维吾尔族及汉族妇女高危型HPV检测、L1蛋白表达与病毒整合的比较性研究
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摘要
目的：探讨人高危型乳头瘤病毒(HPV)在维吾尔族宫颈炎,宫颈癌前病变,宫颈癌中的分布及意义。检测人乳头状瘤病毒(HPV) L1壳蛋白在维、汉族HPV阳性、宫颈不同病变脱落细胞中的表达和意义。检测新疆维汉妇女宫颈鳞癌及癌前病变组织中HPV16存在状态，分析在维族宫颈癌发生发展中的作用，以汉族妇女为对照分析其民族差异，探索维吾尔族HPV低感染率，宫颈癌高发的原因，探索HPV分型、HPVL1蛋白及E2/E6比值在新疆维吾尔族妇女中是否能作为宫颈病变严重程度的预测因子。方法：应用Hybrimax基因芯片导流杂交技术，对2011年11月～2012年10月在新疆自治区人民医院病房及门诊就诊的HC2结果阳性的428位女性的宫颈细胞标本进行HPV基因型分型检测，对其中301例液基细胞学涂片用免疫细胞化学法检测HPV L1壳蛋白在宫颈脱落细胞中的表达。对维汉宫颈病变患者细胞学DNA采用多重实时PCR检测HPV-16E2和E6拷贝数，通过E2/E6比值指示各样本HPV16存在状态。结果：HPV16型在维吾尔族及汉族妇女在慢性宫颈炎，宫颈癌前病变和宫颈癌三者比较中,差异具有统计学意义(P<0.05)，两民族间的分布无统计学差异。HPV感染在两个民族同样是以单一感染为主，其中HPV16型单一感染最多。HPV16感染类型在各年龄段的分布无明显差异；本组资料维吾尔族妇女中除HPV16、18型外，维吾尔族妇女全部宫颈脱落细胞中（宫颈炎，癌前病变及宫颈癌）常见亚型检出次数依次为HPV52、53、58、39、68，31、66、56、6和11型。汉族妇女为HPV52、58、53、31、33、68、66、39、45、11、6和CP8304型。维吾尔族妇女中L1的表达阳性率为：慢性宫颈炎31%（20/64）,CIN162.5%(15/24)，CIN2/327%(7/26)，宫颈癌无表达。比较差异均有统计学意义(P＜0.05),随病变程度的加重, HPV L1壳蛋白阳性表达率呈下降的趋势。汉族妇检测液基涂片中的L1蛋白表达率为，慢性宫为39%（32/83），CIN159%(23/39)，CIN2/326%(10/39)，宫颈癌无表达，比较差异均有统计学意义(P＜0.05)。维吾尔族妇女与汉族妇女之间比较无统计学差异(均P＞0.05)。HPV16整合比率（整合型+混合型）构成比随着宫颈病变级别的升高，呈上升趋势，但是差异无统计学意义（P＞0.05）；整合比率（混合型+游离型）在维吾尔族及汉族之间比较差异无统计学意义（P＞0.05）；两个民族不同程度的宫颈病变中，HPV16的E2/E6比值均数比较差异无统计学意义。结论： HPV感染是宫颈癌前病变和宫颈癌的主要致病因素；HPV16型感染是在正常宫颈、癌前病变及宫颈癌中常见的型别，但是随着病变进展占比例增加，宫颈各病变中HPV感染以单一感染为主；HPV L1壳蛋白在CIN和SCC中的阳性表达率随着病变程度加重呈下降趋势，HPV L1壳蛋白在两民族同级别宫颈病变之间的表达率无差异；HPV16-DNAE2整合比率与宫经病变在两民族之间比较未见有区别。维吾尔族HPV感染率低，而宫颈癌高发可能存在其它因素。HPV16型分型、HPVL1蛋白检测及HPV整合状态有望成为预测维吾尔族宫颈病变严重程度的重要生物学标志物。
Objective: To investigate the distribution and significance of the HPV16in chroniccervicitis, Cervical intraepithelial neoplasia (CIN) and cervical carcinoma. To evaluate theexpression and clinical significance of human papilloma virus (HPV) L1capsid protein incytologic specimens of the cervix from HPV-positive Uighur and Han women. Todetect physical status of human papillomavirus(HPV)16in cervical lesions tissue inUighur women in Xinjiang so as to explore the relation with Severity of cervical lesionsXinjiang Uighur women and Han women in China. Methods: In Part Ⅰ，428patientswith Hr HPV infenction on cervix were tested for HPV genotypes by flow-throughhybridization and gene chip(HybriMax). In Part Ⅱ，The HPV L1capsid protein incytologic specimens of the cervix was detected by using Immunocytochemistry in301women treated in the Xinjiang Uighur Autonomous Region People's hospital fromNovember2011to October2012.after diagnosis were confirmed According tohistological biopsy, Uighur women with chronic cervicitis were64cases (49%), CIN124cases (19%), CIN2/326cases (20%), cervical cancer15cases (12%). Han womenwith chronic cervicitis were83cases (48%), CIN139cases (23%) of CINⅠ/Ⅱ9cases(23%), cervical cancer10cases (6%). In Part III， Multiplex real-time polymerase chainreaction(PCR) was used to quantity the copy numbers of E2and E6genes of HP V16insamples of cervix of Uighur women with chronic cervicitis were16cases (22%), CINⅠ6cases (11%), CINⅡ8cases (11%), CIN Ⅲ21cases (29%)，cervical cancer21cases(29%). Han women with chronic cervicitis were13cases (25%), CINⅠ8cases (16%) ofCINⅡ9cases (17%), CIN Ⅲ9cases (17%)，cervical cancer13cases (25%). then by theE2/E6ratio,we could conclude the physical status of HPV-16in cervical sample inUighur and Han women. Results: Apart from HPV-16、18，the most common HPVtype in Uighur women were HPV52、53、58、39、68，31、66、56、6and11。in Hanwomen wereHPV52、58、53、31、33、68、66、39、45、11、6and CP8304.Single infection was dominant in both Uighur and Han women, multiple infection was less; The positiveexpression rate of HPV L1capsid protein in Uighur women was39%(25/64) in chroniccervicitis，CINⅠ62.5%(15/24), CINⅡ/Ⅲ27%(7/26)，no expression in cervicalcancer.There was significant differences in Uighur women (P <0.05). In Hanwomen L1protein expression was41%(34/83) in chronic cervicitis， CIN156%(22/39), CIN2/331%(11/39), no expression in cervical cancer,There was significantdifferences in Han women (P <0.05) and there were No statistically significant differencebetween the Uyghur women and Han women(P＞0.05)。