宫颈癌HPV18 E6直接相互作用蛋白的筛选及相关功能效应验证
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摘要
目的：HPV18 E6癌蛋白与宫颈癌发生、发展密切相关。应用酵母双杂交系统，构建HPV18E6癌蛋白诱饵质粒，在Hela细胞cDNA文库中筛选与HPV18 E6癌基因直接相互结合蛋白，并对TMEM 87B进行生物信息学分析，探讨HPV18 E6和vimentin直接相互作用在顺铂诱导宫颈癌细胞衰老中的功能效应。
方法：
1．应用RT PCR扩增HPV18E6基因cDNA开放阅读框基因片段后与pGBKT7载体定向重组，通过酶切测序鉴定重组质粒；醋酸锂法将pGBKT7-HPV18 E6重组质粒转化AH109酵母菌株，缺陷性培养基上观察AH109生长情况，检测诱饵载体有无毒性作用和单倍体及二倍体自激活效应。
2．将成功构建的pGBKT7-HPV18E6重组质粒醋酸锂法转化感受态酵母菌AH109，随后转化Hela MATCHMAKER cDNA文库质粒，筛选阳性克隆。提取酵母质粒纯化后电转感受态大肠杆菌DH5α，提取阳性质粒，排除假阳性和重复插入片段后酶切电泳、测序后行基因序列分析宫颈癌HPV18 E6直接相互作用蛋白。
3．应用因特网资源，运用BLAST、ProtParam tool、The ELM Server及InterProScan等数据库或在线软件对TMEM 87B基因及其编码蛋白进行生物信息学分析，预测其基因结构、染色体定位、编码蛋白质理化性质、亚细胞定位、蛋白质功能域等信息，并对多物种中的相似性蛋白进行了系统进化分析。
4．酵母体内和体外Co-IP法验证HPV18 E6和vimentin直接相互作用；免疫组化法检测HPV18 E6和vimentin蛋白及CBX3蛋白在人宫颈癌切片中的表达情况。应用不同浓度梯度顺铂作用Hela细胞，选择最佳诱导衰老而无明显凋亡发生的实验浓度。检测Hela细胞衰老过程中HPV18 E6和vimentin以及P53、P21、CDC2等衰老相关调控基因表达变化；应用SA-βG al(衰老相关β-半乳糖苷酶)染色法检测通过脂质体法单独转染或共转染siRNA-HPV18 E6和siRNA-vimentin时顺铂诱导肿瘤细胞衰老敏感性变化情况；PI单染流式细胞仪检测细胞周期变化；Western blot检测P53、P21、CDC2等衰老相关调控基因表达变化情况；建立顺铂诱导宫颈癌肿瘤细胞衰老动物模型；分析衰老动物模型中HPV18 E6和vimentin表达变化。
结果：
1．成功构建重组质粒pGBKT7-HPV18 E6，转化重组质粒pGBKT7-HPV18 E6和pGBKT7空载体的酵母菌在YPDA液体培养基中培养16h后，菌液的A600nm值分别为0．98和0．99；两种酵母菌均在SD／-Trp／X-α-gal平板上长出白色菌落，在SD／-His／-Trp／X-α-gal，SD／-Ade／-Trp／X-α-gal平板上不能生长，pGBKT7-HPV18E6转化酵母菌AH109与pGADT7-T转化酵母菌Y187交配后二倍体在SD／-Trp／-Leu培养盘中能长出白色克隆，而在SD／-His／-Trp／-Leu／X-α-gal及SD／-Ade／-His／-Trp／-Leu／X-α-gal盘中均无克隆生长，说明重组质粒pGBKT7-HPV18E6对酵母菌AH109无毒性且不具自主激活报告基因效应。
2．该诱饵载体应用于在Hela细胞cDNA文库中筛选与HPV18E6相互作用的蛋白质，随机挑取50个克隆进行电转后，双酶切后电泳，测序鉴定7种与HPV18E6直接相互作用蛋白：跨膜蛋白87B、膦甲酸免疫相关蛋白5、波形蛋白Vimentin、KM-HN-1蛋白、无功能糖基转移酶样蛋白7、痘苗相关激酶蛋白2以及一种未知蛋白。
3．对获得的7种阳性蛋白进行初步生物信息学分析确定其生物功能，对TMEM 87B蛋白进行进一步分析，发现TMEM87B是一种6次跨膜的分泌性蛋白，有众多磷酸化位点和功能基序，在多物种间有高度保守序列，与肿瘤生成信号转导和转录调控相关；
4．免疫组化结果显示CBX3在CIN和宫颈癌早期表达达高峰，而HPV18 E6和vimentin在宫颈癌早期呈高表达。在一定小剂量顺铂(3．300μM)诱导下，Hela细胞呈现衰老表型，细胞变大变扁平，胞浆空泡增多，SA-βGal染色呈阳性着色，细胞周期阻滞在G2／M期，细胞调亡不明显，P53、P21、P-CDC2基因在顺铂诱导衰老过程中表达增强。分别转染50nM siRNA-vimentin和50nM siRNA-HPV 18 E6后，增敏顺铂(1．650μM)诱导Hela细胞衰老(P＜0．05)；共转染50nM siRNA-vimentin和50nM siRNA-HPV18 E6后，Hela细胞衰老率增加，且增敏顺铂(0．825μM)诱导Hela细胞衰老(P＜0．05)。衰老细胞变大、变园、扁平，衰老相关β-半乳糖苷酶染色阳性；细胞周期G2／M期阻滞；vimentin、P53、CDC-2表达上调，HPV 18 E6表达下调。
结论：七种与HPV18E6相互作用的蛋白质可能是潜在的宫颈癌检测指标。TMEM87B是一种6次跨膜的分泌性蛋白，可能与肿瘤生成信号转导和转录调控相关；HPV18 E6和vimentin直接相互作用可能抵抗了顺铂诱导宫颈癌细胞衰老。
Subject: High-risk human papillomaviruses oncoprotein 18 E6 (HPV18 E6) is associatedwith cervix cancer. The study was conducted to screen for novel binding proteinsinteracting with high-risk HPV 18 E6 oncogene, to identify Transmembrane Protein 87B(TMEM 87B) as a novel binding protein interacting with HPV 18-E6 oncoprotein andperform an initial bioinformatics analysis, and to explore the effects of the direct interactionbetween HPV 18 E6 and vimentin on the senescence induced by DDP.
Methods:
1. The strain AH109 was transformed with pGBKT7-HPV18 E6 plasmid, and subsequenttransference was utilized to screen for interacting proteins with HPV 18 E6 in humanHela cDNA library.
2. The yeast strain AH109 was transformed with pGBKT7-HPV 18 E6, and the yeastmating assay was utilized to identify the interaction between TMEM 87B and HPV18E6 in human Hela cDNA library.
3. TMEM87B gene structure, genomic localization, the physical and chemicalcharacteristics, subcellular localization, functional domain were predicted, as well as thesystematic evolution analysis on the similar proteins among several species.
4. The yeast strain AH109 was transformed with pGBKT7-HPV 18 E6, and the yeastmating assay was utilized to identify the interaction between vimentin and HPV18 E6in human Hela cDNA library. The expression of CBX3, HPV18 E6 and vimentin weredetected in the tissues of cervical infection, CIN and cervical cancer by use of immunohistochemistry. Cisplatin with different concentrations were applied in tumourcells, and to choose the suitable concentration when the senescence rate was highestwithout obvious apoptosis. The cell senescence rates of tumour cells induced bycisplatin were detected by using of SA-βGal staining method.
5. The expression and activity of P53, P21 and P-CDC2 genes changed obviously duringthe senescence process. The senescence sensitivity of Hela cells induced by cisplatin(1.650μM) was increase after the transfection of 50nM siRNA-vimentin and 50nMsiRNA-HPV, while the senescence sensitivity of Hela cells induced by cisplatin (0. 825μM)was increase after the co-transfection(P＜0.05). The senescent Hela cells inducedby DDP become large and flatten, positive staining of SA-β-Gal. PI staining methodwas used to test the cell cycle. The expression of senescence regulating genes such asP53, P21 and Cdc2 were detected by using of western blot. The senescence aminalmodel was established and the expression of HPV18 E6 and vimentin was tested.
