脱落细胞DNA定量分析在口腔潜在恶性疾病诊断中的准确性
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摘要
目的:探讨口腔黏膜脱落细胞DNA定量分析在筛查口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)及口腔潜在恶性疾病(oral potential malignant disorders,OPMDs)的准确性。方法:对203例口腔黏膜病患者进行组织病理学检查和DNA定量分析检测,以组织病理学检查为金标准,评价DNA定量分析诊断的灵敏度、特异度、Youden指数、阳性似然比、阴性似然比、阳性预测值、阴性预测值等。结果:共纳入组织病理学检查为OSCC和原位癌(tumor in situ,TIS)的患者46例,白斑(oral leukoplakia,OLK)上皮异常增生患者39例,疣状白斑伴基底细胞增生活跃1例,白斑单纯增生29例,口腔扁平苔藓(oral lichen planus,OLP) 83例,炎症5例。以组织病理学诊断结果为金标准,以OSCC、TIS和上皮异常增生为阳性组,其他为阴性组,DNA定量分析系统诊断的灵敏度为79. 07%,特异度为81. 20%,准确度为80. 30%;诊断OSCC和TIS的灵敏度95. 65%,特异度81. 20%,诊断准确度为85. 28%;诊断上皮异常增生时,DNA定量分析系统诊断的灵敏度60. 00%,特异度81. 20%,诊断准确度为75. 8%。结论:DNA定量分析诊断操作微创,简便,可以作为OSCC及OPMDs的筛查方法以及OSCC术后随访的辅助监测手段。
Objective: To evaluate the diagnostic efficiency of oral mucosa disease,especially oral squamous cell carcinoma(OSCC) and oral potential malignant disorders(OPMDs) by DNA cytometry compared with histopathological diagnosis,so as to find a convenient,simple and low-invasive method for screening and follow-up. Methods: 203 subjects with OSCC,OPMDs and other oral mucosa disease without dysplasia according to the inclusion criteria and exclusion criteria were recruited from Peking University School and Hospital of Stomatology. The mean age was(52. 44 ± 13. 55) years,98 males and105 females. Brush biopsy was taken before scalpel biopsy at the same site. The brush biopsy sample was screened by moticytometer system for DNA cytometry after Feulgen stain,and histopathological examination were taken for the scalpel tissue. Data from DNA cytometry were used to calculate the parameters,such as sensitivity,specificity,positive and negative predictive values,odds ratios,Youden index(YI),positive and negative likelihood ratios,compared with the golden standard,histopathological diagnosis.DNA cytometry and histopathological diagnosis were performed back to back. Results: Totally,42 OSCC and 4 tumor in situ(TIS),39 oral leukoplakia(OLK) with dysplasia(17 mild dysplasia,13 medium dysplasia and 9 severe dysplasia),29 OLK with hyperplasia,1 verrucous OLK,83 oral lichen planus(OLP) and 5 inflammation were included in our research. We grouped the OSCC,TIS and dysplasia as the positive group and others without dysplasia as the negative group,the sensitivity of DNA cytometry was 79. 07%,the specificity was 81. 20%,and the diagnostic accuracy was 80. 30%,We grouped the OSCC and TIS as the tumor group,OLP,OLK with hyperplasia and inflammation as the non-tumor group,The sensitivity of DNA cytometry in diagnosing OSCC and TIS was 95. 65%,and the specificity was 81. 2%,The diagnostic accuracy was 85. 28%. positive predictive values 66. 67%,negative predictive values 97. 94%,ratio odds 95,positive likelihood ratio 5. 09,negative likelihood ratio 0. 05,and Youden index 0. 77. For the dysplasia,we grouped the different dysplasia together as the dyaplasia group,OLP,OLK with hyperplasia and inflammation as the non-tumor group,the sensitivity of DNA cytometry in diagnosing dyaplasia is 60%,the specificity is 81.2%. The diagnostic accuracy is 75. 8%,positive predictive values 52. 17%,negative predictive values 85. 59%,ratio odds 6. 48,positive likelihood ratio 3. 19,negative likelihood ratio 0. 49,and Youden index 0. 41. Conclusion: DNA cytometry is convenient and low-invasive,which can be used as an adjuvant method for screening the early OSCC and OPMDs,monitoring the prognosis of OSCC after surgery. Further large-scale and long period prospective studies are necessary to validate the better value of DNA cytometry.