Both in Uighur and Hanwomen, The HPV16integration rate was increased with the severity of cervical lesions，But there was no statistically significant difference(P>0.05). Also there was no statisticallysignificant difference(P>0.05) between Uighur and Han women in. the physical status ofHPV16.Conclusion: HPV16is most common HPV type in chronic cervicitis, CIN andcervical carcinoma both in Uighur and Han；The positive rate of HPV L1capsid proteinis decreased with the lesion progression from CIN1to CIN2/3to cervical cancer andexpected to become biomarkers to predict the progression of cervical lesion. Therewere no differences between Uighur and Han women in the expression of HPV L1protein. HPV L1protein expression in Han and Uighur women had no diffidence。There was no statistically significant difference(P>0.05) between the physical status ofHPV-16in Uighur and in Han women.
Objective: To investigate the distribution and significance of the HPV16in chroniccervicitis, Cervical intraepithelial neoplasia (CIN) and cervical carcinoma. To evaluate theexpression and clinical significance of human papilloma virus (HPV) L1capsid protein incytologic specimens of the cervix from HPV-positive Uighur and Han women. Todetect physical status of human papillomavirus(HPV)16in cervical lesions tissue inUighur women in Xinjiang so as to explore the relation with Severity of cervical lesionsXinjiang Uighur women and Han women in China. Methods: In Part Ⅰ，428patientswith Hr HPV infenction on cervix were tested for HPV genotypes by flow-throughhybridization and gene chip(HybriMax). In Part Ⅱ，The HPV L1capsid protein incytologic specimens of the cervix was detected by using Immunocytochemistry in301women treated in the Xinjiang Uighur Autonomous Region People's hospital fromNovember2011to October2012.after diagnosis were confirmed According tohistological biopsy, Uighur women with chronic cervicitis were64cases (49%), CIN124cases (19%), CIN2/326cases (20%), cervical cancer15cases (12%). Han womenwith chronic cervicitis were83cases (48%), CIN139cases (23%) of CINⅠ/Ⅱ9cases(23%), cervical cancer10cases (6%). In Part III， Multiplex real-time polymerase chainreaction(PCR) was used to quantity the copy numbers of E2and E6genes of HP V16insamples of cervix of Uighur women with chronic cervicitis were16cases (22%), CINⅠ6cases (11%), CINⅡ8cases (11%), CIN Ⅲ21cases (29%)，cervical cancer21cases(29%). Han women with chronic cervicitis were13cases (25%), CINⅠ8cases (16%) ofCINⅡ9cases (17%), CIN Ⅲ9cases (17%)，cervical cancer13cases (25%). then by theE2/E6ratio,we could conclude the physical status of HPV-16in cervical sample inUighur and Han women. Results: Apart from HPV-16、18，the most common HPVtype in Uighur women were HPV52、53、58、39、68，31、66、56、6and11。in Hanwomen wereHPV52、58、53、31、33、68、66、39、45、11、6and CP8304.Single infection was dominant in both Uighur and Han women, multiple infection was less; The positiveexpression rate of HPV L1capsid protein in Uighur women was39%(25/64) in chroniccervicitis，CINⅠ62.5%(15/24), CINⅡ/Ⅲ27%(7/26)，no expression in cervicalcancer.There was significant differences in Uighur women (P <0.05). In Hanwomen L1protein expression was41%(34/83) in chronic cervicitis， CIN156%(22/39), CIN2/331%(11/39), no expression in cervical cancer,There was significantdifferences in Han women (P <0.05) and there were No statistically significant differencebetween the Uyghur women and Han women(P＞0.05)。Both in Uighur and Hanwomen, The HPV16integration rate was increased with the severity of cervical lesions，But there was no statistically significant difference(P>0.05). Also there was no statisticallysignificant difference(P>0.05) between Uighur and Han women in. the physical status ofHPV16.Conclusion: HPV16is most common HPV type in chronic cervicitis, CIN andcervical carcinoma both in Uighur and Han；The positive rate of HPV L1capsid proteinis decreased with the lesion progression from CIN1to CIN2/3to cervical cancer andexpected to become biomarkers to predict the progression of cervical lesion. Therewere no differences between Uighur and Han women in the expression of HPV L1protein. HPV L1protein expression in Han and Uighur women had no diffidence。There was no statistically significant difference(P>0.05) between the physical status ofHPV-16in Uighur and in Han women.