Results:
1. In yeast two-hybrid assay, HPV18 E6 mRNA was expressed and there was noself-activation and toxicity in strain AH 109.
2. Seven proteins that interacted with HPV18 E6, including transmembrane protein 87B,phosphonoformate immuno-associated protein 5, vimentin, KM-HN-1 protein,dedicator of cytokinesis 7, vaccinia related kinase 2 and a hypothetical protein, wereidentified. It was suggested that yeast two-hybrid system is an efficient for screeninginteracting proteins. The high-risk HPV 18 E6 oncogene may interact with the proteins,which may be associated with signal transduction and transcriptional control, epithelialcell invasion and migration, as well as humoral and cellular immune etc.
3. The special TMEM 87B mRNA expression was detected in Hela cells, and the blueclones were validated in the yeast mating assay. Efficient bioinformatics analysis hasfundamentally identified that TMEM 87B is a secretary protein, containing many phosphorylation sites and functional motifs, and may be involved in signal transductionand transcriptional control in carcinogenesis. It has been indicated that the yeasttwo-hybrid system is an efficient for screening interacting proteins.
4. The expression of CBX3 reaches its peak in the tissues of CIN and cervical cancer inthe early stage, while the over-expression of HPV18 E6 and vimentin were detected inthe tissues of cervical cancer in the early stage. The senescent Hela cells induced byDDP (3.300μM) become large and flatten, increased vacuolus in cytoplasm, positivestaining of SA-β-Gal. The senescent cells were mainly blocked during G2/M period andapoptosis was not obvious. The expression and activity of P53, P21 and P-CDC2 geneschanged obviously during the senescence process. The senescence sensitivity of Helacells induced by cisplatin (1.650μM) was increase after the transfection of 50nMsiRNA-vimentin and 50nM siRNA-HPV, while the senescence sensitivity of Hela cellsinduced by cisplatin (0.825μM) was increase after the co-transfection (P＜0.05). Thesenescent Hela cells induced by DDP become large and flatten, positive staining ofSA-β-Gal.
Conclusion: This investigation provides functional clues for further exploration of potentialoncogenesis targets for cancer biotherapy. The novel gene TMEM 87B may interact withHPV18 E6, and maybe a potential oncogenesis target according to bioinformatics analysis.The direct interaction between HPV18 E6 and vimentin plays an important role in thesenescence induced by DDP.
方法：
1．应用RT PCR扩增HPV18E6基因cDNA开放阅读框基因片段后与pGBKT7载体定向重组，通过酶切测序鉴定重组质粒；醋酸锂法将pGBKT7-HPV18 E6重组质粒转化AH109酵母菌株，缺陷性培养基上观察AH109生长情况，检测诱饵载体有无毒性作用和单倍体及二倍体自激活效应。
2．将成功构建的pGBKT7-HPV18E6重组质粒醋酸锂法转化感受态酵母菌AH109，随后转化Hela MATCHMAKER cDNA文库质粒，筛选阳性克隆。提取酵母质粒纯化后电转感受态大肠杆菌DH5α，提取阳性质粒，排除假阳性和重复插入片段后酶切电泳、测序后行基因序列分析宫颈癌HPV18 E6直接相互作用蛋白。
3．应用因特网资源，运用BLAST、ProtParam tool、The ELM Server及InterProScan等数据库或在线软件对TMEM 87B基因及其编码蛋白进行生物信息学分析，预测其基因结构、染色体定位、编码蛋白质理化性质、亚细胞定位、蛋白质功能域等信息，并对多物种中的相似性蛋白进行了系统进化分析。
4．酵母体内和体外Co-IP法验证HPV18 E6和vimentin直接相互作用；免疫组化法检测HPV18 E6和vimentin蛋白及CBX3蛋白在人宫颈癌切片中的表达情况。应用不同浓度梯度顺铂作用Hela细胞，选择最佳诱导衰老而无明显凋亡发生的实验浓度。检测Hela细胞衰老过程中HPV18 E6和vimentin以及P53、P21、CDC2等衰老相关调控基因表达变化；应用SA-βG al(衰老相关β-半乳糖苷酶)染色法检测通过脂质体法单独转染或共转染siRNA-HPV18 E6和siRNA-vimentin时顺铂诱导肿瘤细胞衰老敏感性变化情况；PI单染流式细胞仪检测细胞周期变化；Western blot检测P53、P21、CDC2等衰老相关调控基因表达变化情况；建立顺铂诱导宫颈癌肿瘤细胞衰老动物模型；分析衰老动物模型中HPV18 E6和vimentin表达变化。
结果：
1．成功构建重组质粒pGBKT7-HPV18 E6，转化重组质粒pGBKT7-HPV18 E6和pGBKT7空载体的酵母菌在YPDA液体培养基中培养16h后，菌液的A600nm值分别为0．98和0．99；两种酵母菌均在SD／-Trp／X-α-gal平板上长出白色菌落，在SD／-His／-Trp／X-α-gal，SD／-Ade／-Trp／X-α-gal平板上不能生长，pGBKT7-HPV18E6转化酵母菌AH109与pGADT7-T转化酵母菌Y187交配后二倍体在SD／-Trp／-Leu培养盘中能长出白色克隆，而在SD／-His／-Trp／-Leu／X-α-gal及SD／-Ade／-His／-Trp／-Leu／X-α-gal盘中均无克隆生长，说明重组质粒pGBKT7-HPV18E6对酵母菌AH109无毒性且不具自主激活报告基因效应。
2．该诱饵载体应用于在Hela细胞cDNA文库中筛选与HPV18E6相互作用的蛋白质，随机挑取50个克隆进行电转后，双酶切后电泳，测序鉴定7种与HPV18E6直接相互作用蛋白：跨膜蛋白87B、膦甲酸免疫相关蛋白5、波形蛋白Vimentin、KM-HN-1蛋白、无功能糖基转移酶样蛋白7、痘苗相关激酶蛋白2以及一种未知蛋白。
3．对获得的7种阳性蛋白进行初步生物信息学分析确定其生物功能，对TMEM 87B蛋白进行进一步分析，发现TMEM87B是一种6次跨膜的分泌性蛋白，有众多磷酸化位点和功能基序，在多物种间有高度保守序列，与肿瘤生成信号转导和转录调控相关；
4．免疫组化结果显示CBX3在CIN和宫颈癌早期表达达高峰，而HPV18 E6和vimentin在宫颈癌早期呈高表达。在一定小剂量顺铂(3．300μM)诱导下，Hela细胞呈现衰老表型，细胞变大变扁平，胞浆空泡增多，SA-βGal染色呈阳性着色，细胞周期阻滞在G2／M期，细胞调亡不明显，P53、P21、P-CDC2基因在顺铂诱导衰老过程中表达增强。分别转染50nM siRNA-vimentin和50nM siRNA-HPV 18 E6后，增敏顺铂(1．650μM)诱导Hela细胞衰老(P＜0．05)；共转染50nM siRNA-vimentin和50nM siRNA-HPV18 E6后，Hela细胞衰老率增加，且增敏顺铂(0．825μM)诱导Hela细胞衰老(P＜0．05)。衰老细胞变大、变园、扁平，衰老相关β-半乳糖苷酶染色阳性；细胞周期G2／M期阻滞；vimentin、P53、CDC-2表达上调，HPV 18 E6表达下调。
结论：七种与HPV18E6相互作用的蛋白质可能是潜在的宫颈癌检测指标。TMEM87B是一种6次跨膜的分泌性蛋白，可能与肿瘤生成信号转导和转录调控相关；HPV18 E6和vimentin直接相互作用可能抵抗了顺铂诱导宫颈癌细胞衰老。
Subject: High-risk human papillomaviruses oncoprotein 18 E6 (HPV18 E6) is associatedwith cervix cancer. The study was conducted to screen for novel binding proteinsinteracting with high-risk HPV 18 E6 oncogene, to identify Transmembrane Protein 87B(TMEM 87B) as a novel binding protein interacting with HPV 18-E6 oncoprotein andperform an initial bioinformatics analysis, and to explore the effects of the direct interactionbetween HPV 18 E6 and vimentin on the senescence induced by DDP.
Methods:
1. The strain AH109 was transformed with pGBKT7-HPV18 E6 plasmid, and subsequenttransference was utilized to screen for interacting proteins with HPV 18 E6 in humanHela cDNA library.
2. The yeast strain AH109 was transformed with pGBKT7-HPV 18 E6, and the yeastmating assay was utilized to identify the interaction between TMEM 87B and HPV18E6 in human Hela cDNA library.
3. TMEM87B gene structure, genomic localization, the physical and chemicalcharacteristics, subcellular localization, functional domain were predicted, as well as thesystematic evolution analysis on the similar proteins among several species.
