Evaluation of Static DNA Ploidy Analysis Using Conventional Brush Biopsy-Based Cytology Samples as an Adjuvant Diagnostic Tool for the Detection of a Malignant Transformation in Potentially Oral Malignant Diseases: A Prospective Study

SIMPLE SUMMARY: Oral cancer is one of the most common malignant diseases worldwide. What is particularly challenging is not the visual detection of a change in the oral cavity, since this is a clearly visible area, but rather the classification between benign and malignant lesions. With brush biopsies and the evaluation of the DNA content of cells using image cytometry, an examination method was found that is non-invasive and offers a patient-friendly possibility to clarify changes in the oral mucosa. The application of the method is controversial for various reasons. With a cohort of 602 cases, we have examined the effectiveness of this examination method on different oral potentially malignant disorders as well as on a large number of confirmed squamous cell carcinomas. In our study, we confirm the efficiency of DNA ploidy analysis to improve the diagnostic accuracy of conventional cytology. ABSTRACT: Background: The accuracy of DNA image cytometry as an investigation method for potentially malignant disorders of the oral cavity is currently still a subject of controversy, due to inconsistently applied definitions of DNA aneuploidy, small cohorts and different application techniques of the method. The aim of this study was to examine the accuracy of the method as a supplementary diagnostic tool in addition to the cytological examination using internationally consented definitions for DNA aneuploidy. Methods: A total of 602 samples from 467 patients with various oral lesions were included in this prospective study. Brush biopsies from each patient were first cytologically examined and categorized by a pathologist, second evaluated using DNA image cytometry, and finally compared to either histological biopsy result or clinical outcome. Results: Using the standard definition of DNA aneuploidy, we achieved a sensitivity of 93.5%, a positive predictive value for the detection of malignant cells of 98.0%, and an area under the curve of 0.96 of DNA ploidy analysis for the detection of severe oral epithelial dysplasia, carcinoma in situ or oral squamous cell carcinoma. Importantly, using logistic regression and a two-step model, we were able to describe the increased association between DNA-ICM and the detection of malignant cells (OR = 201.6) as a secondary predictor in addition to cytology (OR = 11.90). Conclusion: In summary, this study has shown that DNA ploidy analysis based on conventional specimens of oral brush biopsies is a highly sensitive, non-invasive, patient-friendly method that should be considered as an additional diagnostic tool for detecting malignant changes in the oral cavity.