Cytologic and DNA-Cytometric Early Diagnosis of Oral Cancer

Objective. The aim of this prospective study was to report on the diagnostic accuracy of conventional oral exfoliative cytology taken from white‐spotted, ulcerated or other suspicious oral lesions in our clinic. In addition we checked DNA‐image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA‐aneuploidy is a sensitive and specific marker for the early identification of tumor cells in oral brushings. Study design. 251 cytological diagnoses obtained from exfoliative smears of 181 patients from macroscopically suspicious lesions of the oral mucosa and from clinically seemingly benign oral lesions which were exisiced for establishing histological diagnoses were compared with histological and/or clinical follow‐ups of the respective patients. Additionally nuclear DNA‐contents were measured after Feulgen restaining using a TV image analysis system. Results. Sensitivity of our cytological diagnosis on oral smears for the detection of cancer cells was 94.6%, specificity 99.5%, positive predictive value 98.1% and negative predictive value 98.5%. DNA‐aneuploidy was assumed if abnormal DNA‐stemlines or cells with DNA‐content greater 9c were observed. On this basis the prevalence of DNA‐aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 96.4%. Sensitivity of DNA‐aneuploidy in oral smears for the detection of cancer cells was 96.4%, specificity 100%, positive predictive value 100% and negative 99.0%. The combination of both techniques increased the sensivity to 98.2%, specificity to 100%, positive predictive value to 100% and negative to 99.5%. Conclusions. Brush cytology of all visible oral lesions, if they are clinically considered as suspicious for cancer, are an easily practicable, cheap, non‐invasive, painless, safe and accurate screening method for detection of oral precancerous lesions, carcinoma in situ or invasive squamous cell carcinoma in all stages. We conclude that DNA‐image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.

[1]  S. Silverman,et al.  The use of exfoliative cytology for the early diagnosis of oral cancers: is there a role for it in education and private practice? , 2009, Journal of cancer education : the official journal of the American Association for Cancer Education.

[2]  J. Sudbø,et al.  DNA content as a prognostic marker in patients with oral leukoplakia. , 2001, The New England journal of medicine.

[3]  H. Gabbert,et al.  DNA aneuploidy as a specific marker of neoplastic cells in FNAB of the thyroid. , 1999, Analytical and quantitative cytology and histology.

[4]  A. Böcking,et al.  Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva. , 1999, Analytical and quantitative cytology and histology.

[5]  J. Sciubba Improving detection of precancerous and cancerous oral lesions. Computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group. , 1999, Journal of the American Dental Association.

[6]  K. Müller,et al.  Static DNA cytometry as a diagnostic aid in effusion cytology: I. DNA aneuploidy for identification and differentiation of primary and secondary tumors of the serous membranes. , 1998, Analytical and quantitative cytology and histology.

[7]  D. Häussinger,et al.  Static DNA cytometry as a diagnostic aid in effusion cytology: II. DNA aneuploidy for identification of neoplastic cells in equivocal effusions. , 1998, Analytical and quantitative cytology and histology.

[8]  A. Böcking Standardisierte Befund- erstellung in der extragenitalen Zytologie , 1998, Der Pathologe.

[9]  G. Haroske,et al.  Prognostic relevance of DNA image cytometry in oral cavity carcinomas. , 1998, Analytical and quantitative cytology and histology.

[10]  M R Brickley,et al.  Performance of a computer simulated neural network trained to categorise normal, premalignant and malignant oral smears. , 1996, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[11]  E. Eisenberg,et al.  Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia. , 1995, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[12]  F Giroud,et al.  Consensus report of the European Society for Analytical Cellular Pathology task force on standardization of diagnostic DNA image cytometry. , 1995, Analytical and quantitative cytology and histology.

[13]  E. Lane,et al.  DNA and keratin analysis of oral exfoliative cytology in the detection of oral cancer. , 1994, European journal of cancer. Part B, Oral oncology.

[14]  D Kindermann,et al.  Glare-correction in DNA image cytometry. , 1994, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[15]  G. Ogden,et al.  Cytobrush and wooden spatula for oral exfoliative cytology. A comparison. , 1992, Acta cytologica.

[16]  U. Joos,et al.  Cytological detection of epithelial dysplasia in the oral mucosa using feulgen‐DNA‐image cytometry , 1991, Diagnostic cytopathology.