4. The yeast strain AH109 was transformed with pGBKT7-HPV 18 E6, and the yeastmating assay was utilized to identify the interaction between vimentin and HPV18 E6in human Hela cDNA library. The expression of CBX3, HPV18 E6 and vimentin weredetected in the tissues of cervical infection, CIN and cervical cancer by use of immunohistochemistry. Cisplatin with different concentrations were applied in tumourcells, and to choose the suitable concentration when the senescence rate was highestwithout obvious apoptosis. The cell senescence rates of tumour cells induced bycisplatin were detected by using of SA-βGal staining method.
5. The expression and activity of P53, P21 and P-CDC2 genes changed obviously duringthe senescence process. The senescence sensitivity of Hela cells induced by cisplatin(1.650μM) was increase after the transfection of 50nM siRNA-vimentin and 50nMsiRNA-HPV, while the senescence sensitivity of Hela cells induced by cisplatin (0. 825μM)was increase after the co-transfection(P＜0.05). The senescent Hela cells inducedby DDP become large and flatten, positive staining of SA-β-Gal. PI staining methodwas used to test the cell cycle. The expression of senescence regulating genes such asP53, P21 and Cdc2 were detected by using of western blot. The senescence aminalmodel was established and the expression of HPV18 E6 and vimentin was tested.
Results:
1. In yeast two-hybrid assay, HPV18 E6 mRNA was expressed and there was noself-activation and toxicity in strain AH 109.
2. Seven proteins that interacted with HPV18 E6, including transmembrane protein 87B,phosphonoformate immuno-associated protein 5, vimentin, KM-HN-1 protein,dedicator of cytokinesis 7, vaccinia related kinase 2 and a hypothetical protein, wereidentified. It was suggested that yeast two-hybrid system is an efficient for screeninginteracting proteins. The high-risk HPV 18 E6 oncogene may interact with the proteins,which may be associated with signal transduction and transcriptional control, epithelialcell invasion and migration, as well as humoral and cellular immune etc.
3. The special TMEM 87B mRNA expression was detected in Hela cells, and the blueclones were validated in the yeast mating assay. Efficient bioinformatics analysis hasfundamentally identified that TMEM 87B is a secretary protein, containing many phosphorylation sites and functional motifs, and may be involved in signal transductionand transcriptional control in carcinogenesis. It has been indicated that the yeasttwo-hybrid system is an efficient for screening interacting proteins.
4. The expression of CBX3 reaches its peak in the tissues of CIN and cervical cancer inthe early stage, while the over-expression of HPV18 E6 and vimentin were detected inthe tissues of cervical cancer in the early stage. The senescent Hela cells induced byDDP (3.300μM) become large and flatten, increased vacuolus in cytoplasm, positivestaining of SA-β-Gal. The senescent cells were mainly blocked during G2/M period andapoptosis was not obvious. The expression and activity of P53, P21 and P-CDC2 geneschanged obviously during the senescence process. The senescence sensitivity of Helacells induced by cisplatin (1.650μM) was increase after the transfection of 50nMsiRNA-vimentin and 50nM siRNA-HPV, while the senescence sensitivity of Hela cellsinduced by cisplatin (0.825μM) was increase after the co-transfection (P＜0.05). Thesenescent Hela cells induced by DDP become large and flatten, positive staining ofSA-β-Gal.
Conclusion: This investigation provides functional clues for further exploration of potentialoncogenesis targets for cancer biotherapy. The novel gene TMEM 87B may interact withHPV18 E6, and maybe a potential oncogenesis target according to bioinformatics analysis.The direct interaction between HPV18 E6 and vimentin plays an important role in thesenescence induced by DDP.
引文
1. Zur hausen h. Papillomavimses and cancer: from basic studies to clinical application [J].Nat Rev Cancer, 2002, 2: 342-350.
2. Nirchio V, Lipsi R, Fusilli S, et al. HPV infection: comparison between morphological studies and molecular biology [J].Pathologica, 2008, 100 (3): 149-155.
3. Ding B, Chi SG, Kim Sh, et al. Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following h2O2 exposure[J].J Cell Sci, 2007; 1; 120(13):2284-2294.
4. Scheffher, M., B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136, 1990.
5. Nomine Y, Masson M, Charbonnier S, et al.Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis [J]. Mol Cell, 2006, 21(5): 665-678.
6. Zur Hausen, H: Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst 92:690-698, 2000.
7. Zur Hausen, H: Viruses in human cancers. Eur. J. Cancer 35:1878-1885, 1999.
8. Subramanya D, Grivas PD. HPV and cervical cancer: updates on an established relationship [J].Postgrad Med, 2008, 120(4):7-13.
9. Estojak J, Brent R, Golemis E A. Correlation of two-hybrid affinity data with in vitro measurements[J]. Mol Cell Biol, 1995, 15: 5820-5829.
10. Guarente L. Strategies for the identification of interacting proteins [J]. Proc Natl Acad Sci USA, 1993,90: 1639-1641.
11. Li Shuang, Liu Ping, Xi Lin, Jiang XueFeng, Zhou JianFeng, Wang ShiXuan, Meng Li, Lu YunPing, Ma Ding. Screening for novel binding proteins interacting with human papillomavirus type 18 E6 oncogene in the Hela cDNA library by yeast two hybrid system. J Huazhong Univ Sci Technolog Med Sci. 2008 Feb; 28(l):93-6.
12. Gilles C, Thompson E W. The epithelial to mesenchymal transition and nietastatic progression in carcinoma [J]. Breast J, 1996, 2:83-96.
13. Gilles C, Polette M, Zahm J et al. Vimentin contributes to human mammary epithelial cell migration [J]. J Cell Sci, 1999, 112(Pt 24):4615-4625.
14. Svitkina T M, Verkhovsky A B, Borisy G G. Plectin sidearms mediate interaction of intermediate filaments with with microtubules and other components of the cytoskeleton[J] J Cell Biol, 1996,135(4):991-1007.
15. Maniotis A, Chen C, Ingber D. Demonstration of mechanical connections between integrins,cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure[J].Proc Natl Acad, 1997,94:849-854.
16. Homan S, Mercurio A, LaFlamme S. Endothelial cells assemble two distinct alpha6beta4-containing vimentinassociated structures: roles for ligand binding and the beta4 cytoplasmic tail [J]. J Cell Sci, 1998, 111 (Pt 18): 2717-2728.
17. Goldman R D, Chou Y h, Prahlad V et al. Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems [J].Faseb J, 1999, 13 (Suppl 2):S261-S265.
18. Wu AL, Wang J, Zheleznyak A et al. Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane [J]. Mol Cell, 1999, 4(4):619-625
19. Gonzales M, Weksler B, Tsuruta D et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells [J]. Mol Biol Cell, 2001, 12(l):85-100.
20. Rock K L, Goldberg AL. Degradation of cell proteins and the generation of MhC class I-presented peptides [J]. Annu Rev Immunol, 1999, 17: 739-779.
21. Tureci O, Sahin U, Zwick C et al. Identification of a meiosis-specific protein as a member of the class of cancer/ testis antigens [J]. Proc Natl Acad Sci USA, 1998, 95: 5211-5216.
1 Lim Kp, Hamid S, Lau SH, Teo SH, Cheong SC: HPV infection anda the alterations of the pRB pathway in oral carcinogensis. Oncol Rep 17:1321-1326, 2007.
2 zur Hausen, H: Viruses in human cancers. Eur. J. Cancer 35:1878-1885, 1999.
3 zur Hausen, H: Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst 92:690-698, 2000.
4 Schwarz, E., U. K. Freese, L. Gissmann, W. Mayer, B. Roggenbuck, A. Stremlau, and H. zur Hausen: Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314: 111-114, 1985.
5 Scheffner, M., B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136, 1990.
6 Wazer, D. E., X. L. Liu, Q. Chu, Q. Gao, and V. Band: Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Proc. Natl. Acad. Sci.USA 92:3687-3691, 1995.
7 Werness, B. A., A. J. Levine, and P. M. Howley: Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248:76-79, 1990.
8 Hansen, R., and M. Oren: p53; from inductive signal to cellular effect. Curr. Opin. Genet. 7:46-51, 1997.
9 Levine, A. J: p53, the cellular gatekeeper for growth and division. Cell 88: 323-331, 1997.
10 Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE,Stoughton R and Shoemaker DD: Genome-wide survey of human alternative premRNA splicing with exon junction microarrays. Science 302: 2141-2144, 2003.
11 Strausberg RL, Feingold EA, Grouse LH, Derge JG Klausner RD, Collins FS, Wagner L,Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK,Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE,Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM,Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S,Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW,Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ and Marra MA: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA 99: 16899-16903, 2002.