引文
[1] Ferlay, P Autier, M Boniol, M Heanue, M Colombet and P Boyle. Estimates of the cancerincidence and mortality in Europe in2006.[J] Annals Oncol.2007;18（3）:581–592.
[2] Arbyn, X. Castellsague, S. de Sanjose.Worldwide burden of cervical cancer in2008.[J]Annals of Oncology.22:2675–2686,2011.
[3]马松,安琳.1996-2005年中国女性宫颈癌死亡水平研究.现代预防医学.2009；36（1）：47-50.
[4]姜淑清,土送爱,周俊兰,等.新疆策勒县妇女病现状调查与分析[J].中国妇幼保健,2006,21(4):524-526.
[5]拉莱苏祖克,彭玉华,周康,房新志,王丽.新疆不同民族子宫颈癌发病趋势分析[J].新疆医科大学学报.2006；29(7)：569-571.
[6]张国庆,刘开江,赖小军,等.新医大附属肿瘤医院1989~2002年住院病人恶性肿瘤分布[J].新疆医科大学学报,2003,26(4)：393-394.
[7] Zur Hausen H，de Villiers EM，Gissmann L.Papilloma-virus infections and humangenital cancer［J］.GynecolOncol，1981,12: S124-128．
[8] Zur Hausen H．Immortalization of human cells and theirmalignant conversion by highrisk human papillomavirus genotypes In;1999: Elsevier;1999:405-411．
[9] deVilliersEM, auquetC, BrokerTR, et a.l Classification ofpapillomaviruses[J]. Virology,2004,324(1):17-27·
[10]Doorbar J.Molecular biology of human papillomavirus in fection and cervical cancer[J]. Clinical Science (2006)110,(525–541).
[11]Bouvard V, Baan R, Straif K, Grosse Y, Secretan B,El Ghissassi F, et al. A review ofhuman carcinogens-PartB: biological agents. Lancet Oncol.2009;10:321-2.
[12]MufiozN, BoschFX, des Setal.International Agency for search on CanCerMultieenter Cervieal Cancer Study Group.EP idemiologie N Eng [J] Med.2003;348:518一527.
[13]Clifford GM,Smith JS,Plummer M etal.Human Papillomavirus typ esininvasiveeerviea leaner world wide meta analysis.Br [J] Caneer2003:88:63一73.
[14]ZhaoY,LinH,ShenDetal.Distribution of HPV genotype esinuter in ervical lesions inYanbian,northern China.Pathol Int.2008;58:643一7
[15]HongD,YeF,ChenH,etal. Distribution of human Papillomavirus genotype esin thePatients with eerviea lear cinomaandits Precursorsin Zhejiang Province,China.Int [J]Gyneeol Caneer.2008.18:104一109.
[16]G M Clifford SG，R Herrero,N Muoz,P J F Snijders,and the IARC HPV PrevalenceSurveys Study Group.Worldwide distribution of humanpapillomavirus types incytologically normal women in the International Agency for Research on CancerHPV preva-lence surveys: a pooled analysis［J］．Lancet，2005．
[17]玛依努尔·尼牙孜,李丽,陈凤,章文华,朱开春,刘新伟,热孜亚·买买提孜,孙振柱,赵丽霞,张询,潘秦镜,刘新伏,武艳萍,乔友林.新疆维吾尔族女性人乳头瘤病毒感染与宫颈癌相关性的流行病学调查［J］.临床肿瘤学杂志2011年4月第16卷第4期。
[18]李霓,代敏.中国妇女人乳头瘤状病毒感染的多中心横断面研究.[J]中华疾病控制杂志.2008；12（5）：411-415.
[19]陈凤,曾转萍,刘彬,黄曼妮,张洵,潘秦镜,章文华,赵芳辉,戎寿德,乔友林.山西省阳城县妇女人乳头瘤病毒感染的危险因素分析.[J]实用肿瘤杂志.2004；19(4):349-351.
[20]Wen Chen, Xun Zhang, Anco Molijn, Mayinuer Niyazi et al. Human papillomavirustype-distribution in cervical cancerin China: the importance of HPV16and18[J].Cancer Causes Control (2009)20:1705–1713
[21]Clifford GM, Gallus S, Herrero R, et al. Worldwide distribution ofhumanpapillomavirus types in cytologically normal women in the In-ternational Agency forResearch on Cancer HPV prevalence surveys:a pooled analysis [J]. Lancet,2005,366(9490):991-998.
[22]鲍彦平,李霓,王鹤等.中国妇女子宫颈乳头瘤病毒型别分布的Meta分析[J].中华流行病学杂志，2007，28，（10）：6.
[23]de Sanjose S,Quint WG, Alemany L, et al. Human papillomavirus genotype attributionin invasive cervical cancer: a retrospective cross-sectional worldwide study.[J]Lancet Oncol.2010;11:1048-1056.
[24]Guzhalinuer ABLZ,Cheng JX. The spectrum of HPV infection inXinjiang Uighurwomen with cerv ica l cancer [J]. Tumor,2007,27(5):379-382(In Chinese).
