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

Eunike Velleuer, Ralf Dietrich, Natalia Pomjanski, Isabela Karoline de Santana Almeida Araujo, Bruno Eduardo Silva de Araujo, Isis Sroka, Stefan Biesterfeld, Alfred Böcking, Martin Schramm, Eunike Velleuer, Ralf Dietrich, Natalia Pomjanski, Isabela Karoline de Santana Almeida Araujo, Bruno Eduardo Silva de Araujo, Isis Sroka, Stefan Biesterfeld, Alfred Böcking, Martin Schramm

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.

Keywords: Fanconi anemia; cytology; early detection of cancer; image cytometry; oral cancer; sensitivity; squamous intraepithelial lesions.

© 2020 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

References

    1. Auerbach AD. Fanconi anemia and its diagnosis. Mutat Res. 2009;668:4-10.
    1. Lin J, Kutler DI. Why otolaryngologists need to be aware of Fanconi anemia. Otolaryngol Clin North Am. 2013;46:567-577.
    1. Alter BP, Joenje H, Oostra AB, Pals G. Fanconi anemia: adult head and neck cancer and hematopoietic mosaicism. Arch Otolaryngol Head Neck Surg. 2005;131:635-639.
    1. Kutler DI, Singh B, Satagopan J, et al. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood. 2003;101:1249-1256.
    1. Velleuer E, Dietrich R. Fanconi anemia: young patients at high risk for squamous cell carcinoma. Mol Cell Pediatr. 2014;1:9.
    1. Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica. 2018;103:30-39.
    1. Alter BP, Giri N, Savage SA, Quint WG, de Koning MN, Schiffman M. Squamous cell carcinomas in patients with Fanconi anemia and dyskeratosis congenita: a search for human papillomavirus. Int J Cancer. 2013;133:1513-1515.
    1. Mizumoto A, Ohashi S, Hirohashi K, Amanuma Y, Matsuda T, Muto M. Molecular mechanisms of acetaldehyde-mediated carcinogenesis in squamous epithelium. Int J Mol Sci. 2017;18(9).
    1. Henrich B, Rumming M, Sczyrba A, et al. Mycoplasma salivarium as a dominant coloniser of Fanconi anaemia associated oral carcinoma. PLoS One. 2014;9:e92297.
    1. Furquim CP, Soares GM, Ribeiro LL, et al. The salivary microbiome and oral cancer risk: a pilot study in Fanconi anemia. J Dent Res. 2017;96:292-299.
    1. Kutler DI, Patel KR, Auerbach AD, et al. Natural history and management of Fanconi anemia patients with head and neck cancer: a 10-year follow-up. Laryngoscope. 2016;126:870-879.
    1. Birkeland AC, Auerbach AD, Sanborn E, et al. Postoperative clinical radiosensitivity in patients with Fanconi anemia and head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2011;137:930-934.
    1. Sayan A, Wijesinghe S, Paraneetharan S, Ilankovan V. Revisiting lip shave: a solution for disorders of the vermilion border. Br J Oral Maxillofac Surg. 2018;56:60-63.
    1. Smetsers SE, Velleuer E, Dietrich R, et al. Noninvasive molecular screening for oral precancer in Fanconi anemia patients. Cancer Prev Res (Phila). 2015;8:1102-1111.
    1. Fanconi Anemia Research Fund. Fanconi Anemia: Guidelines for Diagnosis and Management. Vol 4. Fanconi Anemia Research Fund; 2014.
    1. Pentenero M, Marino R, Tempia Valenta G, Navone R, Gandolfo S. Microbiopsy a novel sampling technique to early detect dysplastic/malignant alterations in oral mucosal lesions: practicability by general dentists. J Oral Pathol Med. 2014;43:435-440.
    1. Macey R, Walsh T, Brocklehurst P, et al. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database Syst Rev. 2015(5):CD010276.
    1. Mehrotra R, Gupta DK. Exciting new advances in oral cancer diagnosis: avenues to early detection. Head Neck Oncol. 2011;3:33.
    1. Remmerbach TW, Weidenbach H, Pomjanski N, et al. Cytologic and DNA-cytometric early diagnosis of oral cancer. Anal Cell Pathol. 2001;22:211-221.
    1. Maraki D, Hengge UR, Becker J, Boecking A. Very early cytological and DNA-cytometric diagnosis of in situ carcinoma in an immunosuppressed liver transplant recipient. J Oral Pathol Med. 2006;35:58-60.
    1. Maraki D, Becker J, Boecking A. Cytologic and DNA-cytometric very early diagnosis of oral cancer. J Oral Pathol Med. 2004;33:398-404.