12 Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H,Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S,Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T,Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H,Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K,Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y,Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K,Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K,Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y,Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S,Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H,Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K,Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A,Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T,Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T,Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T,Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y,Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y,Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S: Completesequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 36: 40-45,2004.
13 Mewes HW, Frishman D, Mayer KF et al. MIPS: analysis and annotation of proteins from whole genornes in 2005. Nucleic Acids Res 2006; 34(Database issue):D169-D172.
14 朱涛， 吴明富， 周金华， 等．卵巢癌肝转移灶高表达基因SFT2D1的生物信息学分析．生物磁学2005，5(4)：1-5．
15 杨美香，曲迅，韩克军，等．应用生物信息学方法分析人HCA56基因[J]．基础医学与临床，2005，25(2)：169—172．
16 Li Shuang, Liu Ping, Xi Lin, Jiang XueFeng, Zhou JianFeng, Wu MingFu, Wei Juncheng,Zhou Li, Wang Shixuan, Lu YunPing, Ma Ding. The expression of novel binding protein TMEM87B interacting with human papillomavirus type 18 E6 oncogene in Hela cDNA library by yeast two-hybrid system and its bioinformatic analysis. Oncol Rep. IF=1.7 2008 Aug; 20(2):421-7.
1. Bargonettij, ManfredI J J. Multiple roles of the tumor suppressor p53 [J]. Curr Opin Oncol, 2002, 14: 86-91.
2. Te Poele RH, et al. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. [J]. Cancer Res, 2002, 62(6): 1876-1883
3. Rebbaa A et al. Caspase inhibition switches doxorubicin-induced apoptosis to senescence. [J].Oncogene, 2003, 22(18): 2805-2811.
4. Blagosklonny MV. Prospective strategies to enforce selectively cell death in cancer cells. Oncogene, 2004, 23 (16): 2967-2975
5. Shay JW et al. Hallmarks of senescence in carcinogenesis and cancer therapy.Oncogene, 2004, 23 (16): 2919-2933.
6. Wang X et al. Induction of senescent-like growth arrest as a new target in anticancer treatment. Curr Cancer Drug Targets, 2003, 3 (2): 153-159.
7. Rachel S. R, Steven J K, Eric V, et al. Escape from Therapy-Induced Accelerated Cellular Senescence in p53-Null Lung Cancer Cells and in Human Lung Cancers. [J].Cancer Res, 2005, 65: (7):2795-2803.
8. Lynne WE, Xu Di, Catherine D, et al. Evasion of a Single-Step, Chemotherapy-Induced Senescence in Breast Cancer Cells: Implications for Treatment Response. [J]. Clin Cancer Res, 2005, 11(7):26378-2643.
9. Woodworth CD, Doneger J, Dipanolo JA, Immortalization of human foreskin keratinocytes various human papillomavirus DNA corresponds to their association with cervical carcinoma. [J].J Viol, 1989, 63 (1):159-164.
10. Gilles C, Thompson E W. The epithelial to mesenchymal transition and metastatic progression in carcinoma [J]. Breast J, 1996, 2:83-96.
11. Gilles C, Polette M, Zahm J et al. Vimentin contributes to human mammary epithelial cell migration [J]. J Cell Sci, 1999, 112(Pt 24):4615-4625.
12. Goldman R D, Chou Y h, Prahlad V et al. Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems [J].Faseb J, 1999, 13(Suppl2):S261-S265.
13. Gonzales M, Weksler B, Tsuruta D et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells [J]. Mol Biol Cell, 2001, 12(l):85-100.
14. Koji Nishio, Akira Inoue, Shanlou Qiao, Hiroshi Kondo, Akio Mimura Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol (2001) 116:321-327
15. GENRICH V. TOLSTONOG ROBERT L. SHOEMAN, ULRDCE TRAUB, and PETER TRAUB. Role of the Intermediate Filament Protein Vimentin in Delaying Senescence and in the Spontaneous Immortalization of Mouse Embryo Fibroblasts. DNA and cell biology. 20(9),2001:509-529.
16. Christy Hebner, Melanie Beglin, and Laimonis A. Laimins. Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation. J VIROL, Dec. 2007:12740-12747.
17. Bargonettij, Manfredl J J. Multiple roles of the tumor suppressor p53 [J]. Curr Opin Oncol, 2002, 14:86-91.
18. Changb D, Xuan Y, Broude E V , et al. Role of p53 and p21waflPcipl in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs [J]. Oncogene, 1999, 18 (34): 4808-4818.
1. Ruud LM Bekkers, et al. Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med ViroL 2004(14):95-.
2. Herrero R. Hildesheim A, Bratti C, et al. Population based stndy of human papillomavirus infection and cervical neoplasia in rural costa Rica. J Nat. Cancer Inst,2000, 92,464-474.
3. Infantolino C, Fabris P, Infantolino D, et al. Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases.Eur J Obstet Gynecol Reprod Biol, 2000, 93:71-75.
4. Cuzick J, Sasieni P, Davies P. et al. A systematic review of the role of human papillomavirus testing within a cervical screnning programme. Health Technol Assess.1999.3: 1-196.
5. Sellors JW, MahonyLB, Kaczorowski J, et al. Prevalence and predictors of human papillomavirus infection in women in Ontario,Canada. CMAJ. 2000, 163: 503-508.
6. Walboomer JMM, Jacohs MV, Bosch FX, et all Human papillomarvirus is a necessary cause of invasive cervical cancer worldwidel J Pathol, 1999, 189: 12-19.
7. Duttagupta C, Sengupta S. Roy M, et al. Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India. Eur J Cancer Prey, 2002, 11: 447-456.
8. Bosch FX. Munoz N. Chichareon S, et al. The causal relation between human papiliomavirus and cervical cancerl J Clin Pathol,2002,55:244-265.
9. Deacon JM, Evans CD, Yule R, et al. Sexual behaviour anti smoking as determinants of cervical HPV infection anti of CIN3 among those infected: a case control study nested within the Manchester cohort. Br J Cancer, 2000, 88: 1565-1572.
10. Lim a S V ,Mesqnita A M ,Cavalcante F G ,et al Sexually transmitted infections in a fem ale population in rural northeast Brazil: prevalence morbidity and risk factors[J].Trop Med Int Health, 2003, 8(7): 595.
11. Branca M ,G arbuglia A R ,Benedetto A .et al. Factors predicting the persistence of genital human papillomavirns infections and PAP smear abnormality in HIV 4 positive and HIV 5 negtive women during prospective follow up [J].Int J STD AIDS,2003,14:417.
12. Mathews WC. Screening for anal dysplasia associated with human papillomavirus. Top HIV Meal, 2003, 11(2):45-49.
13. Heard IP Tassie JMP Schmitz VP et al. Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load. Obstet Gynecol, 2000, 96(3): 403-409.
14. Bekkers RL, Massuger L F, Bulten J, et al. Epidemidogical and clinical aspects of hnman papillomavirus detection in the prevention of cervical cancer [J]. Rev Med virol, 2004, 14(2): 95-1051.
15. Mareel V Jacobs, et al. Distribution of 37 mucosotropic HPV types in women with cytologycally normal cervical smear: The age-related patterns for high-risk anti low risk Types. Int J Cancer, 2000,87: 221.
16. Stoler M H. Advances in cervical screening technology [J]. Mod Pathol, 2000, 13:275-284.
17. Lazcano-Ponce E, Herrero R. Munoz N, et al. Epidemiology of HPV infection among maxican women with normal cervical cytology. Int J Cancer, 2001, 91: 412-420.
18. Sellors JW, Karwalajtys TL, Kaczorowski JA, et at. Prevalence of infection with carcinogenic human papillomavirus among olderwomen [J]. CMAJ, 2002, 167:871-873.
19. Ponten J. Adami HO, Bergstrom R, et al. Strategies for global control of cervical cancer.Int J Cancer, 1995, 60: 1-26.
20. Ferrera A, Velema JP, Figueroa M, et al. Co-factors related to the causal relationship between human papillomavirus and invasive cervical cancer in Honduras. Int J Epidemiol, 2000. 29: 817-825.
21. Walboomer JMM, Jacobs MV, Bosch FX. et al. Hnman papillomarvirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12-19.
22. Franceschi S. Herrero R, Vecchia CL. Cervical cancer screening in Europe: what next?Eur J Cancel: 2000, 36: 2272-2275.
23. de Villiers E M .Relationship between steroid horm one contraceptives and HPV,cervical intraepithelial neoplasia and cervicai carcinoma [J]. IntCancer,2003,103(6):705-708.
