口腔癌前病變惡性轉變相關之風險因子─台灣之世代研究

Abstract

背景 口腔癌前病變 (OPMDs) 指的是比正常口腔黏膜有較高可能發展成口腔鱗狀細胞癌(OSCC)之所有口腔病變。本實驗的目的是比較不同病理診斷之OPMD的自然發展過程，並希望能根據不同的病理診斷找出可有效減少發生惡性轉變的治療方法。 實驗方法 本實驗為一回溯性世代研究，病人來源1997年6月至2008年12月間來國立台灣大學附設醫院就診，並為經切片確診為OPMD者，其回診狀況記錄至2010年12月止。從病歷上記錄這些病人相關的臨床和病理學上的資料，如生日、性別、是否有抽菸、喝酒，及嚼食檳榔的習慣、臨床診斷，病理診斷，及接受過的治療。病理診斷之上皮變異程度以無變異、輕度、中度或重度上皮變異記之。欲觀察的結果為惡性腫瘤的發生。為避免已有口腔惡性腫瘤但在切片時未取樣到的狀況，病人在初次切片後六個月才會進入到研究的樣本之中。統計分析採用Kaplan–Meier estimates及Cox proportional hazard regression 來探討相關因子和惡性轉變時間的關係。 結果 本實驗的樣本數為2193人，其中以男性居多(84.5%)，有84.4%的人大於33歲。在OPMD的病理分類中，squamous hyperplasia是最常見的診斷(48.1%)，另外32.5%有上皮變異（分級為嚴重者有45人，中度者346人，輕度者321人）。在約13年的追蹤時間裡，168位病人（7.7%）發現有口腔癌。OPMD的組織學診斷和發生惡性轉變的時間在校正過後仍有相關性。診斷為疣狀增生（verrucous hyperplasia）或上皮變異程度為中度或重度者，其危險（hazard）較上皮無變異者為高（危險比分別為4.1、3.7，及5.2）。另接受手術刀切除OPMD者與未接受手術者相比，其惡性轉變的時間較長，其校正後的危險比為0.4。若再將OPMD的病人依病理診斷來分組，對無上皮變異、上皮變異程度為輕度到中度，及疣狀增生者而言，接受手術刀切除能有效的降低其與未接受手術者的危險比。 結論 OPMD可依據其惡性轉變時間之風險分為低危險組（包含無上皮變異及輕度上皮變異者）及高危險組（包含中度至重度上皮變異及疣狀增生者）。由於這兩組之患者都有在日後發展出口腔癌的危險，若將其手術切除能有效降低這兩組患者發生惡性轉變的風險比。

Background Oral potentially malignant disorders (OPMDs) were all clinical presentations that carry a risk of developing oral squamous cell carcinoma (OSCC). The aim of the study was to identify the natural history of OPMDs with different histological diagnosis, and correlate the outcome of malignant development with interventions corresponded to histological diagnosis in patient with OPMDs. Material and method The retrospective cohort study included patients with biopsy-confirmed OPMDs seen at National Taiwan University Hospital from July 1997 to June 2008 and followed until December 2010. The patients’ clinical and medical variables were identified from medical record, including date of birth, gender, personal habit, clinical presentation of OPMD, histological diagnosis with degree of epithelial dysplasia graded as none, mild, moderate or severe, and management. The outcome of interest was transformation to oral squamous cell carcinoma or oral verrucous carcinoma. To avoid co-existing malignancies, subjects were included 6 months after the date of the index biopsy. Kaplan–Meier estimates and Cox proportional hazard regression were undertaken to explore the simultaneous effects of multiple factors associated with transformation to oral cancer. Result There were 2193 patients included in the study. The majority of patients were men (84.5%), and 84.4% were over 33 years of age. Among all OPMDs, squamous hyperplasia was the most common histological diagnosis (48.1%), and 712 (32.5%) had oral epithelial dysplasia (45 severe, 346 moderate and 321 mild). One hundred and sixty-eight patients (7.7%) developed oral cancer over the follow-up period of 13 years. There was an association between histological diagnosis and time to transformation after adjustment. Patients with oral verrucous hyperplasia or moderate or severe dysplasia had higher hazard of transformation to oral cancer compared to those without dysplasia (HR were 4.1, 3.7, and 5.2, respectively). The association between blade surgery and time to transformation was also significant although attenuated (HR was 0.4). This significance of decreased hazard remained for patients who were diagnosed as having no dysplasia, mild to moderate dysplasia, and verrucous dysplasia. Conclusion OPMD lesions can be categorized as group with lower hazard (no dysplasia and mild dysplasia) and group with higher hazard (moderate to severe dysplasia and verrucous hyperplasia) to malignant transformation. Since both of them are at risk of developing cancer, blade surgery should be performed to reduce the hazard of malignant transformation.