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  • 學位論文

人類乳頭瘤病毒與口腔頰黏膜癌前病變的關係

Association of human papillomavirus with oral buccal mucosa premalignant lesions

指導教授 : 江俊斌

摘要


背景: 口腔頰黏膜鱗狀細胞癌是台灣最常見的口腔惡性腫瘤,其中嚼檳榔是頰黏膜癌最重要的致癌危險因子。然而先前的研究發現人類乳突瘤病毒感染,特別是高危險型人類乳突瘤病毒感染,可能在口腔鱗狀細胞癌,尤其是和口腔習慣不相關的口腔鱗狀細胞癌,致癌機轉中扮演重要的角色。 方法: 為了探討人類乳突瘤病毒在口腔頰黏膜癌致癌機轉上所扮演的角色,本實驗利用來自100個頰黏膜癌前病變標本,包括30 個上皮增生、25個疣狀增生、15個輕度上皮變異、16個中度上皮變異、14個重度上皮變異以及30個正常口腔黏膜(NOM)標本純化出的去氧核糖核酸 (DNA),利用巢式聚合酶鏈反應 (nested-PCR)、直接基因定序法,同時配合人類乳突瘤病毒基因晶片,來作人類乳突瘤病毒定型 (typing) 的工作,以此方法可在一次反應中偵測出39種不同人類乳突瘤病毒的基因型。研究不同口腔癌前病變疾病標本的人類乳突瘤病毒盛行率之外,本實驗也探討人類乳突瘤病毒感染與臨床病理參數間的關係,並以卡方檢定作統計分析。 結果: 本實驗發現,人類乳突瘤病毒在頰黏膜癌前病變標本的感染率 (21%) 與在正常口腔黏膜標本的感染率(20%),並無統計學上有意義的差異;如將頰黏膜癌前病變患者,分為有口腔習慣者與無口腔習慣者兩組後,無口腔習慣頰黏膜癌前病變的人類乳突病毒感染率 (30%, 8/27),高於有口腔習慣的頰黏膜癌前病變的人類乳突病毒感染率 (18%, 13/73),但此差異亦無統計學上的意義。人類乳突瘤病毒的陽性感染率與癌前病變組織型態 (P = 0.012) 及疾病進展 (P = 0.078) 有顯著相關,其中人類乳突瘤病毒感染較常出現於疣狀增生與重度上皮變異癌前病變。人類乳突瘤病毒陽性癌前病變的惡性轉變率 (62%, 13/21) 高於人類乳突瘤病毒陰性癌前病變的惡性轉變率 (39%, 31/79 ),其中高危險型人類乳突瘤病毒陽性癌前病變與多種人類乳突瘤病毒陽性癌前病變,具有較高的惡性轉變率,分別為 77.8% (7/9) 與 100% (3/3),低危險型人類乳突瘤病毒陽性癌前病變的惡性轉變率則為 33% (3/9)。高危險型與多種人類乳突瘤病毒陽性的癌前病變,具有較高機會惡化或惡性轉變 (P = 0.044)。 結論: 本實驗結果認為高危險型與多種的人類乳突瘤病毒感染,在頰黏膜癌前病變的惡性轉變過程中,扮演重要的角色,尤其是在口腔習慣不相關的頰黏膜癌前病變的惡性轉變過程中,扮演重要的角色。

並列摘要


Background Buccal squamous cell carcinoma (SCC) is the most common oral malignant tumor in Taiwan. Betel quid (BQ) chewing is the most important risk factor for the buccal mucosal carcinogenesis. Previous studies showed that human papillomaviruses (HPVs), particularly high-risk HPVs, play an important role in the development of oral SCCs (OSCCs), especially the non-oral habits (OH)-associated OSCCs. Materials and methods To evaluate the etiologic role of HPVs in buccal mucosal carcinogenesis, DNA samples were purified from 100 buccal premalignant lesions, including 30 hyperkeratosis, 25 verrucous hyperplasia, 15 mild dysplasia, 16 moderate dysplasia, and 14 severe dysplasia lesions, and 30 normal oral mucosa (NOM) specimens. A nested-polymerase chain reaction, DNA sequencing, and gene-chip HPV typing was used to detect 39 subtypes of HPV DNA in our samples. The HPV prevalence rates in different buccal premalignant groups and their correlation with clinicopathological parameters of patients with buccal premalignant lesions were analyzed by chi-square test. Results There was no significant difference in the overall HPV-positive rate between buccal premalignant lesion samples (21%) and NOM samples (20%). The overall HPV-positive rate was higher in non-OH-associated premalignant lesion samples (30%, 8/27) than in OH-associated premalignant lesion samples (18%, 13/73), although the difference was not significant. The HPV positivity was significantly associated with histological type of disease (P = 0.012) and disease progression (P = 0.078, marginal significance). HPV infection occurred more frequently in oral verrucous hyperplasia and severe dysplasia lesions than in other premalignant lesions. Moreover, the malignant transformation rate was higher in HPV-positive premalignant lesions (62%, 13/21) than in HPV-negative premalignant lesions (39%, 31/79). The malignant transformation rate was 78% (7/9) for premalignant lesions with high-risk HPV infection, 33% (3/9) for those with low-risk HPV infection, and 100% (3/3) for those with multiple HPV infections. Premalignant lesions with high-risk or multiple HPV infections had greater potential to become a more advanced premalignant lesion or a malignancy (P = 0.044). Conclusions High-risk and multiple HPV infections may play an important role in the transformation of a buccal premalignant lesion, especially a non-OH-associated buccal premalignant lesion, into an oral SCC.

參考文獻


Lee FH, Yen CY , Liu SY. Proliferative Verrucous Leukoplakia -A Preliminary Study. Chinese Journal of Oral and Maxillofacial Surgery 1998; 9: 47-58.
Wu CW, Chang KL, Chen HR, Chen CH , Shieh TY. Detection of Human Papillomavirus and Epstein- Barr Virus in Oral Squamous Cell Carcinoma by Using the Polymerase Chain Reaction Method. Taiwan Journal of Oral Medicine & Health Sciences 2002; 18: 17-26.
Lee JJ, Kok SH, Kuo YS, Yang PJ , Hahn LJ. Carcinoma of the Buccal Mucosa: A Representative Betel Nut Oral Cancer. Formosan Journal of Medicine 1997; 1: 638-647.
Chen GS , Chen CH. A Statistical Analysis of Oral Squamous Cell Carcinoma (Chinese). Kaohsiung J Med Sci 1995; 11: 582-588.
Castle PE, Schiffman M, Burk RD, Wacholder S, Hildesheim A, Herrero R, Bratti MC, Sherman ME , Lorincz A. Restricted cross-reactivity of hybrid capture 2 with nononcogenic human papillomavirus types. Cancer Epidemiol Biomarkers Prev 2002; 11: 1394-9.

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