HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness

HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness
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DOI:
10.1002/jmv.10141
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发表时间:
2002-08-01
影响因子:
12.7
通讯作者:
Marcante, ML
Marcante, ML
中科院分区:
医学3区
文献类型:
--
作者:
Badaracco, G;Venuti, A;Marcante, ML

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将高危型HPV16和HPV18型整合到细胞基因组中被认为是恶性转化的重要步骤。对86例不同部位生殖器肿瘤,包括69例浸润性癌(包括5例微侵袭性癌)、9例原位癌、6例重度不典型增生和2例中度不典型增生,应用E6、E2和EL基因的类型特异性和多重聚合酶链式反应,研究了病毒的物理状态与临床病理参数的关系。HPV16阳性40例(46.6%),HPV18阳性7例(8.1%),两者均阳性39例(45.3%)。HPV16DNA既可作为单纯整合子(35.4%),也可作为单纯EB病毒(36.7%),或两者兼有(27.8%)。相反,46个含有HPV18的皮损均表现为单纯的完整形态。两型患者的健康状况与肿瘤部位、肿瘤/淋巴结/转移分期及组织分化程度无关。HPV16整合与侵袭性显著相关。有趣的是,在HPV16和HPV18共存的双重感染中,其基因组以异体形式出现的频率比在单一感染中更多,而在单一感染中,HPV16和HPV18并存时其基因组大多是整合的(P
The integration of the high-risk HPV16 and HPV18 types into the cell genome is considered an important step in malignant transformation. The relationship between the physical status of the virus and clinical/pathological parameters was studied by type-specific and multiplex PCR for E6, E2, and El sequences in 86 genital tumors from different sites, consisting of 69 invasive carcinomas (including 5 microinvasive carcinomas), 9 carcinomas in situ, 6 severe dysplasias, and 2 moderate dysplasias. Forty tumors contained HPV16 (46.6%), 7 HPV18 (8.1%), and 39 both viruses (45.3%). HPV16 DNA was found either as pure integrant (35.4%), or pure episome (36.7%), or a mixture of both (27.8%). Conversely, all 46 lesions containing HPV18 showed pure integrated forms. The physical status of both types was not related to the tumor site, the tumor/node/ metastasis stage, or the histological differentiation grade of the invasive carcinomas. HPV16 integration was significantly associated with invasiveness. Interestingly, in double infections when HPV16 coexisted with HPV18, its genome was found more frequently in episomal form than in single infections where, conversely, it was mostly integrated (P