Viral load, E2 gene disruption status, and lineage of human papillomavirus type 16 infection in cervical neoplasia
Viral load, E2 gene disruption status, and lineage of human papillomavirus type 16 infection in cervical neoplasia
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DOI：
10.1086/509622
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发表时间：
2006-12-15
影响因子：
6.4
通讯作者：
Chan, Paul K. S.
中科院分区：
文献类型：
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作者：
Cheung, Jo L. K.;Lo, Keith W. K.;Chan, Paul K. S.
人乳头瘤病毒（HPV）载量和整合状态的临床效用仍不清楚。我们应用精确的方法描述了104例HPV-16单型感染妇女的病毒载量、整合状态和谱系，包括19例正常宫颈，9例组织学证实的宫颈上皮内瘤变（CIN）1，24例CIN 2，27例CIN 3和25例鳞状细胞癌（SCC）。较高的粗病毒载量，通过实时聚合酶链反应（PCR）靶向E7基因，观察到SCC，但变得微不足道后，细胞含量的标准化。通过分别靶向E2基因的羧基、氨基和铰链结构域的实时PCR定位和定量整合。在所有疾病组中观察到纯游离型、整合型和混合型。大多数E2基因破坏涉及氨基末端，但保留了铰链区，该铰链区经常被用作整合的替代标记。仅在CIN 3和SCC组中观察到涉及所有3个E2区域的大片段破坏。总的来说，33.3%的CIN 3组和28.0%的SCC组含有纯附加型基因组。亚洲血统与CIN 3/SCC的风险高于欧洲血统，7例大片段E2破坏中有6例来自亚洲血统。病毒谱系、整合模式和肿瘤发生之间的联系值得进一步研究。
The clinical utility of human papillomavirus (HPV) load and integration status remains unclear. We applied refined methods to delineate the viral load, integration status, and lineage of 104 women with HPV-16 monotype infection, including 19 with normal cervices, 9 with histologically proven cervical intraepithelial neoplasia (CIN) 1, 24 with CIN 2, 27 with CIN 3, and 25 with squamous cell carcinoma (SCC). Higher crude viral load, as determined by real-time polymerase chain reaction (PCR) targeting the E7 gene, was observed for SCC but became insignificant after normalization for cell content. Integration was located and quantified by real-time PCRs targeting, respectively, the carboxyl, amino, and hinge domains of the E2 gene. Pure episomal, integrated, and mixed forms were observed in all disease groups. Most E2 gene disruptions involved the amino-terminal, but sparing the hinge region that has been frequently used as a surrogate marker of integration. Large-fragment disruption involving all 3 E2 regions was observed only in the CIN 3 and SCC groups. Altogether, 33.3% of the CIN 3 group and 28.0% of the SCC group harbored pure episomal genomes. The Asian lineage was associated with a higher risk for CIN 3/SCC than the European lineage, and 6 of the 7 large-fragment E2 disruptions were from Asian lineage. The link between viral lineage, integration pattern, and oncogenesis deserves further study.