Dysplasia and DNA ploidy to prognosticate clinical outcome in oral potentially malignant disorders
Corresponding Author
Hans Prakash Sathasivam
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Cancer Research Centre, Institute for Medical Research, National Institute of Health, Setia Alam, Malaysia
Correspondence
Hans Prakash Sathasivam, Cancer Research Centre, Institute for Medical Research, National Institute of Health, 40170 Setia Alam, Malaysia.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorDeepa Nayar
King’s College London, Guy’s Hospital, London, UK
Contribution: Formal analysis, Investigation, Methodology, Resources, Writing - review & editing
Search for more papers by this authorPhilip Sloan
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Contribution: Formal analysis, Methodology, Project administration, Resources, Supervision, Writing - review & editing
Search for more papers by this authorPeter J. Thomson
Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Hong Kong
Contribution: Data curation, Investigation, Resources, Writing - review & editing
Search for more papers by this authorEdward W. Odell
King’s College London, Guy’s Hospital, London, UK
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Resources, Supervision, Writing - review & editing
Search for more papers by this authorMax Robinson
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Hans Prakash Sathasivam
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Cancer Research Centre, Institute for Medical Research, National Institute of Health, Setia Alam, Malaysia
Correspondence
Hans Prakash Sathasivam, Cancer Research Centre, Institute for Medical Research, National Institute of Health, 40170 Setia Alam, Malaysia.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorDeepa Nayar
King’s College London, Guy’s Hospital, London, UK
Contribution: Formal analysis, Investigation, Methodology, Resources, Writing - review & editing
Search for more papers by this authorPhilip Sloan
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Contribution: Formal analysis, Methodology, Project administration, Resources, Supervision, Writing - review & editing
Search for more papers by this authorPeter J. Thomson
Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Hong Kong
Contribution: Data curation, Investigation, Resources, Writing - review & editing
Search for more papers by this authorEdward W. Odell
King’s College London, Guy’s Hospital, London, UK
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Resources, Supervision, Writing - review & editing
Search for more papers by this authorMax Robinson
School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorAbstract
Background
Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes.
Methods
Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as “non-transforming” cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having “malignant transformation.”
Results
Ninety cases were included in the study. Seventy cases yielded informative DNA ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA ploidy status were both significantly associated with clinical outcome (P < 0.05). Severe dysplasia had a hazard ratio of 3.50 (CI: 1.46, 8.45; P = 0.005) compared to cases with mild dysplasia. Aneuploidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA ploidy status and 0.688 when DNA ploidy status was combined with dysplasia grading.
Conclusion
Our findings suggest that combining dysplasia grading with DNA ploidy status has clinical utility which could be used to develop novel management algorithms.
CONFLICTS OF INTEREST
The authors have no conflicts of interest to declare.
Supporting Information
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REFERENCES
- 1 AK El-Naggar, JKC Chan, JR Grandis, T Takata, PJ Slootweg, eds. WHO Classification of Head and Neck Tumours, 4th edn, Vol. 9. Lyon, France: International Agency for Research on Cancer; 2017. WHO Classification of Tumours.
- 2Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018; 125(6): 612-627.
- 3van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol. 2009; 45(4–5): 317-323.
- 4Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008; 37(1): 1-10.
- 5Sperandio M, Brown AL, Lock C, et al. Predictive value of dysplasia grading and DNA ploidy in malignant transformation of oral potentially malignant disorders. Cancer Prev Res (Phila). 2013; 6(8): 822-831.
- 6Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia – a systematic review and meta-analysis. Head Neck. 2009; 31(12): 1600-1609.
- 7Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008; 37(3): 127-133.
- 8Dost F, Le Cao K, Ford PJ, Ades C, Farah CS. Malignant transformation of oral epithelial dysplasia: a real-world evaluation of histopathologic grading. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014; 117(3): 343-352.
- 9Abbey LM, Kaugars GE, Gunsolley JC, et al. Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995; 80(2): 188-191.
- 10Fischer DJ, Epstein JB, Morton TH, Schwartz SM. Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med. 2004; 33(2): 65-70.
- 11Macey 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.
- 12Sen S. Aneuploidy and cancer. Curr Opin Oncol. 2000; 12(1): 82-88.
- 13Danielsen HE, Pradhan M, Novelli M. Revisiting tumour aneuploidy - the place of ploidy assessment in the molecular era. Nat Rev Clin Oncol. 2016; 13(5): 291-304.
