The involvement of human papillomavirus for oral squamous cell carcinoma and precancerous lesion.

人乳头瘤病毒参与口腔鳞状细胞癌及癌前病变。

• 批准号: 04671090
• 负责人: AMEMIYA Akira
• 金额: $ 1.28万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671090/
• 关键词: HPV; Oral Squamous Cell Carcinoma; Normal Oral Epithelium; Lymph Node Metastasis; PCR; SSCP; p53; PCNA; 口腔扁平上皮癌; ヒトパピローマウイルス(HPV); 癌遺伝子

1) We investigated the prevalence rate of HPV DNAs in normal mucosa in the oral region. The nested PCR method was utilized to detect target DNA sequences using the HPV E6/E7 consensus primer pair. Of 56 patients examined, HPV 6 and HPV 16 DNA sequences were detected in a 46-year-old male and a 35-year-old female, respectively. These results suggest that HPVs are uncommon in normal oral epithelium.2) We examined 79 cases of oral squamous cell carcinoma (SCC) utilizing PCR and dot blot hybridization to detect HPV DNA.HPV-16 DNA was detected in 23 cases of oral SCC and both HPV-16 and HPV-18 DNA were detected in one case of tongue SCC.HPV-16DNA was identified predominantly in cancer cells which showed morphological resemblance to basal cells and reduced its hybridized signal in keratinized cells by in situ hybridization. Immunohistochemical detection of PCNA revealed that its close relationship to HPV-16 DNA identified cancer cells. These results suggest that HPV-16 DNA sequences might ha … More ve the ability to maintain the proliferative state of epithelial cells, and it may contribute to the production of malignant phenotype.3) Twenty cases of oral SCC with cervical lymph node metastasis were investigated for the involvement of HPV DNAs utilizing PCR and dot blot hybridization. HPV DNAs were detected in five cases. Four primary lesions contained HPV-16 DNA,and one contained both HPV-16 and HPV-18 DNAs out of 20 cases examined. The same types of HPV DNAs as those found in primary lesions were detected in metastatic lymph nodes including the one with HPV-16 and HPV-18.4) We examined 16 primary oral SCCs for detection of p53 mutations and HPV DNAs. Exon 5 through 8 of the p53 gene were examined using PCR-SSCP method. p53 mutations were observed in 4 cases (25.0%). HPV-DNA detection was performed using PCR with consensus primers. HPV-16 DNA was detected in 8 cases (50.0%). p53 mutation and HPV DNA were simultaneously detected in two intraosseus SCCs of the mandible.These finsings suggest that 1) genesis of oral SCC with HPV infection is different from HPV-negative SCCs ; 2) mutation of the p53 gene in HPV-positive cancer may be secondary event during tumor progression ; 3) inactivation of p53 function by mutation and/or HPV infection are one of important genetic events in the development of SCC in the oral cavity ; 4)other oncogenes or tumor suppressor genes may be crucial to prescribe poor prognosis in oral SCC. Less

1)调查口腔正常黏膜组织中HPVDNA的感染率。利用HPVE6/E7通用引物对，采用套式聚合酶链式反应方法检测靶DNA序列。在56名接受检查的患者中，分别在一名46岁的男性和一名35岁的女性身上检测到HPV6和HPV16DNA序列。2)应用聚合酶链式反应和斑点杂交技术检测79例口腔鳞癌组织中HPV-16DNA，其中23例口腔鳞癌组织中检测到HPV-16DNA，1例舌鳞癌组织中同时检测到HPV-16DNA和HPV-18DNA，原位杂交发现HPV-16DNA主要存在于癌细胞中，其形态与基底细胞相似，角化细胞中杂交信号减弱。免疫组织化学检测发现其与HPV-16DNA关系密切，可鉴定癌细胞。这些结果提示hpv-16dna序列可能具有…。3)应用聚合酶链式反应和斑点杂交技术对20例口腔鳞状细胞癌颈淋巴转移病例进行HPVDNA检测。5例HPVDNA阳性。在20例患者中，4例原发灶含有HPV-16DNA，1例同时含有HPV-16和HPV-18DNA。在转移淋巴结中检测到与原发灶相同类型的HPVDNA，包括HPV-16和HPV-18.4)我们检测了16例原发口腔鳞状细胞癌中P53突变和HPVDNA。用聚合酶链式反应-单链构象多态方法检测p53基因第5~8外显子。P53基因突变4例(25.0%)。HPV-DNA检测采用聚合酶链式反应。HPV-16DNA阳性8例(50.0%)。结论：1)HPV感染的口腔鳞癌的发生机制不同于HPV阴性的口腔鳞癌；2)HPV阳性的口腔鳞癌中P53基因突变可能是肿瘤进展过程中的次要事件；3)突变和/或HPV感染导致的P53功能失活是口腔鳞状细胞癌发生发展过程中的重要遗传事件之一；4)其他癌基因或抑癌基因可能是口腔鳞癌预后不良的重要因素。较少

项目成果

Itsuo Chiba et al.: "Mutation in the p53 gene and human papillomavirus infection in squamous cell carcinoma of the oral cavity." Preparing for publication to Oncogene.

Ituo Chiba 等人：“口腔鳞状细胞癌中的 p53 基因突变和人乳头瘤病毒感染。”

Motoaki Yasuda et al.: "Detection of papillomavirus genome in oral and their metastatic cervical lymph node tissues." Submitting to Journal of Oral Pathology and Medicine.

Motoaki Yasuda 等人：“口腔及其转移性颈淋巴结组织中乳头瘤病毒基因组的检测”。

Masanobu Shindoh: "The detection of human papillomavirus DNA sequences in normal oral scrapes by the nested PCR method using consensus primer pairs." Tumor Research. (投稿中).

Masanobu Shindoh：“使用共有引物对，通过巢式 PCR 方法检测正常口腔刮擦物中的人乳头瘤病毒 DNA 序列（目前正在提交）。”

Masanobu Shindoh et al.: "Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and its relationship to p53 and PCNA expression." Preparing for publication to Human Pathology.

Masanobu Shindoh 等人：“口腔鳞状细胞癌中人乳头瘤病毒 DNA 序列的检测及其与 p53 和 PCNA 表达的关系。”

Masanobu Shindoh: "Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and its relationship to p53 and PCNA expression." Human pathology. (投稿予定).

Masanobu Shindoh：“口腔鳞状细胞癌中人乳头瘤病毒 DNA 序列的检测及其与 p53 和 PCNA 表达的关系（待提交）。”