24. Smith J S, Herrero R ,Bosetti C,et al.Herpes simplex virus 22 as a hum an papillomavirus cofactor in the etiology of invasive cervical cancer[J]. J Natl Cancer Inst,2002, 94(21):1604-613.
25. Munoz NP Bosch FXP de-Sanjose SP et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer, N Engl J MedP2003, 348(6):518-527.
26. Zur Hausen H. Papillomavirus causing cancer: Evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst, 2000,92: 690.
27．王照明，张建明．蒋清，等，尖锐湿疣中HPV感染的PCR技术检测与病毒形态观察[J]．中华病理学杂志．1993，22：162—164．
28．张溶清，李力，张玮1HPV感染与子宫颈癌发病关系的探讨[J]，广西医辩大学学报，2004．21(2)：222—224．
29. Shalinl I Kulasingam, et al. Evaluation of human papillomavirus testing in primary screening for cervical abnormalities caparison of sensitivity, sepecificity, and frecuency of referral. JAMA, 2002,288:1749.
30. Liaw KI, et aL Detection of human papillomavirus DNA in ctyologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst, 1999,94:954.
31. Eileen M Burd. Human papillomavirus and Cervical Cancer. Clin .Micro Rev 2003 ,16:1.
32. Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human pap illomavirus testing, and risk for cervical neop lasia: a 10-year cohort analysis[J]. J Natl Cancer Inst,2003, 95: 46-52.
33. Nobbenhuis MA, Walboomers JM, Helmerhorst TJ, et al, Relation of human pap illomavirus status to cervical lesion and consequences for cervical cancer screening: a p rospective study [J]. Lancet, 1999, 354: 20-25.
34. Kiatpongsan S, Niruthisard S, Mutirangura A, et al. Role of human pap illomavirusDNA testing inmanagement ofwomen with a typical squamous cells of undetermined significance [J]. Int J Gynecol Cancer, 2006, 16 (1): 262-265.
35. Angel Chao, et al. Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. AmJ Obstet Gyyneco, 2004, 190:1046.
36. Nobbenhuis MAE, et al. Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer, 2001. 84:796.
37. Andersson S, Safari H, MintsM. Type distribution, viral load and integration status of high risk human pap illomavirus in p re-stages of cervical cancer [J]. Br J Cancer, 2005, 92(12): 2195-2200.
38. Margaret E C. The role of human papillomavirus in risk management [J]. Gynecol Prac,2003.3 (3):229-233.
39. Kuhn L Denny L, Pollack A. et al. Hnman papillomarvirus DNA Testing for cervical cancer screening in low resource settings. J Natl Cancer Inst, 2000, 92: 818-825.
40. Peh WLP Middleton KP Christensen NPet al. Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol. 2002.76(20): 10401-10416.
41. ARC working group on the evaluation of carcinogenic risks to humans. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomavirus [M]. Lyon, France: WHO, 1995, 64.
42. WU Y, CHEN Y, LI L, et al. Associations of high2risk HPV types and viral load wit h cervical cancer in China [J]. J Clin Virol, 2006, 35(3):264-269.
43. TRIMBL E C L, PIANTADOSI S, GRAVITT P, et al. Spontaneous regression of high grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype [J].Clin Cancer Res, 2005, 11 (3): 4717-4723.
44. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in youngwomen: a longitudinal cohort study. Lancet, 2001, 357:1831-1836.
45. Clifford GM, Smith JS, Aguado T et al. Comparison of HPV type distribution in high grade cervical lesions and cervical cancer: ameta2abalysis[J]. Br J Cancer, 2003, 89:101-105.
46．杨英捷，赵健，李雪倩．人乳头状瘤病毒不同亚型感染与宫颈病变的相关性．中国妇产科临床杂志，2006．7(4)：253-256．
47．汤惠茹，魏丽惠，吴瑞芳等，不同程度宫颈病变感染人乳头瘤病毒的优势亚型，华中科技大学学报(医学版)．2006，35(6)：771-773．
48. Tsai H J, Wu CH, Lai HL, et al. Association between quantitative high2risk human papillomavirus DNA load and cervical intraepithelial neoplasm risk [J]. Cancer Epidemiol Biomarkers Prey, 2005, 14: 2544-2549.
49. Maaike C Schellekens, et al. Prevalance of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia. Gyneco Oncol, 2004, 93: 49.
50. Deluca GD, Lucero RH, Martin-de-Civetta MTP, et al. Human papillomavirus genotypes in women with cervical cytological abnormalities from an area with high incidence of cervical cancer: Rev-Inst Med Trop Sao Paulo, 2004, 46(1):9-12.
51．徐成康，梅卓贤．宫颈人乳头状瘤病毒感染的筛查及其意义[J]．中山医科大学学报，1998，19：2231．
52. Bulk S, Berkhof J, Bolkmans NW. et al. Preferential risk of HPV 16 for sqnamous cell carcinoma and of HPV 18 for adenocarcinoma of the cervix compared to women with normal cytology in the Netherlans [J]. Br J Cancer, 2006, 94 (1): 171-175.
53. A ltekruse SF, Lacey JV,Brinton LA, et al. Comparison of human papillom avirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States[J].Am J Obstet Gynecol.2003,188(3):657-663.
54. Lombard I, Vincent Salomon A, Validire P, et al. Human papillomavirus genetype as a major determinant of the course of cervical cancer. J Clin Oncol, 1998, 16: 2613-2619.
55. Nubia Munoz, et al. Epidemiotogic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003, 348:518.
56. Tarkowski TA, Koumans EH, SawyerM, et al. Ep idemiology of human pap illomavirus infection and abnormal cytologic test results inan urban adolescent population [J]. J InfectDis, 2004, 189:46-50.
57. Sang Ah Lee, et al. Multiple HPV infection in cervical cancer screened by HPV DNA Chip. Cancer Letters, 2003, 198:187.
58. Womack SD, Chirenje ZM, Gsffikin L, et al1 HPV2based cervical cancer screening in a population at high risk for HIV infectionl Int J Cancer, 2000 ;85:206-210.
59. Georgette Damasus-Awatai, et al. Human papilloma virus and cervical screening. Curr Opin Obstet Gynecol, 2003, 15: 473.
60. Ho GY, Bierman R, BeardsleyL, et al. Natural history of cervical vaginal papillomavirus infection in young women [J]. N Engl J Med, 1998. 338:423-428.
61. Dalstein V, Riet hmuller D, Pretet J L, et al. Persistence and load of high risk HPV are predictors for development of high grade cervical lesions: a longitudinal French cohort study [J]. Int J Cancer, 2003, 106 (3): 396-403.
62. Schlecht NF, Kulaga S, Robitaille J, et al. Persistent Human Pap illomavirus infection a p redictor of Cervical Intraep ithelial Neop lasia [J]. JAMA, 2001, 286:3106-3114.
63. Bory JP. Cucherousset J , Lorenzato M, et al. Recurrent human pap illomavirus infection detected with the hybrid cap ture Ⅱ assay selectswomen with normal cervical smear at risk for developing high grade cervical lesions: a longitudinal study of 3, 091 women [J]. Int J cancer, 2002, 102:519-525.
64. Nicolas F Schlecht, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA, 2001, 286:3106.
65. Josefsson AM, Magnusson PKE, Ylitalo N, et al. Viral load of human papilloma virus 16 as a determinant for delelopment of cervical carcinoma in situ :a nested case-control studyl Lancet ,2000,355:2189-2193.
66. Agnethea.MJ, Patrik KM, Nathalie Y et al1 Viral load of huaman virus16 asadetermianant for development of cervical carcinoma insitu: anewt case control study.J The Lancet, 2001, 6 (355): 2189.
67. Glaria YF Ho, et al. Persistent genital human papillomavirus infection as a risk Factor for persistent cervical dysplasia. J Natl Cancer Inst, 1995, 87: 1365.
68．黄志宏，钱德英，王丁等．人乳头状瘤病毒负荷量与官颈癌及官颈癌前病变的相关研究，中国妇幼保健，2006，21(11)：1557-1559．
69. Sun CA, et al. Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions. Int J Gyne Obstet, 2002, 76: 41.
70. Sun Chien An, et al. The significance of human papollomavirus viral load in prediction of histologic servity and size of squamous intraepithelial lesion of uterine cervix. Gyneco Onto, 2001, 83: 95.
71. Nicolas FS, Andrea T, Eliane DF et all Viral load as a p redictor of the risk of cervical intraepithelial neoplasial Int J Cancer, 2003, 103: 519.
