies. Citation Format: Timothy J. Abram, Pierre N. Floriano, Rameez Raja, Nancy Bass, Anne Gillenwater, Nadarajah Vigneswaran, John T. McDevitt. Minimally-invasive “cytology-on-chip” assay combined with continuous risk index for screening and surveillance of oral cancer in patients with Fanconi anemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-248.