[17]  L. Füzesi,et al.  DNA-cytometric detection of euploid polyploidization in oral lichen ruber planus. , 1991, Analytical and quantitative cytology and histology.

[18]  K. Chew,et al.  Which oral white lesions will become malignant? An image cytometric study. , 1990, Oral surgery, oral medicine, and oral pathology.

[19]  A. Schindler,et al.  Diagnosis of prospective malignancy in koilocytic dysplasias of the cervix with DNA cytometry. , 1989, The Journal of reproductive medicine.

[20]  W. Auffermann,et al.  Automated Feulgen staining with a temperature-controlled staining machine. , 1989, Analytical and quantitative cytology and histology.

[21]  L. Koss The Papanicolaou test for cervical cancer detection. A triumph and a tragedy. , 1989, JAMA.

[22]  C. Mittermayer,et al.  DNA grading of oral squamous carcinomas. A preliminary report. , 1989, International journal of oral and maxillofacial surgery.

[23]  G. Hemstreet,et al.  Cancer detection by quantitative fluorescence image analysis. , 1988, The Journal of urology.

[24]  K. Chew,et al.  Nuclear DNA analysis of oral hyperplasia and dysplasia using image cytometry. , 1987, Journal of oral pathology.

[25]  W. Davenport,et al.  A diagnostic and epidemiologic survey of 15,783 oral lesions. , 1987, Journal of the American Dental Association.

[26]  P. Holmstrup Prognosis of oral cavity carcinomas , 1987 .

[27]  K. Sugimachi,et al.  Cytophotometric dna analysis of mucosal and submucosal carcinoma of the esophagus , 1984, Cancer.

[28]  T. Saku,et al.  Prediction of malignant change in oral precancerous lesions by DNA cytofluorometry , 1983 .

[29]  G. Shklar,et al.  The accuracy of the oral biopsy in the diagnosis of cancer. , 1969, Oral surgery, oral medicine, and oral pathology.

[30]  Sandler Hc Veterans Administration cooperative study of oral exfoliative cytology. , 1963 .

[31]  J.Edward Hall,et al.  Diagnostic cytology and its histopathologic Bases , 1962 .

[32]  G Haroske,et al.  Competence on demand in DNA image cytometry. , 2000, Pathology, research and practice.

[33]  A. Böcking,et al.  [Assessment of cervical dysplasia with DNA image cytometry]. , 1999, Der Pathologe.

[34]  A. Böcking,et al.  Abklärung zervikaler Dysplasien mittels DNA-Bild-Zytometrie , 1999, Der Pathologe.

[35]  G Haroske,et al.  1997 ESACP consensus report on diagnostic DNA image cytometry. Part II: Specific recommendations for quality assurance. European Society for Analytical Cellular Pathology. , 1998, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[36]  E. Eisenberg,et al.  The effect of clinical information on the histopathologic diagnosis of oral epithelial dysplasia. , 1998, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[37]  G Haroske,et al.  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. , 1998, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[38]  P. Wingo,et al.  Cancer statistics, 1997 , 1997, CA: a cancer journal for clinicians.

[39]  F Giroud,et al.  Consensus report of the ESACP task force on standardization of diagnostic DNA image cytometry. European Society for Analytical Cellular Pathology. , 1995, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[40]  C. Migliorati,et al.  The Cytobrush Plus cell collector in oral cytology. , 1994, Oral surgery, oral medicine, and oral pathology.

[41]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[42]  K. Christov,et al.  DNA content in reactive hyperplasia, precancerosis, and carcinomas of the oral cavity. A cytophotometric study. , 1984, Acta histochemica.

[43]  P. Stell,et al.  Early oral cancer: treatment by biopsy excision. , 1982, British Journal of Oral Surgery.

[44]  L. Sobin,et al.  Definition of leukoplakia and related lesions: an aid to studies on oral precancer. , 1978, Oral surgery, oral medicine, and oral pathology.

[45]  H. C. Sandler Veterans Administration cooperative study of oral exfoliative cytology. , 1963, Acta cytologica.

[46]  R. Feulgren,et al.  Mikroskopisch-chemischer Nachweis einer Nucleinsäure vom Typus der Thymonucleinsäure und die- darauf beruhende elektive Färbung von Zellkernen in mikroskopischen Präparaten. , 1924 .