Li Wei, Wang Wei, Si Mani, Han Linfei, Gao Qinglei, Luo Aiyue, Li Yan, Lu Yunping, Wang Shixuan, Ma Ding
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China.
J Cancer Res Clin Oncol. 2008 Dec;134(12):1355-61. doi: 10.1007/s00432-008-0413-3. Epub 2008 May 14.
Integration of high-risk human papillomavirus (HR-HPVs) into the host DNA has been proposed as a risk for cervical carcinogenesis. HPV-16 is the predominant high-risk type and its integration ration varied largely in different cervical cancer (CC) samples. The aim of this study was to evaluate the correlation between physical state of HPV16 infection and extent of cervical lesion, as well as the clinical significance of virus existing state.
A total of 252 cases of paraffin-embedded blocks derived from cancer precursor lesion and cervical carcinoma samples were detected by HC-II for HR-HPV infection. HPV16 infection was confirmed by PCR and immunohistochemistry for HPV16 E7 simultaneously. The physical state of HPV16 infection were assessed by PCR for 3 overlapping fragments in E2 gene and multiple PCR for E2 gene and E7 gene.
The infection ratio of HR-HPV in normal cervical tissue, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cervical cancer were 15.0, 32.8, 54.3, 69.7, 93.8%, respectively. HR-HPV positive samples of 62.8% were infected with HPV16. The integration ratio of HPV16 in CIN III and cervical carcinoma were 35.7 and 58.1% respectively, both of which were significantly higher than that of CIN I and normal cervical tissues. The discrepancy was statistically significant (P < 0.05). Furthermore, it was observed that persistent virus infection and progression of cervical lesion were more common in CIN I with integrated HPV16 than that with episomal HPV16.
The integration ratio of HPV16 was accompanied by an increase in the grade of cervical lesion. The integrated state of HPV16 infection was strongly associated with persistent HPV infection and progression of cervical lesions.
高危型人乳头瘤病毒（HR-HPVs）整合入宿主DNA被认为是宫颈癌发生的一个风险因素。HPV-16是主要的高危型别，其整合率在不同宫颈癌（CC）样本中差异很大。本研究旨在评估HPV16感染的物理状态与宫颈病变程度之间的相关性，以及病毒存在状态的临床意义。
采用杂交捕获二代法（HC-II）检测252例来自癌前病变和宫颈癌样本的石蜡包埋组织块中的HR-HPV感染情况。同时通过PCR和HPV16 E7免疫组化确认HPV16感染。通过对E2基因的3个重叠片段进行PCR以及对E2基因和E7基因进行多重PCR来评估HPV16感染的物理状态。
正常宫颈组织、宫颈上皮内瘤变（CIN）I级、CIN II级、CIN III级和宫颈癌中HR-HPV的感染率分别为15.0%、32.8%、54.3%、69.7%、93.8%。62.8%的HR-HPV阳性样本感染了HPV16。HPV16在CIN III级和宫颈癌中的整合率分别为35.7%和58.1%，均显著高于CIN I级和正常宫颈组织。差异具有统计学意义（P<0.05）。此外，观察到HPV16整合型CIN I级中持续病毒感染和宫颈病变进展比游离型更常见。
HPV16的整合率随宫颈病变级别增加而升高。HPV16感染的整合状态与HPV持续感染和宫颈病变进展密切相关。