Objective: To evaluate the diagnostic efficiency of oral mucosa disease,especially oral squamous cell carcinoma(OSCC) and oral potential malignant disorders(OPMDs) by DNA cytometry compared with histopathological diagnosis,so as to find a convenient,simple and low-invasive method for screening and follow-up. Methods: 203 subjects with OSCC,OPMDs and other oral mucosa disease without dysplasia according to the inclusion criteria and exclusion criteria were recruited from Peking University School and Hospital of Stomatology. The mean age was(52. 44 ± 13. 55) years,98 males and105 females. Brush biopsy was taken before scalpel biopsy at the same site. The brush biopsy sample was screened by moticytometer system for DNA cytometry after Feulgen stain,and histopathological examination were taken for the scalpel tissue. Data from DNA cytometry were used to calculate the parameters,such as sensitivity,specificity,positive and negative predictive values,odds ratios,Youden index(YI),positive and negative likelihood ratios,compared with the golden standard,histopathological diagnosis.DNA cytometry and histopathological diagnosis were performed back to back. Results: Totally,42 OSCC and 4 tumor in situ(TIS),39 oral leukoplakia(OLK) with dysplasia(17 mild dysplasia,13 medium dysplasia and 9 severe dysplasia),29 OLK with hyperplasia,1 verrucous OLK,83 oral lichen planus(OLP) and 5 inflammation were included in our research. We grouped the OSCC,TIS and dysplasia as the positive group and others without dysplasia as the negative group,the sensitivity of DNA cytometry was 79. 07%,the specificity was 81. 20%,and the diagnostic accuracy was 80. 30%,We grouped the OSCC and TIS as the tumor group,OLP,OLK with hyperplasia and inflammation as the non-tumor group,The sensitivity of DNA cytometry in diagnosing OSCC and TIS was 95. 65%,and the specificity was 81. 2%,The diagnostic accuracy was 85. 28%. positive predictive values 66. 67%,negative predictive values 97. 94%,ratio odds 95,positive likelihood ratio 5. 09,negative likelihood ratio 0. 05,and Youden index 0. 77. For the dysplasia,we grouped the different dysplasia together as the dyaplasia group,OLP,OLK with hyperplasia and inflammation as the non-tumor group,the sensitivity of DNA cytometry in diagnosing dyaplasia is 60%,the specificity is 81.2%. The diagnostic accuracy is 75. 8%,positive predictive values 52. 17%,negative predictive values 85. 59%,ratio odds 6. 48,positive likelihood ratio 3. 19,negative likelihood ratio 0. 49,and Youden index 0. 41. Conclusion: DNA cytometry is convenient and low-invasive,which can be used as an adjuvant method for screening the early OSCC and OPMDs,monitoring the prognosis of OSCC after surgery. Further large-scale and long period prospective studies are necessary to validate the better value of DNA cytometry.
引文
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[10] Warnakulasuriya KA,Johnson NW. Sensitivity and specificity of Ora Scan(R)toluidine blue mouthrinse in the detection of oral cancer and precancer[J]. J Oral Pathol Med,2010,25(3):97-103.
[11]曹婕,刘宏伟,刘晓松,等.口腔黏膜微核细胞数与上皮异常增生病损癌变的关系[J].北京大学学报(医学版),2011,43(4):600-602.
[12] Awan KH,Morgan PR,Warnakulasuriya S. Evaluation of an autofluorescence based imaging system(VELscopeTM)in the detection of oral potentially malignant disorders and benign keratoses[J]. Oral Oncol,2011,47(4):274-277.