72. Dalstein V, Riet hmuller D, Pretet J L, et al. Persistence and load of high risk HPV are predictors for development of high grade cervical lesions: a longitudinal French cohort study [J]1 Int J Cancer, 2003, 106 (3) :396-403.
73. Schlecht N F, Trevisan A, Franco E D, et al. Viral load as a predictor of the risk of cervical intraepithelial neoplasia[J]1 Int J Cancer, 2003, 103:519-524.
74. David C Swan et al. Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Micro, 1999,37:1030.
75. Agnetha M Josefsson, et al. Viral load of human papillomavirus 16 as a determinant for development of cervical carcinoma in situ: A nested case-control. Lancet, 2000,355:2189.
76. Nathalie Ylitalo, et al. Consistent high vival load of human papillomavirus 16 and risk of cervical carcinoma in situ: A nested case-control study. Lancet, 2000, 355:2194.
77. Moberg M, Gustavsson I, Wilander E, et al1 High viral loads of human papillomavirus predict risk of invasive cervical carcinoma [J] 1 Br J Cancer. 2005, 92 (5):891-894.
78. Lorincz AT, Castle PE, Sherman ME, et al. Viral load of human papillomavirus anti risk of CIN3 or cervical cancer [J]. Lancet, 2002, 360 (9328): 228-229.
79. Attila T Lorincz, et al. Viral load of human papillomavirus and risk of CIN-3 or cervical cancer. Lancet, 2002, 360: 228.
80. Sherman M E, Schiffman M , Cox J T, et al. Effect s of age and human papillomaviral load oncolposcopy triage : data from the randomized Atypical Squamoas Cells of Undetermined Significance/Low-Grade Squamous Int raepitheiial Lesion Triage Study(ALTS) [J]. J Natl Cancer. 2002, 94:102-107.
2. Nirchio V, Lipsi R, Fusilli S, et al. HPV infection: comparison between morphological studies and molecular biology [J].Pathologica, 2008, 100 (3): 149-155.
3. Ding B, Chi SG, Kim Sh, et al. Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following h2O2 exposure[J].J Cell Sci, 2007; 1; 120(13):2284-2294.
4. Scheffher, M., B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136, 1990.
5. Nomine Y, Masson M, Charbonnier S, et al.Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis [J]. Mol Cell, 2006, 21(5): 665-678.
6. Zur Hausen, H: Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst 92:690-698, 2000.
7. Zur Hausen, H: Viruses in human cancers. Eur. J. Cancer 35:1878-1885, 1999.
8. Subramanya D, Grivas PD. HPV and cervical cancer: updates on an established relationship [J].Postgrad Med, 2008, 120(4):7-13.
9. Estojak J, Brent R, Golemis E A. Correlation of two-hybrid affinity data with in vitro measurements[J]. Mol Cell Biol, 1995, 15: 5820-5829.
10. Guarente L. Strategies for the identification of interacting proteins [J]. Proc Natl Acad Sci USA, 1993,90: 1639-1641.
11. Li Shuang, Liu Ping, Xi Lin, Jiang XueFeng, Zhou JianFeng, Wang ShiXuan, Meng Li, Lu YunPing, Ma Ding. Screening for novel binding proteins interacting with human papillomavirus type 18 E6 oncogene in the Hela cDNA library by yeast two hybrid system. J Huazhong Univ Sci Technolog Med Sci. 2008 Feb; 28(l):93-6.
12. Gilles C, Thompson E W. The epithelial to mesenchymal transition and nietastatic progression in carcinoma [J]. Breast J, 1996, 2:83-96.
13. Gilles C, Polette M, Zahm J et al. Vimentin contributes to human mammary epithelial cell migration [J]. J Cell Sci, 1999, 112(Pt 24):4615-4625.
14. Svitkina T M, Verkhovsky A B, Borisy G G. Plectin sidearms mediate interaction of intermediate filaments with with microtubules and other components of the cytoskeleton[J] J Cell Biol, 1996,135(4):991-1007.
15. Maniotis A, Chen C, Ingber D. Demonstration of mechanical connections between integrins,cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure[J].Proc Natl Acad, 1997,94:849-854.
16. Homan S, Mercurio A, LaFlamme S. Endothelial cells assemble two distinct alpha6beta4-containing vimentinassociated structures: roles for ligand binding and the beta4 cytoplasmic tail [J]. J Cell Sci, 1998, 111 (Pt 18): 2717-2728.
17. Goldman R D, Chou Y h, Prahlad V et al. Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems [J].Faseb J, 1999, 13 (Suppl 2):S261-S265.
18. Wu AL, Wang J, Zheleznyak A et al. Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane [J]. Mol Cell, 1999, 4(4):619-625
19. Gonzales M, Weksler B, Tsuruta D et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells [J]. Mol Biol Cell, 2001, 12(l):85-100.
20. Rock K L, Goldberg AL. Degradation of cell proteins and the generation of MhC class I-presented peptides [J]. Annu Rev Immunol, 1999, 17: 739-779.
21. Tureci O, Sahin U, Zwick C et al. Identification of a meiosis-specific protein as a member of the class of cancer/ testis antigens [J]. Proc Natl Acad Sci USA, 1998, 95: 5211-5216.
1 Lim Kp, Hamid S, Lau SH, Teo SH, Cheong SC: HPV infection anda the alterations of the pRB pathway in oral carcinogensis. Oncol Rep 17:1321-1326, 2007.
2 zur Hausen, H: Viruses in human cancers. Eur. J. Cancer 35:1878-1885, 1999.
3 zur Hausen, H: Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst 92:690-698, 2000.
4 Schwarz, E., U. K. Freese, L. Gissmann, W. Mayer, B. Roggenbuck, A. Stremlau, and H. zur Hausen: Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314: 111-114, 1985.
5 Scheffner, M., B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136, 1990.
6 Wazer, D. E., X. L. Liu, Q. Chu, Q. Gao, and V. Band: Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Proc. Natl. Acad. Sci.USA 92:3687-3691, 1995.
7 Werness, B. A., A. J. Levine, and P. M. Howley: Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248:76-79, 1990.
8 Hansen, R., and M. Oren: p53; from inductive signal to cellular effect. Curr. Opin. Genet. 7:46-51, 1997.
9 Levine, A. J: p53, the cellular gatekeeper for growth and division. Cell 88: 323-331, 1997.
10 Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE,Stoughton R and Shoemaker DD: Genome-wide survey of human alternative premRNA splicing with exon junction microarrays. Science 302: 2141-2144, 2003.
11 Strausberg RL, Feingold EA, Grouse LH, Derge JG Klausner RD, Collins FS, Wagner L,Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK,Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE,Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM,Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S,Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW,Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ and Marra MA: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA 99: 16899-16903, 2002.
12 Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H,Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S,Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T,Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H,Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K,Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y,Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K,Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K,Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y,Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S,Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H,Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K,Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A,Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T,Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T,Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T,Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y,Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y,Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S: Completesequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 36: 40-45,2004.
13 Mewes HW, Frishman D, Mayer KF et al. MIPS: analysis and annotation of proteins from whole genornes in 2005. Nucleic Acids Res 2006; 34(Database issue):D169-D172.
14 朱涛， 吴明富， 周金华， 等．卵巢癌肝转移灶高表达基因SFT2D1的生物信息学分析．生物磁学2005，5(4)：1-5．
15 杨美香，曲迅，韩克军，等．应用生物信息学方法分析人HCA56基因[J]．基础医学与临床，2005，25(2)：169—172．
16 Li Shuang, Liu Ping, Xi Lin, Jiang XueFeng, Zhou JianFeng, Wu MingFu, Wei Juncheng,Zhou Li, Wang Shixuan, Lu YunPing, Ma Ding. The expression of novel binding protein TMEM87B interacting with human papillomavirus type 18 E6 oncogene in Hela cDNA library by yeast two-hybrid system and its bioinformatic analysis. Oncol Rep. IF=1.7 2008 Aug; 20(2):421-7.
1. Bargonettij, ManfredI J J. Multiple roles of the tumor suppressor p53 [J]. Curr Opin Oncol, 2002, 14: 86-91.
2. Te Poele RH, et al. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. [J]. Cancer Res, 2002, 62(6): 1876-1883
3. Rebbaa A et al. Caspase inhibition switches doxorubicin-induced apoptosis to senescence. [J].Oncogene, 2003, 22(18): 2805-2811.