- 14Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011; 11(1): 9-22.
- 15Duesberg P, Li R, Rasnick D, et al. Aneuploidy precedes and segregates with chemical carcinogenesis. Cancer Genet Cytogenet. 2000; 119(2): 83-93.
- 16Alaizari 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(2): 97-103.
- 17Haroske G, Baak JP, Danielsen H, et al. Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol. 2001; 23(2): 89-95.
- 18Brouns ER, Bloemena E, Belien JA, Broeckaert MA, Aartman IH, van der Waal I. DNA ploidy measurement in oral leukoplakia: different results between flow and image cytometry. Oral Oncol. 2012; 48(7): 636-640.
- 19Speight PM, Abram TJ, Floriano PN, et al. Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015; 120(4): 474-482 e472.
- 20Woo SB, Cashman EC, Lerman MA. Human papillomavirus-associated oral intraepithelial neoplasia. Mod Pathol. 2013; 26(10): 1288-1297.
- 21McCord C, Xu J, Xu W, et al. Association of high-risk human papillomavirus infection with oral epithelial dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 115(4): 541-549.
- 22Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer. 2010; 116(9): 2166-2173.
- 23Thomson PJ, Goodson ML, Smith DR. Profiling cancer risk in oral potentially malignant disorders-A patient cohort study. J Oral Pathol Med. 2017; 46(10): 888-895.
- 24Thomson PJ, Goodson ML, Cocks K, Turner JE. Interventional laser surgery for oral potentially malignant disorders: a longitudinal patient cohort study. Int J Oral Maxillofac Surg. 2017; 46(3): 337-342.
- 25Torres-Rendon A, Stewart R, Craig GT, Wells M, Speight PM. DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression. Oral Oncol. 2009; 45(6): 468-473.
- 26Bradley G, Odell EW, Raphael S, et al. Abnormal DNA content in oral epithelial dysplasia is associated with increased risk of progression to carcinoma. Br J Cancer. 2010; 103(9): 1432-1442.
- 27Bremmer JF, Brakenhoff RH, Broeckaert MA, et al. Prognostic value of DNA ploidy status in patients with oral leukoplakia. Oral Oncol. 2011; 47(10): 956-960.
- 28Siebers TJ, Bergshoeff VE, Otte-Holler I, et al. Chromosome instability predicts the progression of premalignant oral lesions. Oral Oncol. 2013; 49(12): 1121-1128.
- 29Pentenero M, Giaretti W, Navone R, et al. DNA aneuploidy and dysplasia in oral potentially malignant disorders: association with cigarette smoking and site. Oral Oncol. 2009; 45(10): 887-890.
- 30Donadini 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(5–6): 373-383.
- 31van Zyl AW, van Heerden MB, Langenegger E, van Heerden WF. Correlation between dysplasia and ploidy status in oral leukoplakia. Head Neck Pathol. 2012; 6(3): 322-327.
- 32Hald J, Overgaard J, Grau C. Evaluation of objective measures of smoking status–a prospective clinical study in a group of head and neck cancer patients treated with radiotherapy. Acta Oncol. 2003; 42(2): 154-159.
- 33Murray RP, Connett JE, Istvan JA, Nides MA, Rempel-Rossum S. Relations of cotinine and carbon monoxide to self-reported smoking in a cohort of smokers and ex-smokers followed over 5 years. Nicotine Tob Res. 2002; 4(3): 287-294.
- 34Khariwala SS, Carmella SG, Stepanov I, et al. Self-reported Tobacco use does not correlate with carcinogen exposure in smokers with head and neck cancer. Laryngoscope. 2015; 125(8): 1844-1848.
- 35Morales NA, Romano MA, Michael Cummings K, et al. Accuracy of self-reported tobacco use in newly diagnosed cancer patients. Cancer Causes Control. 2013; 24(6): 1223-1230.
- 36Warren GW, Arnold SM, Valentino JP, et al. Accuracy of self-reported tobacco assessments in a head and neck cancer treatment population. Radiother Oncol. 2012; 103(1): 45-48.
- 37Connor Gorber S, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M. The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res. 2009; 11(1): 12-24.
- 38Alberg AJ, Worley ML, Tooze JA, et al. The validity of self-reported recent smoking in head and neck cancer surgical patients. Otolaryngol Head Neck Surg. 2015; 153(6): 990-995.