[13]魏世蓉,王秋实,杨新,等.细胞DNA定量分析在尿脱落细胞学鉴别诊断中的应用[J].诊断病理学杂志,2018,25(4):285-288.
[14]张喆,孔令婷,孙寒雪,等.细胞DNA定量分析在宫颈病变筛查中的应用价值[J].中国医科大学学报,2017,46(11):1013-1018.
[15] Xiao X,Shi L,Li H,et al. DNA content status using brush biopsy with image cytometry correlated with staging of oral leukoplakia:a preliminary study[J]. Oral Oncol,2015,51(1):59-63.
[16] Liu Y,Li Y,Fu Y,et al. Quantitative prediction of oral cancer risk in patients with oral leukoplakia[J]. Oncotarget,2017,8(28):46057-46064.
[2] Zheng CM,Ge MH,Zhang SS,et al. Oral cavity cancer incidence and mortality in China,2010[J]. J Cancer Res Ther,2015,11(Suppl 2):149-154.
[3] Zeng H,Chen W,Zheng R,et al. Changing cancer survival in China during 2003-15:a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health,2018,6(5):e555-e567.
[4] Mello FW,Afp M,Dutra KL,et al. Prevalence of oral potentially malignant disorders:a systematic review and meta-analysis[J]. J Oral Pathol Med,2018,47(7):633-640.
[5] Carrard VC,van der Waal I. A clinical diagnosis of oral leukoplakia; a guide for dentists[J]. Med Oral Patol Oral Cir Bucal,2018,23(1):e59-e64.
[6] Smh A,Abushouk AI,Attia A,et al. Malignant transformation of oral lichen planus and oral lichenoid lesions:a meta-analysis of20095 patient data[J]. Oral Oncol,2017,68:92-102.
[7] Mehanna HM,Rattay T,Smith J,et al. Treatment and follow-up of oral dysplasia:a systematic review and meta-analysis[J].Head Neck,2009,31(12):1600-1609.
[8] Haroske G,Baak JP,Danielsen H,et al. Fourth updated ESACP consensus report on diagnostic DNA image cytometry[J]. Anal Cell Pathol,2001,23(2):89-95.
[9] Ma JM,Zhou TJ,Wang R,et al. Brush biopsy with DNA-image cytometry:a useful and noninvasive method for monitoring malignant transformation of potentially malignant oral disorders[J].Eur Arch Otorhinolaryngol,2014,271(12):3291-3295.
[10] Warnakulasuriya KA,Johnson NW. Sensitivity and specificity of Ora Scan(R)toluidine blue mouthrinse in the detection of oral cancer and precancer[J]. J Oral Pathol Med,2010,25(3):97-103.
[11]曹婕,刘宏伟,刘晓松,等.口腔黏膜微核细胞数与上皮异常增生病损癌变的关系[J].北京大学学报(医学版),2011,43(4):600-602.
[12] Awan KH,Morgan PR,Warnakulasuriya S. Evaluation of an autofluorescence based imaging system(VELscopeTM)in the detection of oral potentially malignant disorders and benign keratoses[J]. Oral Oncol,2011,47(4):274-277.
[13]魏世蓉,王秋实,杨新,等.细胞DNA定量分析在尿脱落细胞学鉴别诊断中的应用[J].诊断病理学杂志,2018,25(4):285-288.
[14]张喆,孔令婷,孙寒雪,等.细胞DNA定量分析在宫颈病变筛查中的应用价值[J].中国医科大学学报,2017,46(11):1013-1018.
[15] Xiao X,Shi L,Li H,et al. DNA content status using brush biopsy with image cytometry correlated with staging of oral leukoplakia:a preliminary study[J]. Oral Oncol,2015,51(1):59-63.
[16] Liu Y,Li Y,Fu Y,et al. Quantitative prediction of oral cancer risk in patients with oral leukoplakia[J]. Oncotarget,2017,8(28):46057-46064.
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