4. Blagosklonny MV. Prospective strategies to enforce selectively cell death in cancer cells. Oncogene, 2004, 23 (16): 2967-2975
5. Shay JW et al. Hallmarks of senescence in carcinogenesis and cancer therapy.Oncogene, 2004, 23 (16): 2919-2933.
6. Wang X et al. Induction of senescent-like growth arrest as a new target in anticancer treatment. Curr Cancer Drug Targets, 2003, 3 (2): 153-159.
7. Rachel S. R, Steven J K, Eric V, et al. Escape from Therapy-Induced Accelerated Cellular Senescence in p53-Null Lung Cancer Cells and in Human Lung Cancers. [J].Cancer Res, 2005, 65: (7):2795-2803.
8. Lynne WE, Xu Di, Catherine D, et al. Evasion of a Single-Step, Chemotherapy-Induced Senescence in Breast Cancer Cells: Implications for Treatment Response. [J]. Clin Cancer Res, 2005, 11(7):26378-2643.
9. Woodworth CD, Doneger J, Dipanolo JA, Immortalization of human foreskin keratinocytes various human papillomavirus DNA corresponds to their association with cervical carcinoma. [J].J Viol, 1989, 63 (1):159-164.
10. Gilles C, Thompson E W. The epithelial to mesenchymal transition and metastatic progression in carcinoma [J]. Breast J, 1996, 2:83-96.
11. Gilles C, Polette M, Zahm J et al. Vimentin contributes to human mammary epithelial cell migration [J]. J Cell Sci, 1999, 112(Pt 24):4615-4625.
12. Goldman R D, Chou Y h, Prahlad V et al. Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems [J].Faseb J, 1999, 13(Suppl2):S261-S265.
13. Gonzales M, Weksler B, Tsuruta D et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells [J]. Mol Biol Cell, 2001, 12(l):85-100.
14. Koji Nishio, Akira Inoue, Shanlou Qiao, Hiroshi Kondo, Akio Mimura Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol (2001) 116:321-327
15. GENRICH V. TOLSTONOG ROBERT L. SHOEMAN, ULRDCE TRAUB, and PETER TRAUB. Role of the Intermediate Filament Protein Vimentin in Delaying Senescence and in the Spontaneous Immortalization of Mouse Embryo Fibroblasts. DNA and cell biology. 20(9),2001:509-529.
16. Christy Hebner, Melanie Beglin, and Laimonis A. Laimins. Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation. J VIROL, Dec. 2007:12740-12747.
17. Bargonettij, Manfredl J J. Multiple roles of the tumor suppressor p53 [J]. Curr Opin Oncol, 2002, 14:86-91.
18. Changb D, Xuan Y, Broude E V , et al. Role of p53 and p21waflPcipl in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs [J]. Oncogene, 1999, 18 (34): 4808-4818.
1. Ruud LM Bekkers, et al. Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med ViroL 2004(14):95-.
2. Herrero R. Hildesheim A, Bratti C, et al. Population based stndy of human papillomavirus infection and cervical neoplasia in rural costa Rica. J Nat. Cancer Inst,2000, 92,464-474.
3. Infantolino C, Fabris P, Infantolino D, et al. Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases.Eur J Obstet Gynecol Reprod Biol, 2000, 93:71-75.
4. Cuzick J, Sasieni P, Davies P. et al. A systematic review of the role of human papillomavirus testing within a cervical screnning programme. Health Technol Assess.1999.3: 1-196.
5. Sellors JW, MahonyLB, Kaczorowski J, et al. Prevalence and predictors of human papillomavirus infection in women in Ontario,Canada. CMAJ. 2000, 163: 503-508.
6. Walboomer JMM, Jacohs MV, Bosch FX, et all Human papillomarvirus is a necessary cause of invasive cervical cancer worldwidel J Pathol, 1999, 189: 12-19.
7. Duttagupta C, Sengupta S. Roy M, et al. Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India. Eur J Cancer Prey, 2002, 11: 447-456.
8. Bosch FX. Munoz N. Chichareon S, et al. The causal relation between human papiliomavirus and cervical cancerl J Clin Pathol,2002,55:244-265.
9. Deacon JM, Evans CD, Yule R, et al. Sexual behaviour anti smoking as determinants of cervical HPV infection anti of CIN3 among those infected: a case control study nested within the Manchester cohort. Br J Cancer, 2000, 88: 1565-1572.
10. Lim a S V ,Mesqnita A M ,Cavalcante F G ,et al Sexually transmitted infections in a fem ale population in rural northeast Brazil: prevalence morbidity and risk factors[J].Trop Med Int Health, 2003, 8(7): 595.
11. Branca M ,G arbuglia A R ,Benedetto A .et al. Factors predicting the persistence of genital human papillomavirns infections and PAP smear abnormality in HIV 4 positive and HIV 5 negtive women during prospective follow up [J].Int J STD AIDS,2003,14:417.
12. Mathews WC. Screening for anal dysplasia associated with human papillomavirus. Top HIV Meal, 2003, 11(2):45-49.
13. Heard IP Tassie JMP Schmitz VP et al. Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load. Obstet Gynecol, 2000, 96(3): 403-409.
14. Bekkers RL, Massuger L F, Bulten J, et al. Epidemidogical and clinical aspects of hnman papillomavirus detection in the prevention of cervical cancer [J]. Rev Med virol, 2004, 14(2): 95-1051.
15. Mareel V Jacobs, et al. Distribution of 37 mucosotropic HPV types in women with cytologycally normal cervical smear: The age-related patterns for high-risk anti low risk Types. Int J Cancer, 2000,87: 221.
16. Stoler M H. Advances in cervical screening technology [J]. Mod Pathol, 2000, 13:275-284.
17. Lazcano-Ponce E, Herrero R. Munoz N, et al. Epidemiology of HPV infection among maxican women with normal cervical cytology. Int J Cancer, 2001, 91: 412-420.
18. Sellors JW, Karwalajtys TL, Kaczorowski JA, et at. Prevalence of infection with carcinogenic human papillomavirus among olderwomen [J]. CMAJ, 2002, 167:871-873.
19. Ponten J. Adami HO, Bergstrom R, et al. Strategies for global control of cervical cancer.Int J Cancer, 1995, 60: 1-26.
20. Ferrera A, Velema JP, Figueroa M, et al. Co-factors related to the causal relationship between human papillomavirus and invasive cervical cancer in Honduras. Int J Epidemiol, 2000. 29: 817-825.
21. Walboomer JMM, Jacobs MV, Bosch FX. et al. Hnman papillomarvirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12-19.
22. Franceschi S. Herrero R, Vecchia CL. Cervical cancer screening in Europe: what next?Eur J Cancel: 2000, 36: 2272-2275.
23. de Villiers E M .Relationship between steroid horm one contraceptives and HPV,cervical intraepithelial neoplasia and cervicai carcinoma [J]. IntCancer,2003,103(6):705-708.
24. Smith J S, Herrero R ,Bosetti C,et al.Herpes simplex virus 22 as a hum an papillomavirus cofactor in the etiology of invasive cervical cancer[J]. J Natl Cancer Inst,2002, 94(21):1604-613.
25. Munoz NP Bosch FXP de-Sanjose SP et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer, N Engl J MedP2003, 348(6):518-527.
26. Zur Hausen H. Papillomavirus causing cancer: Evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst, 2000,92: 690.
27．王照明，张建明．蒋清，等，尖锐湿疣中HPV感染的PCR技术检测与病毒形态观察[J]．中华病理学杂志．1993，22：162—164．
28．张溶清，李力，张玮1HPV感染与子宫颈癌发病关系的探讨[J]，广西医辩大学学报，2004．21(2)：222—224．
29. Shalinl I Kulasingam, et al. Evaluation of human papillomavirus testing in primary screening for cervical abnormalities caparison of sensitivity, sepecificity, and frecuency of referral. JAMA, 2002,288:1749.
30. Liaw KI, et aL Detection of human papillomavirus DNA in ctyologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst, 1999,94:954.
31. Eileen M Burd. Human papillomavirus and Cervical Cancer. Clin .Micro Rev 2003 ,16:1.
32. Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human pap illomavirus testing, and risk for cervical neop lasia: a 10-year cohort analysis[J]. J Natl Cancer Inst,2003, 95: 46-52.
33. Nobbenhuis MA, Walboomers JM, Helmerhorst TJ, et al, Relation of human pap illomavirus status to cervical lesion and consequences for cervical cancer screening: a p rospective study [J]. Lancet, 1999, 354: 20-25.