[25]Cates, W., Jr.1999. Estimates of the incidence and prevalence of sexually transmitteddiseases in the United States[J]. Sex Transm. Dis.26(4Suppl.):S2–S7.
[26]RuudL,M.Bkkers.Epidemiological and clinical aspects of human papillomavirusdetection in the preverition of cervical cancer [J].Rev Med Virol2004，14:95一105.
[27]黄志红,钱德英,王丁等.人乳头状瘤病毒负荷量与宫颈癌以及宫颈癌前病变的相关研究[J].中国妇幼保健，2006，21(11):1557-1559
[28]Zheng ZM,Baker CC.Papillomavirus genome structure,expression,andpost-transcriptional regulation.[J]Front Biosci.2006;11:2286-302.
[29]OsterAG.Natural history of cervical intraepithelial neoplasia: a critical review[J].Int JGynecol Pathol,1993,12(2):186
[30]Moscicki AB, Schiffman M, Kjaer S, et al. Chapter5:Updating the natural history ofHPV and anogenital cancer.[J] Vaccine2006;24(Suppl3):42-51.
[31]Peto, C. Gilham, O. Fletcher and F.E. Matthews, Thecervical cancer epidemic thatscreening has prevented in the UK,[J] Lancet364(2004),249–256.
[32]Baak JP, Kruse AJ,Janssen E,van Diermen B. Predictive testing ofearly CINbehaviour by molecular biomarkers.[J] Cell Oncol2005;27:277–80
[33]Wright TC Jr, Schiffman M. Adding a test for human papillomavirus DNA tocervical-cancer screening. N Engl [J] Med.2003;348:489-490.
[34]Schiffman M, Castle PE, Jeronimo J, et al. Human papillomavirus and cervical cancer.[J] Lancet.2007;370:890-907.
[35]Saslow D, Solomon D, Lawson HW,et al:American Cancer Society, American Societyfor Colposcopy and Cervical Pathology, and American So-ciety for ClinicalPathology screening guidelines forthe prevention and early detection of cervicalcancer.[J]CA Cancer Clin62:147-172,2012.
[36]Saslow D, Solomon D, Lawson HW, et al:American Cancer Society, AmericanSociety for Col-poscopy and Cervical Pathology, and American Soci-ety for ClinicalPathology Screening Guidelines for theprevention and early detection of cervicalcancer.[J]Low Genit Tract Dis [epub ahead of print onMarch13,2012].
[37]Mayrand MH, Duarte-Franco E,Rodrigues I,et al: Human papillomavirus DNA versusPapanico-laou screening tests for cervical cancer.[J]N EnglMed357:1579-1588,2007.
[38]Bulkmans NW, Berkhof J, Rozendaal L, etal: Human papillomavirus DNA testing forthe detection of cervical intraepithelial neoplasia grade3and cancer:5-yearfollow-up of a ran-domised controlled implementation trial.[J] Lancet370:1764-1772,2007.
[39]Naucler P, Ryd W, To¨ rnberg S, et al: Humanpapillomavirus and Papanicolaou teststo screenfor cervical cancer. N Engl J Med357:1589-1597,2007
[40]Ronco G, Giorgi-Rossi P, Carozzi F, et al:Efficacy of human papillomavirus testing forthedetection of invasive cervical cancers and cervicalintraepithelial neoplasia: Arandomised controlledtrial.[J]Lancet Oncol11:249-257,2010.
[41]Anttila A, Kotaniemi-Talonen L, Leinonen M,et al: Rate of cervical cancer, severeintraepithelial neoplasia, and adenocarcinoma in situ in primaryHPV DNA screeningwith cytology triage: Ran-domised study within organised screening pro-gramme.BMJ340:c1804,2010.
[42]Cuzick J, Clavel C, Petry KU, et al: Overviewof the European and North Americanstudies on HPVtesting in primary cervical cancer screening.[J] Int Cancer119:1095-1101,2006.
[43]Ronco G, Giorgi-Rossi P, Carozzi F, et al:Results at recruitment from a randomizedcontrolledtrial comparing human papillomavirus testing alonewith conventionalcytology as the primary cervicalcancer screening test.[J]Natl Cancer Inst100:492-501,2008.
[44]Sankaranarayanan R, Nene BM, Shastri SS, etal: HPV screening for cervical cancer inrural India.[j]N Engl Med360:1385-1394,2009.
[45]Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human papillomavirustesting, and risk for cervical neoplasia: a10-year cohort analysis.[J] Natl Cancer Inst.2003;95:46-52.
[46]Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology andhuman papillomavirus testing in cervical cancer screening: joint European cohortstudy. BMJ.2008;337:a1754.
[47]Schiffman M, Glass AG, Wentzensen N, et al. A long-term prospective study oftype-specific human papillomavirus infection and risk of cervical neoplasia among20,000women in the Portland Kaiser Cohort Study.[J] Cancer EpidemiolBiomarkers Prev.2011;20:1398-1409.
[48]Raquel Ibá ez, Judit Moreno-Crespi, Montserrat Sardà, et al. Prediction of cervicalintraepithelial neoplasia grade2+(CIN2+) using HPV DNA testing after adiagnosisof atypical squamous cell of undeterminedsignificance (ASC-US) inCatalonia, Spain ［J］BMC Infectious Diseases2012,12:25.
