口腔黏膜癌前病變的惡性轉變研究

Study of Malignant Transformation of Oral Mucosal Precancerous Lesions

陳百立(Pai-Li Chen)

指導教授 ： 謝天渝

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2006年)

https://doi.org/10.6832/KMU.2006.00107

摘要

研究目的
台灣地區口腔癌的發生率與死亡率因為嚼食檳榔的盛行而不斷上升。而口腔癌的發生是漸進性的，若能即早發現口腔出現癌前病變或癌前狀態時，能夠以較為保守的方式來加以治療並且密切追踪，應該可以減少之後產生惡性轉變的可能性，進而降低口腔癌的發生。本研究的目的在於了解常見的癌前病變或狀態發生的特性及其發生惡性轉變的機率，並探討對於癌前病變的外科手術治療及二氧化碳雷射治療是否能夠有效降低口腔癌前病變發生惡化的可能，並希望能從中找出針對口腔癌前病變適合的臨床追踪模式以期對口腔癌的發生能早期發現早期治療。
研究方法
研究對象是由高雄醫學大學附設中和紀念醫院口腔顎顎面外科門診自1986年至2003年因非口腔癌之口腔黏膜病變來院求診並接受切片及追踪治療的患者作回溯性研究，共計收集200位患者口腔中的548個病灶作為研究對象，針對患者的口腔習慣及每個病灶的初診日期、部位、臨床診斷及大小、所有的病理切片報告及所接受的治療、是否有產生惡性轉變及產生惡性轉變的日期等詳細紀錄。將病灶依病理報告分為上皮變異、疣狀增生、一般白斑症、口腔黏膜下維化等四類。將所收集的資料以卡方檢定、ANOVA、Kaplan-Meier存活分析等方法進行統計學分析。
結果
本研究所有病灶的平均追踪時間為35個月，病灶的發部位以頰黏膜為最多；而發生在舌的病灶發生惡性轉變的機率最高。所有病灶的每百人年惡性轉變率為4.09，而各類的病灶的每百人年惡性轉變率依次為上皮變異(7.97)、疣狀增生(5.91)、一般白斑症(3.51)、黏膜下纖維化症(3.01)。經過二氧化碳雷射治療的口腔癌前病變產生惡性轉變的比率有明顯的降低；而以一般外科手術來治療口腔癌前病變對於惡性轉變的發生雖有降低但是沒有統計學上明顯的差異。由每年的惡性轉變率差值分析可以發現所有的病灶在第一年的惡性轉變率差值最高，之後依序遞減，而到第三年之後的惡性轉變率差值有明顯降低；但是上皮變異的病灶前三年每年的惡性轉變率差值都是相同的。
結論
口腔癌前病變有以下的情形較容易發生惡性轉變：(1)病灶初診時患者年齡大於45歲 (2)病灶在顯微鏡下發現有上皮變異或疣狀增生 (3)發生在舌的病灶，因此對於這些病灶必須要更密切的追踪與積極的治療。而使用二氧化碳雷射來治療口腔癌前病灶可以有效減少病灶進一步產生惡性轉變的可能性。在發現病灶後的前三年內病灶發生惡性轉變的機會是最高的，因此對於口腔癌前病變的追踪前面三年必須要更密切而積極，以期能夠及早發現惡性轉變而能及早治療。之後會隨著時間增長而惡性轉變的可能性漸低，但是仍有可能會發生

關鍵字

口腔癌前病變 ； 惡性轉變 ； 口腔白斑症 ； 上皮變異 ； 二氧化碳雷射

並列摘要

Objective
As the areca quid consumption population is increasing in Taiwan , the incidence of and mortality from oral cavity cancer are climbing. The development of oral cavity cancer is a progressive procedure. Early detection of oral precancerous lesions or premalignant conditions with conservative treatment and close follow-up should decrease the possibility of subsequent malignant transformation of these lesions. The purposes of this study were
to discover the characteristic features of common oral precancerous lesions and premalignant conditions , to calculate out the malignant transformation rate of these lesions , to find out whether surgical treatment or CO2 laser therapy can reduce the malignant change of the these lesions ,and to work out a suitable clinical follow-up model for early detection and treatment of developing oral cavity cancer.
Patients & Methods
In the period 1986-2003 , patients with oral precancerous lesions diagnosed and received further biopsy and treatment in the Department of Oral and Maxillofacial Surgery at the Kaohsiung Medical University Chung-Ho Memorial Hospital were included in this study. The medical records of the lesions in these investigated patients were reviewed , and details including date of first visit , initial diagnosis, site, size, pathologic report , treatment and follow-up of these lesions , and risk factors of areca quid chewing , cigarette smoking , alcohol consumption, and the date and prognosis of malignant transformation were all collected and recorded. All the lesions were categorized by their pathologic reports into four groups : epithelial dysplasia, verrucous hyperplasia, leukoplakia without dysplasia , and oral submucous fibrosis. All data collected were statically analyzed with chi-square test, ANOVA, Kaplan-Meier survival analysis.
Results
Five hundred and forty-eight lesions were enrolled in this study. The mean follow-up time of all lesions was 35 months. More than two thirds of the lesions occurred on the buccal mucosa .The lesions on the tongue had the highest malignant transformation rate. The overall malignant transformation rate in one-hundred person-year of all lesions was 4.09. The malignant transformation rates in one-hundred person-year of epithelial dysplasia , verrucous hyperplasia, leukoplakia without dysplasia , and oral submucous fibrosis are 7.97, 5.91, 3.51, and 3.01 respectively . There was a statically significant decrease in the malignant transformation rate of the lesions receiving carbon dioxide laser therapy. However, there was no statically significant decrease in the malignant transformation rate of the precancerous lesions treated by conventional surgical excision. There was the highest annual difference in the malignant transformation of all lesions in the first year after diagnosis. The annual difference decreased gradually every year and drops remarkably three years later. However, the lesions with epithelial dysplasia had the same annual difference in the malignant transformation rate in the first three years follow-up.
Conclusions
The oral precancerous lesions in patients with the age above 45 year old, with epithelial dysplasia or verrucous hyperplasia without epithelial dysplasia , but on the lateral border of the tongue had the higher malignant transformation rate. The lesions with those risky conditions need more close follow-up and aggressive treatment. Carbon dioxide laser therapy is effective to prevent further malignant transformation of the oral precancerous lesions. All oral precancerous lesions need more close follow-up to monitor the malignant change tendency in the first three years after diagnosis. Although the malignant transformation rate of the precancerous lesions decreases three years after the diagnosis, there are still a few cases that develop oral cavity cancer after three years of follow-up .

並列關鍵字

oral precancerous lesions ； malignant transformation ； oral leukoplakia ； epithelial dysplasia ； carbon dioxide laser therapy

參考文獻

1. IARC: Betel-quid and areca-nut chewing. International Agency for Research on Cancer Monographs 37 , Lyon, 1986

2. Ko YC, Huang YL, Lee CH, et al: Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 24:450-3, 1995

3. Betel-Quid and Areca-Nut Chewing and Some Related Nitrosamines. IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans 85:11-18, 2003

4. Jacob BJ, Straif K, Thomas G, et al: Betel quid without tobacco as a risk factor for oral precancers. Oral Oncol 40:697-704, 2004

5. Lo WL, Kao SY, Chi LY, et al: Outcomes of oral squamous cell carcinoma in Taiwan after surgical therapy: factors affecting survival. J Oral Maxillofac Surg 61:751-8, 2003