Diagnostic accuracy of brush biopsy–based cytology for the early detection of oral cancer and precursors in Fanconi anemia

Abstract

BACKGROUND: Individuals with Fanconi anemia (FA) have a 500-fold to 700-fold elevated risk, much earlier onset, and limited therapeutic options for oral squamous cell carcinoma (SCC) compared with the general population. The early detection of SCC, or preferably its precursors, is mandatory to retain curative therapeutic options. Due to frequent synchronic and metachronic oral lesions, tissue biopsies, as usually recommended by guidelines, often are not feasible. In the current study, an alternative strategy for early detection using oral brush biopsy-based cytology was validated regarding its diagnostic accuracy. METHODS: Over a 12-year period, the oral cavities of a large cohort of 713 individuals with FA were inspected systematically and brush biopsy-based cytology of 1233 visible oral lesions was performed. In cases of inconclusive cytology, analysis of DNA ploidy was performed whenever possible. The results were correlated to a long-term clinicopathological follow-up reference standard. RESULTS: A total of 737 lesions were suitable for statistical analysis, including 86 lesions with at least high-grade oral epithelial dysplasia in 30 patients. For cytology, the sensitivity and specificity were 97.7% and 84.5%, respectively. Additional analysis of DNA ploidy increased the sensitivity and specificity to 100% and 92.2%, respectively. CONCLUSIONS: Careful inspection of the oral cavity of individuals with FA followed by brush biopsy-based cytology appears to identify visible oral, potentially malignant and malignant lesions that warrant treatment. Approximately 63% of SCC and precursor lesions are detected at a noninvasive or early stage. Negative cytology or a lack of DNA aneuploidy can exclude high-grade oral epithelial dysplasia or SCC with high accuracy and thus reduce the need for invasive diagnostic biopsies. Cancer Cytopathol 2020;128:403-413.Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Oral Squamous Cell Carcinoma in a Patient with Fanconi Anemia

“…This landmark study included 1233 brush biopsies from an unprecedentedly large cohort of 713 FA patients. They concluded that careful inspection of the oral cavity followed by brush biopsy of suspected lesions detects 63% of SCCs and its precursors at an early stage and negative cytology, especially when combined with DNA ploidy analysis, resulted in a benign course with a high specificity [ 14 ]. The benefits of brush biopsies in FA include low cost and minimal invasiveness in addition to potentially excellent sensitivity and specificity.…”

Oral and Dental Manifestations of Fanconi Anemia

“…Patients with FA have increased predisposition to squamous cell carcinoma of the anogenital tract and head and neck region [11]. In addition, many studies have linked FA to oral cancer [7,12,13] and some have assessed the risk of developing oral cancer [14,15].…”

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

“…The MN frequency was found to be such a good biomarker of chromosomal fragility in epithelial cells that it is already being studied as an endpoint in clinical trials for chemoprevention interventions [120]. The second one studied brush biopsy specimens from oral lesions of patients with FA and showed that DNA aneuploidy is a good biomarker for oral epithelial dysplasia or SCC [121].…”