[49]Song H, Moseley PL, Lowe SL, et al. Inducible heat shock protein70enhancesHPV31viral genome replication and virion production during the differentiation-dependent life cycle in human keratinocytes［J］. Virus Res,2010,147（1）:113-122.
[50]Gagnon D,Joubert S, Sénéchal H, et al. Proteasomal degradation ofthe papillomavirusE2protein is inhibited by overexpression of bro-modomain-containing protein4［J］J Virol,2009,83（9）:4127-4139.
[51]Lurchachaiwong W,Junyangdikul P,Termrungruanglert W,et al.Whole genomesequence analysis of human papillomavirus type18from infected Thai women ［J］Clin Pathol.2010,53（3）:161-166.
[52]Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53and Gene ExpressionProfiling. Buitrago-Perez A, Garaulet G, Vazquez-Carballo A, Paramio JM, andGarcia-Escudero R. Curr Genomics, Mar ［J］Clin Pathol2009;10(1):26-34.
[53]Mark H. Stoler, Thomas C. Wright Jr, Abha Sharma,,et al. High-Risk HumanPapillomavirus Testing in Women With ASC-US CytologyResults From theATHENA HPV Study. Am [J] Clin Pathol2011;135:468-4757F
[54]Moberg M, Gustavsson I, Wilander E, et al. High viral loads of humanpapillomavirous predict risk of invasive cervical carcinoma [J]. Br J Cancer,2005,92(5):891-894.
[55]Samuel R, Francois C, Dan Fontaine, James B, Nicholas E, Prafull G, Veeresh G, GlenH, Elias B, Nick K, Christopher G, and Adrian L. Aptima HPV E6/E7mRNA Test Isas Sensitive as Hybrid Capture2Assay but More Specific at Detecting CervicalPrecancer and Cancer.[J] Clin Microbiol.2011;49(2):557-564.
[56]Jonathan H, Abul E, Erin S, Domenico Co, Bridgett R, and David S. HPV L1CapsidProtein Detection and Progression of Anal Squamous Neoplasia.Am [J] Clin Pathol,2011;135(5):436-441.
[57]Stuart IC, Christothea CW, Kaisheng W, Lawrence S. Young, Sally R, Paul G. Murray,and Ciaran B.J. Disruption of the E2Gene Is a Common and Early Event in theNatural History of Cervical Human Papillomavirus Infection: A Longitudinal CohortStudy.[J]Cancer Res. May2009;69:3828-3832.
[58]Ga lle AVB,Ina HB, Christophe ED, Caroline AJH, Marc A, Niel H, Annie JV, andJohannes JB.Human Papillomavirus16Load and E2/E6Ratio in HPV16-PositiveWomen: Biomarkers for Cervical Intraepithelial Neoplasia2in a Liquid-BasedCytology Setting.[J]Cancer Epidemiol. Biomarkers Prev. Nov2009;18:2992-2999.
[59]Brooke C, Nicole B, and Scott BVP.Human Papillomavirus E6Regulates theCytoskeleton Dynamics of Keratinocytes through Targeted Degradation of p53.[J]Virol. Nov2007;81:12675-12679.
[60]Kate C and Nicolas W.Human Papillomavirus mRNA and p16Detection asBiomarkers for the Improved Diagnosis of Cervical Neoplasia. Cancer Epidemiol.[J]Biomarkers Prev. Oct2008;17:2536-2545.
[61]Dimitrios H, George AP, George DV, Alexandros R, Sonia M, Zannis V, Emmanuel D,and Aris A. p16INK4A Is a Strong Biomarker for Cervical Intraepithelial Neoplasiaand Invasive Cervical Carcinoma: A Reappraisal.[J]Reproductive Sciences, Jul2009;16:685–693
[62]J de Wilde, SM Wilting, CJ Meijer, MA van de Wiel, B Ylstra, PJ Snijders, and RDSteenbergen. Gene expression profiling to identify markers associated withderegulated hTERT in HPV-transformed keratinocytes and cervical cancer. Int [J]Cancer, Feb2008;122(4):877-888.
[63]李慧弘,肖长义. HPV DNA整合,E2破坏,HPV E2/E6比值与宫颈癌关系的研究.[J]中国免疫学杂志,2010；26（7）：670-673.
[64]时艳梅,叶红,肖长义,陈建玲,王雅琴,吴江峰.宫颈病变患者病变组织HPV整合状态的变化及意义.[J]山东医药.2009；（49）6：1-3.
[65]肖巍,卞美璐,马莉,刘军,陈颖.子宫颈液基细胞学检查异常的涂片中人乳头状瘤病毒L1蛋白的表达及其意义.[J]中华妇产科杂志.2009,44（12）：887-891.
[66]Ordonez RM, Espinosa AM, Sanchez–Gonzalez DJ et al. Enhanced oncogenicity ofAsian-American human papillomavirus16is associated with impaired E2repressionof E6/E7oncogene transcription.[J]Gen Virol,2004；85(6):1433-1444
[67]PettM, Coleman N. Integration of high-risk human papillomavir-us: a key event incervical carcinogenesis?[J]. J Patho,l2007,212(4):356-367.
[68]Vinokurova S, Wentzensen N, Kraus I, et a.l Type-dependent in-tegration frequencyofhuman papillomavirusgenomes in cervical le-sions[J].CancerRes,2008,68(1):307-313.