    1. Alaizari NA, Sperandio M, Odell EW, Peruzzo D, Al-Maweri SA. Meta-analysis of the predictive value of DNA aneuploidy in malignant transformation of oral potentially malignant disorders. J Oral Pathol Med. 2018;47:97-103.
    1. van Zyl AW, van Heerden MB, Langenegger E, van Heerden WF. Correlation between dysplasia and ploidy status in oral leukoplakia. Head Neck Pathol. 2012;6:322-327.
    1. Hogmo A, Lindskog S, Lindholm J, Kuylenstierna R, Auer G, Munck-Wikland E. Preneoplastic oral lesions: the clinical value of image cytometry DNA analysis, p53 and p21/WAF1 expression. Anticancer Res. 1998;18:3645-3650.
    1. Donadini A, Maffei M, Cavallero A, et al. Oral cancer genesis and progression: DNA near-diploid aneuploidization and endoreduplication by high resolution flow cytometry. Cell Oncol. 2010;32:373-383.
    1. Ramadas K, Lucas E, Thomas G, et al. A Digital Manual for the Early Diagnosis of Oral Neoplasia. Physical Examination of the Oral Cavity. IARC Press; 2019. Accessed March 13, 2019.
    1. H Alsarraf A, Kujan O, Farah CS. The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Pathol Med. 2018;47:104-116.
    1. Alsarraf A, Kujan O, Farah CS. Liquid-based oral brush cytology in the diagnosis of oral leukoplakia using a modified Bethesda Cytology system. J Oral Pathol Med. 2018;47:887-894.
    1. Remmerbach TW, Meyer-Ebrecht D, Aach T, et al. Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer. Cancer. 2009;117:228-235.
    1. Böcking A. Standardisierte Befunderstellung in der extragenitalen Zytologie. Der Pathologe. 1998;19:235-236.
    1. Bocking A. DNA measurements. When and why? In: Wied GL, Keebler CM, Rosenthal DL, eds. Compendium on Quality Assurance, Proficiency Testing, and Workload Limitations. Tutorials of Cytology; 1995:170-188.
    1. Schramm M, Wrobel C, Born I, et al. Equivocal cytology in lung cancer diagnosis: improvement of diagnostic accuracy using adjuvant multicolor FISH, DNA-image cytometry, and quantitative promoter hypermethylation analysis. Cancer Cytopathol. 2011;119:177-192.
    1. Feulgen R, Rossenbeck H. Mikroskopisch-chemischer Nachweis einer Nucleinsaure vom Typus der Thymonnucleinsaure und die darauf beruhende elektive Färbung von Zellkernen in mikroskopischen Präparaten. Hoppe Seylers Z Physiol Chem. 1924:203-248.
    1. Giroud F, Haroske G, Reith A, Bocking A. 1997 ESACP consensus report on diagnostic DNA image cytometry. Part II: specific recommendations for quality assurance. European Society for Analytical Cellular Pathology. Anal Cell Pathol. 1998;17:201-208.
    1. Haroske G, Baak JP, Danielsen H, et al. Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol. 2001;23:89-95.
    1. Haroske G, Giroud F, Reith A, Bocking A. 1997 ESACP consensus report on diagnostic DNA image cytometry. Part I: basic considerations and recommendations for preparation, measurement and interpretation. European Society for Analytical Cellular Pathology. Anal Cell Pathol. 1998;17:189-200.
    1. Biesterfeld S, Gerres K, Fischer-Wein G, Bocking A. Polyploidy in non-neoplastic tissues. J Clin Pathol. 1994;47:38-42.
    1. Ovrebo JI, Edgar BA. Polyploidy in tissue homeostasis and regeneration. Development. 2018;145(14).
    1. Biesterfeld S, Fuzesi L, Harle F, Bocking A. DNA-cytometric detection of euploid polyploidization in oral lichen ruber planus. Anal Quant Cytol Histol. 1991;13:7-10.
    1. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Vol 9. IARC Press; 2017.
    1. Altman DG, Bland JM. Diagnostic tests 2: predictive values. BMJ. 1994;309:102.
    1. Cohen JF, Korevaar DA, Altman DG, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6:e012799.
    1. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017.
    1. Amit M, Yen TC, Liao CT, et al; International Consortium for Outcome Research (ICOR) in Head and Neck Cancer. Improvement in survival of patients with oral cavity squamous cell carcinoma: an international collaborative study. Cancer. 2013;119:4242-4248.
    1. Nair DR, Pruthy R, Pawar U, Chaturvedi P. Oral cancer: premalignant conditions and screening-an update. J Cancer Res Ther. 2012;8(suppl 1):S57-S66.

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