TY - JOUR
T1 - Diagnostic accuracy of brush biopsy–based cytology for the early detection of oral cancer and precursors in Fanconi anemia
AU - Velleuer, Eunike
AU - Dietrich, Ralf
AU - Pomjanski, Natalia
AU - de Santana Almeida Araujo, Isabela Karoline
AU - Silva de Araujo, Bruno Eduardo
AU - Sroka, Isis
AU - Biesterfeld, Stefan
AU - Böcking, Alfred
AU - Schramm, Martin
N1 - Funding Information:
Eunike Velleuer, Ralf Dietrich, Natalia Pomjanski, Bruno Eduardo Silva de Araujo, Stefan Biesterfeld, and Martin Schramm report grants from German Fanconi Anemia Support Group. (Eschau, Germany) (since 2006) and grants from the Fanconi Anemia Research Fund (Eugene, Oregon) (since 2013) for work performed as part of the current study. Isabela Karoline de Santana Almeida Araujo has received grants from German Fanconi Anemia Support Group (Eschau, Germany) and Fanconi Anemia Foundation Germany for work performed as part of the current study. Alfred Böcking has received a grant from Motic Company (Xiamen, China) (until 2009) for the development of instruments for DNA image cytometry for work performed as part of the current study. Isis Sroka made no disclosures.
Funding Information:
Eunike Velleuer, Ralf Dietrich, Natalia Pomjanski, Bruno Eduardo Silva de Araujo, Stefan Biesterfeld, and Martin Schramm report grants from German Fanconi Anemia Support Group. (Eschau, Germany) (since 2006) and grants from the Fanconi Anemia Research Fund (Eugene, Oregon) (since 2013) for work performed as part of the current study. Isabela Karoline de Santana Almeida Araujo has received grants from German Fanconi Anemia Support Group (Eschau, Germany) and Fanconi Anemia Foundation Germany for work performed as part of the current study. Alfred Böcking has received a grant from Motic Company (Xiamen, China) (until 2009) for the development of instruments for DNA image cytometry for work performed as part of the current study. Isis Sroka made no disclosures. The study “Reducing the burden of squamous cell carcinoma in fanconi anemia” was funded by the German Fanconi Anemia Support Group (Eschau, Germany) and by the Fanconi Anemia Research Fund (Eugene, Oregon, Funder DOI: 10.13039/100002086).
Publisher Copyright:
© 2020 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Fanconi anemia
KW - cytology
KW - early detection of cancer
KW - image cytometry
KW - oral cancer
KW - sensitivity
KW - squamous intraepithelial lesions
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U2 - 10.1002/cncy.22249
DO - 10.1002/cncy.22249
M3 - Article
C2 - 32022466
AN - SCOPUS:85078989526
SN - 1934-662X
VL - 128
SP - 403
EP - 413
JO - Cancer cytopathology
JF - Cancer cytopathology
IS - 6
ER -