[69]WentzensenN, Vinokurova S, DoeberitzMV. Systematic review ofgenomic integrationsites of human papillomavirus genomes in epi-thelial dysplasia and invasive cancerof the female lower genitaltract[J]. CancerRes,2004,64(11):3878-3884.
[70]Henrik Griesser, Heinz Sander, Cindy Walczak, et al. HPV Vaccine Protein L1Predicts Disease Outcome of High-Risk HPV+Early Squamous DysplasticLesions.Am J Clin Pathol[J]. CancerRes2009,132:840-845.
[71] Castellsague X,Diaz M,de Sanjose S,et al. Worldwide human papillomavirus etiologyof cervical adenocarcinoma and its cofactors: implications for screening andprevention [J]. Natl Cancer Inst.2006Mar1;98(5):303-315
[72]李瑞珍,石菊芳,周庆芝等.应用基因芯片技术检测高危型人乳头瘤病毒在宫颈癌筛查中的评价[J].中华医学杂志,2006,86(5):307-311
[73]Kim KH,Yoon MS,Na YJ,et al.Development and evaluation of a highly sensitivehuman papillomavirus genotyping DNA chip[J].Gynecol Oncol.2006Jan；100(1):38-43
[74]Choi YD,JungWW,Nam JH,et al.Detection of HPV genotypes in cervical lesions bythe HPV DNA chip and sequencing[J].Gynecol Oncol,2005,98(3):369-375.
[75]李瑞珍,石菊芳,周庆芝等.应用基因芯片技术检测高危型人乳头瘤病毒在宫颈癌筛查中的评价[J]巾华医学杂志,2006,86(5):307-311
[76] Kim KH,Yoon MS,Na YJ,et al. Development and evaluation of a highly sensitivehuman papillomavirus genotyping DNA chip [J].ynecol Oncol.2006Jan;100(1):38-43
[77] Choi YD,JungWW,Nam JH,et al. Detection of HPV genotypes in cervical lesions bythe HPV DNA chip and sequencing[J]. Gynecol Oncol,2005,98(3):369-375
[78] Masumoto N, Fujii T, Ishikawa M, et al·Dominant humanpapillomavirus16infectionin cervical neoplasia in young Japanesewomen; study of881outpatients·[J]GynecolOnco,l2004,94:509-514·
[79] Stanczuk GA, Kay P, Sibanda E,et al·Typing of humanpapillomavirus in Zimbabweanpatients with invasive cancer of theuterine cervix·[J]ActaObstet Gynecol Scand,2003,82:762-766·
[80].Dalstein V, Riethmuller D, Pretet J L,et al.·Persistence and load of high-risk HPV arepredictors for development of high-grade cervical lesions: a longitudinal Frenchcohort study［J］.Int J Cancer,2003,106(3):396-403。
[81]乐杰,主编.妇产科学.第7版.北京:人民卫生出版社,2008.262-263
[82] Tavassoli F A,Devilee P. WHO classification of tumor. Pathology genetics of tumorsof the breast and female genital organs[M].Lyon: IARC Press,2003:262
[83] Cox J T. Human pap illomavirus testing in p rimary cervical screening and abnormalpapanicolaou management [J]. Obstet Gynecol Surv,2006,6191:15–25
[84]Clifford GM,Swith JS,PlummerM,eta.l Human papillomavius types in iuvasivecervica cancerworldwide:a weta-analysis [J]. Br J Cancer,2003,88:63-73.
[85]Smith JS,Lindsay L,HootsB et a.l Human papillomavirus type dis-tribution in invasivecervical cancer and high-grade cervical lesions: ameta-analysis updat[J]. Int JCancer,2007,121(3):621.
[86]BaoYP, LiN, Smith JS, et a.l Human papillomavirus type-distribu-tion in the cervix ofchinesewomen: ameta-analysis [J]. Int J STDA IDS,2008,19(2):106.
[87]Wheeler CM,Hunt WC,Joste NE, et al. Human papillomavirus geno-type distributions:implications for vaccination and cancer screening in the United States.[J] NatlCancer Inst.2009;101(7):475–487.
[88]CoglianoV,Baan R,StraifK,et a.l Carcinogenicity ofHuman papillo-mavius[J].LancetOnco,l2005,6(4):204.
[89] Harper DM,Franco EL,Wheeler CM,Moscicki AB,RomanowskiB,Roteli-Martins CM,Jenkins D,Schuind A,Costa Clemens SA,Dubin G. Sustained efficacy up to4–5yearsof a bivalent L1virus-like particle vaccine against human papillomavirus types16and18:follow-up from a randomised control trial.[J]Lancet2006;367:1247–55.
[90] Villa LL,Costa RL,Petta CA,Andrade RP,Ault KA,Giuliano AR,Wheeler CM,Koutsky LA,Malm C,Lehtinin M,Skjeldestad FE,Olsson SE,et al.Prophylacticquadrivalent human papilloma-virus (types6,11,16and18) L1virus-like particlevaccine in youngwomen: a randomised double-blind placebo-controlledmulticentrephase II efficacy trial.[J]Lancet Oncol2005;6:271–8.
