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

1)我们调查了口腔正常粘膜中HPV DNA的患病率。采用HPVE 6/E7共有引物对，采用巢式PCR方法检测靶DNA序列。在56例接受检查的患者中，分别在一名46岁男性和一名35岁女性中检测到HPV 6和HPV 16 DNA序列。2）应用PCR和斑点杂交技术检测79例口腔鳞癌组织中HPV-16 DNA，其中23例口腔鳞癌组织中检出HPV-16，1例舌鳞癌组织中同时检出HPV-16和HPV-18。原位杂交结果显示16 DNA主要存在于癌细胞中，其形态与基底细胞相似，而在角化细胞中杂交信号减弱。PCNA免疫组化检测显示其与HPV-16 DNA关系密切，可作为癌细胞的鉴定标志。这些结果表明，HPV-16 DNA序列可能与HPV感染有关。 关于我们 3）应用聚合酶链反应（PCR）和斑点杂交技术检测20例口腔鳞癌颈淋巴结转移患者口腔鳞癌组织中HPVDNA的表达。其中5例检出HPV DNA。4例原发性病变含有HPV-16 DNA，1例同时含有HPV-16和HPV-18 DNA。4）对16例口腔鳞癌进行p53基因突变和HPV DNA检测。应用PCR-SSCP方法检测p53基因第5 ~ 8外显子。p53突变4例（25.0%）。HPV-DNA检测采用PCR方法，共有引物。HPV-16 DNA阳性8例（50.0%）。结果提示：1）口腔鳞癌伴HPV感染与HPV阴性SCC的发生不同，2）口腔鳞癌伴HPV阳性SCC中p53基因突变可能是肿瘤进展的继发事件，3）口腔鳞癌伴HPV阳性SCC中p53基因突变可能是肿瘤进展的继发事件。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关键因素。少

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