34. Kiatpongsan S, Niruthisard S, Mutirangura A, et al. Role of human pap illomavirusDNA testing inmanagement ofwomen with a typical squamous cells of undetermined significance [J]. Int J Gynecol Cancer, 2006, 16 (1): 262-265.
35. Angel Chao, et al. Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. AmJ Obstet Gyyneco, 2004, 190:1046.
36. Nobbenhuis MAE, et al. Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer, 2001. 84:796.
37. Andersson S, Safari H, MintsM. Type distribution, viral load and integration status of high risk human pap illomavirus in p re-stages of cervical cancer [J]. Br J Cancer, 2005, 92(12): 2195-2200.
38. Margaret E C. The role of human papillomavirus in risk management [J]. Gynecol Prac,2003.3 (3):229-233.
39. Kuhn L Denny L, Pollack A. et al. Hnman papillomarvirus DNA Testing for cervical cancer screening in low resource settings. J Natl Cancer Inst, 2000, 92: 818-825.
40. Peh WLP Middleton KP Christensen NPet al. Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol. 2002.76(20): 10401-10416.
41. ARC working group on the evaluation of carcinogenic risks to humans. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomavirus [M]. Lyon, France: WHO, 1995, 64.
42. WU Y, CHEN Y, LI L, et al. Associations of high2risk HPV types and viral load wit h cervical cancer in China [J]. J Clin Virol, 2006, 35(3):264-269.
43. TRIMBL E C L, PIANTADOSI S, GRAVITT P, et al. Spontaneous regression of high grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype [J].Clin Cancer Res, 2005, 11 (3): 4717-4723.
44. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in youngwomen: a longitudinal cohort study. Lancet, 2001, 357:1831-1836.
45. Clifford GM, Smith JS, Aguado T et al. Comparison of HPV type distribution in high grade cervical lesions and cervical cancer: ameta2abalysis[J]. Br J Cancer, 2003, 89:101-105.
46．杨英捷，赵健，李雪倩．人乳头状瘤病毒不同亚型感染与宫颈病变的相关性．中国妇产科临床杂志，2006．7(4)：253-256．
47．汤惠茹，魏丽惠，吴瑞芳等，不同程度宫颈病变感染人乳头瘤病毒的优势亚型，华中科技大学学报(医学版)．2006，35(6)：771-773．
48. Tsai H J, Wu CH, Lai HL, et al. Association between quantitative high2risk human papillomavirus DNA load and cervical intraepithelial neoplasm risk [J]. Cancer Epidemiol Biomarkers Prey, 2005, 14: 2544-2549.
49. Maaike C Schellekens, et al. Prevalance of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia. Gyneco Oncol, 2004, 93: 49.
50. Deluca GD, Lucero RH, Martin-de-Civetta MTP, et al. Human papillomavirus genotypes in women with cervical cytological abnormalities from an area with high incidence of cervical cancer: Rev-Inst Med Trop Sao Paulo, 2004, 46(1):9-12.
51．徐成康，梅卓贤．宫颈人乳头状瘤病毒感染的筛查及其意义[J]．中山医科大学学报，1998，19：2231．
52. Bulk S, Berkhof J, Bolkmans NW. et al. Preferential risk of HPV 16 for sqnamous cell carcinoma and of HPV 18 for adenocarcinoma of the cervix compared to women with normal cytology in the Netherlans [J]. Br J Cancer, 2006, 94 (1): 171-175.
53. A ltekruse SF, Lacey JV,Brinton LA, et al. Comparison of human papillom avirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States[J].Am J Obstet Gynecol.2003,188(3):657-663.
54. Lombard I, Vincent Salomon A, Validire P, et al. Human papillomavirus genetype as a major determinant of the course of cervical cancer. J Clin Oncol, 1998, 16: 2613-2619.
55. Nubia Munoz, et al. Epidemiotogic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003, 348:518.
56. Tarkowski TA, Koumans EH, SawyerM, et al. Ep idemiology of human pap illomavirus infection and abnormal cytologic test results inan urban adolescent population [J]. J InfectDis, 2004, 189:46-50.
57. Sang Ah Lee, et al. Multiple HPV infection in cervical cancer screened by HPV DNA Chip. Cancer Letters, 2003, 198:187.
58. Womack SD, Chirenje ZM, Gsffikin L, et al1 HPV2based cervical cancer screening in a population at high risk for HIV infectionl Int J Cancer, 2000 ;85:206-210.
59. Georgette Damasus-Awatai, et al. Human papilloma virus and cervical screening. Curr Opin Obstet Gynecol, 2003, 15: 473.
60. Ho GY, Bierman R, BeardsleyL, et al. Natural history of cervical vaginal papillomavirus infection in young women [J]. N Engl J Med, 1998. 338:423-428.
61. Dalstein V, Riet hmuller D, Pretet J L, et al. Persistence and load of high risk HPV are predictors for development of high grade cervical lesions: a longitudinal French cohort study [J]. Int J Cancer, 2003, 106 (3): 396-403.
62. Schlecht NF, Kulaga S, Robitaille J, et al. Persistent Human Pap illomavirus infection a p redictor of Cervical Intraep ithelial Neop lasia [J]. JAMA, 2001, 286:3106-3114.
63. Bory JP. Cucherousset J , Lorenzato M, et al. Recurrent human pap illomavirus infection detected with the hybrid cap ture Ⅱ assay selectswomen with normal cervical smear at risk for developing high grade cervical lesions: a longitudinal study of 3, 091 women [J]. Int J cancer, 2002, 102:519-525.
64. Nicolas F Schlecht, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA, 2001, 286:3106.
65. Josefsson AM, Magnusson PKE, Ylitalo N, et al. Viral load of human papilloma virus 16 as a determinant for delelopment of cervical carcinoma in situ :a nested case-control studyl Lancet ,2000,355:2189-2193.
66. Agnethea.MJ, Patrik KM, Nathalie Y et al1 Viral load of huaman virus16 asadetermianant for development of cervical carcinoma insitu: anewt case control study.J The Lancet, 2001, 6 (355): 2189.
67. Glaria YF Ho, et al. Persistent genital human papillomavirus infection as a risk Factor for persistent cervical dysplasia. J Natl Cancer Inst, 1995, 87: 1365.
68．黄志宏，钱德英，王丁等．人乳头状瘤病毒负荷量与官颈癌及官颈癌前病变的相关研究，中国妇幼保健，2006，21(11)：1557-1559．
69. Sun CA, et al. Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions. Int J Gyne Obstet, 2002, 76: 41.
70. Sun Chien An, et al. The significance of human papollomavirus viral load in prediction of histologic servity and size of squamous intraepithelial lesion of uterine cervix. Gyneco Onto, 2001, 83: 95.
71. Nicolas FS, Andrea T, Eliane DF et all Viral load as a p redictor of the risk of cervical intraepithelial neoplasial Int J Cancer, 2003, 103: 519.
72. Dalstein V, Riet hmuller D, Pretet J L, et al. Persistence and load of high risk HPV are predictors for development of high grade cervical lesions: a longitudinal French cohort study [J]1 Int J Cancer, 2003, 106 (3) :396-403.
73. Schlecht N F, Trevisan A, Franco E D, et al. Viral load as a predictor of the risk of cervical intraepithelial neoplasia[J]1 Int J Cancer, 2003, 103:519-524.
74. David C Swan et al. Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Micro, 1999,37:1030.
75. Agnetha M Josefsson, et al. Viral load of human papillomavirus 16 as a determinant for development of cervical carcinoma in situ: A nested case-control. Lancet, 2000,355:2189.
76. Nathalie Ylitalo, et al. Consistent high vival load of human papillomavirus 16 and risk of cervical carcinoma in situ: A nested case-control study. Lancet, 2000, 355:2194.
77. Moberg M, Gustavsson I, Wilander E, et al1 High viral loads of human papillomavirus predict risk of invasive cervical carcinoma [J] 1 Br J Cancer. 2005, 92 (5):891-894.
78. Lorincz AT, Castle PE, Sherman ME, et al. Viral load of human papillomavirus anti risk of CIN3 or cervical cancer [J]. Lancet, 2002, 360 (9328): 228-229.
79. Attila T Lorincz, et al. Viral load of human papillomavirus and risk of CIN-3 or cervical cancer. Lancet, 2002, 360: 228.
80. Sherman M E, Schiffman M , Cox J T, et al. Effect s of age and human papillomaviral load oncolposcopy triage : data from the randomized Atypical Squamoas Cells of Undetermined Significance/Low-Grade Squamous Int raepitheiial Lesion Triage Study(ALTS) [J]. J Natl Cancer. 2002, 94:102-107.
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