[91] Anil K.Chaturvedi,Hormuzd A.Katki,Allan Hildesheim, Ana Cecilia Rodr!guez,Wim Quint,Mark Schiffman,Leen-Jan Van Doorn,Carolina Porras,Sholom Wacholder,Paula Gonzalez,Mark E.Sherman and Rolando Herrero for the CVT Groupb.HumanPapillomavirus Infection with MultipleTypes:Pattern of Coinfection and Risk ofCervical Disease.[J]ID2011:203
[92] Eiben GL,da Silva DM,Fausch SC,et al. Cervical cancer vaccines: recent advances inHPV research [J] Viral Immunol,2003,16(2):111-121
[93] Guzhalinuer ABLZ, Cheng JX. The spectrum of HPV infection inXinjiang Uighurwomen with cerv ica l cancer [J] Tumor,2007,27(5):379-382(In Chinese).
[94]张向楠,王英红,张文杰,李文婷,刘莹,张岚.新疆维吾尔族及汉族宫颈癌及高危癌前病变与HPV感染亚型关系研究.[J]中华实用诊断与治疗杂志2012年4月第26卷第4期.
[95]Susanne K. Kj r,Kirsten Frederiksen,Christian Munk,Thomas Iftner Long-termAbsolute Risk of Cervical Intraepithelial Neoplasia Grade3or Worse FollowingHuman Papillomavirus Infection: Role of Persistence.[j]. JNCI Vol.102, Issue19October6,2010.
[96] Clifford GM，Smith JS,Plummer M,et al． Human papil-lomavirus types in invasivecervical cancer worldwide: ameta－analysis[J] Br J Cancer,2003(1):63－73．
[97] Clifford GM,Smith JS,Plummer M,et al. Human papil-lomavirus types in invasivecervical cancer worldwide:ameta－analysis[J]Br J Cancer,2003(1):63－73.
[98]苏锡康,崔金环,杨光,等.宫颈癌组织中人乳头瘤病毒基因分型的研究［J］医学临床研究,2008(6):988－990.
[99]古扎丽努尔·阿不力孜,彭芝兰,刘珊玲等.HPV及其亚型在四川西北地区汉族及新疆南部地区维吾尔族妇女宫颈癌组织中的差异表达［J］中华微生物学和免疫学杂志,2004(5):408．
[100]古扎丽努尔·阿不力孜;帕提曼·米吉提;李庭芳;程静新;李华;路玲HPV各亚型在新疆各地区维吾尔族宫颈癌患者中的分布研究.[j].新疆医科大学学报.2009年第05期
[101]郑义,高丽敏,井明霞,张金丽,芮东升,王英红,阿曼古丽何玲赵娟杨磊.新疆维族妇女感染的HPV型别分布的研究.[J]现代生物医学进展Vol.12NO.1JAN.2012.
[102]杨英捷,赵健.2285例女性下生殖道人乳头状瘤病毒感染筛查结果分析[J]中国实用妇科与产科杂志,2006，(6):444－445.
[103]韩定英,吴洁,姜碧卿,等.深圳市罗湖区1420例妇女生殖道人乳头瘤病毒筛查结果分析[J]中国初级卫生保健,2008，22(2):42－43.
[104]靳琼,沈铿,李辉,等.西藏自治区妇女子宫颈人乳头状瘤病毒感染现状调查及相关因素分析[J].中华妇产科杂志，2009,44(12):898－902.
[105]胡庆兰,刘永珠,朱伟艳,唐霓,黄振勇,胡国洪.5000例宫颈细胞人乳头状瘤病毒感染筛查结果分析.[J]现代医院2012年2月第12卷第2期103-146.
[106] Clifford GM,Smith JS, PlummerM,et a.l Human papillomavirustypes in invasivecervical cancerworldwide: ameta-analysis[J]. Br Cancer,2003,88(1):63-73.
[107] Laia Bruni,Mireia Diaz,Xavier Castellsague′,Elena Ferrer,F. Xavier Bosch,andSilvia de Sanjose′Cervical Human Papillomavirus Prevalencein5Continents:Meta-Analysis of1Million Womenwith Normal Cytological Findings.[j]TheJournal of Infectious Diseases2010;202(12):1789–1799.
[108]李霓,张思维,陈万青,等.亚洲妇女宫颈癌中人乳头状瘤病毒型别分布的Meta分析[J].中国肿瘤,2010,(3):195-202.
[109] Kazunari Kondo, Asami Uenoyama, Ryo Kitagawa, Hajime Tsunoda, RikaKusumoto-Matsuo, Seiichiro Mori,2Yoshiyuki Ishii, Takamasa Takeuchi,Tadahito Kanda, and Iwao Kukimoto.Genotype Distribution of HumanPapillomaviruses in Japanese Women with Abnormal Cervical Cytology. OpenVirol [J]. Clinica Chimica Acta2012;6:277–283.
[110]Yong Shen, Jiao-Mei Gong,Yan-Qing Li, Yu-Mei Gong, Dong-Mei Lei, Guo-MeiCheng,Xiao-Fu Li.Epidemiology and genotype distribution of humanpapillomavirus (HPV) in women of Henan Province, China.[J]. Clinica ChimicaActa.Volume415,16January2013, Pages297–301.
[111]王又又,向群英,佘茜,谭云,等。宫颈癌高发区妇女HPV感染及影响因素分析。[J]中国公共卫生2011年3月第27卷第3期。
[112] Wheeler CM,Castellsague X, Garland SM,et al.Cross-protective efficacy ofHPV-16/18AS04-adjuvanted vaccine against cervical infection and precancercaused by non-vaccine oncogenic HPV types:4-year end-of-study analysis of therandomised, double-blind PATRICI Atrial.[J]Lancet Oncol.2012;13:100–110.
[113] Kovács K, Varnai AD, Bollmann M, et al. Prevalence and geno type distribution ofmultiple human papillomavirus infection in theuterine cervix: a7.5-yearlongitudinal study in a routine cytolo gy-based screening population in WestGermany[J]. J Med Virol,2008,80(10):1814-1823.
[114]陶萍萍,卞美璐,李敏,等.HPV多重感染与宫颈病变关系探讨[J]中国妇产科临床杂志2006年3月(7):94-96.
[115] Sowjanya AP,Jain M,Poli UR,et al.Prevalence and distribution of high-riskhumanpapilloma virus(HPV)types in invasive squamous cell carcinoma of thecervix andin normal women in Andhra Pradesh,India[J].BMC Infect Dis.2005Dec22；5:116
[116] Sanchez-Anguiano LF,Alvarado-Esquvel C,Reyes-Romero MA,et al.Humanpapillomavirus infections in women seeking cervical Papanicolaou cytology ofDurango,Mexico:prevalence and genotypes[J].BMC Infect Dis.2006Feb20；
[117] Ciotti M,Paba P,Bonifacio D,et al.Single or multiple HPV types in cervical cancerand associated metastases[J].Oncol Rep.2006Jan；15(1):143-148
[118] Lee SA,Kang D,Seo SS,et a.l Multiple HPV infection in cervicalcancer screenedbyHPV DNA chip[J].CancerLett,2003,198(2):
[119]王维鹏我院妇女宫颈感染高危型人乳头瘤病毒基因型分布[J].实用医学杂志,2007,23(13):2040-2041.
[120] Bao YP,Li N.Smith JS.et a1.Humanpapillomavirus type distribution in women fromAsia:a meta—analysis.[J] Gynecol Cancer,2008,18：7I-79.
[121]An HJ, Cho NH,Lee SY,et al. Correlationof cervical carcinoma andprecancerouslesions wit h human papilliomavirus (HPV) genotypes detected with the HPV DNA chip microar2ray met hod[J]. Cancer,2003,97(7):1672-1680.
[122] Munoz N,Bosch FX,Sanjose S D,et al. Epidemiologic classification of humanpapillomavirus types associated wit h cervical cancer[J].N Engl J Med,2003,348(6):518-527.
[123] Kay P,Soeters R,Nevin J,et al.High prevalence of HPV16in South African womenwit h cancer of t he cervix and cervical int raepit helial neoplasia[J]. MedVirol,2003,71(2):265-273
[124]吕虹,刘志忠,刘竞争,等.人乳头瘤病毒基因分型检测在绝经后妇女HPV感染中的应用价值[J].中国老年学杂志,2011,31(11):2117-2118.
[125] TANG Y, ZHANG J, FANG CY, et al. Correlation analysis ofcervical intraepithelialneoplasia and HR-HPV infection inmarried women in Fengtai District[J]. ChineseJournal of Womanand Child Health Research,2011,22(4):418-419,422. Chi-nese
[126] Moscicki AB,Shiboski S,Hills NK,et al.Regression oflow-grade squamousintra-epithelial lesions in young wom-en[J].Lancet,2004,364(6):1678-1683.
[127] Ferlay J,Parkin DM,Curado MP,et al. Cancer Incidence in Five Continents.[J]International Agency for Research on Cancer2010, I to IX, April,2011.128-135.
[128] Dufresne S,Sauthier P,Mayrand MH, et al. Human Papillomavirus (HPV) DNATriage of Women with Atypical Squamous Cells of Undetermined Significance withAmplicor HPV and Hybrid Capture2Assays for Detection of High-GradeLesions of the Uterine Cervix.[J] Clin Microbiol2011,49(1):48-53.
[129] Ostensson E,Fr berg M,Hjerpe A,et al. Economic analysis of human papillomavirustriage, repeat cytology, and immediate colposcopy in management of women withminor cytological abnormalities in Sweden.[J]Acta Obstet Gynecol Scand2010,89(10):1316-1325.
[130] Raquel Ibá ez, Judit Moreno-Crespi,Montserrat Sardà,et al. Prediction of cervicalintraepithelial neoplasia grade2+(CIN2+) using HPV DNA testing after adiagnosisof atypical squamous cell of undeterminedsignificance (ASC-US) inCatalonia, Spain [J]BMC Infectious Diseases2012,12:25.
[131] Mark H. Stoler,Thomas C.Wright Jr,Abha Sharma,et al.High-Risk HumanPapillomavirus Testing in Women With ASC-US CytologyResults From theATHENA HPV Study.[J] Am J Clin Pathol2011;135:468-475
[132] Roberto Flores1,Mary Papenfuss1,Walter T. Klimecki2,et al.Cross-sectional analysisof oncogenic HPV viral load and cervical intraepithelial neoplasia. Int.[J] Cancer:118,1187–1193(2006).
[133] Jarboe EA,Venkat P, Hirsch M S,et al. A Weakly Positive Human PapillomavirusHybrid Capture II Result Correlates With a Significantly Lower Risk of CervicalIntraepithelial Neoplasia2,3After Atypical Squamous Cells of UndeterminedSignificance.[J]Cytology Journal of Lower Genital Tract Disease: July2010-Volume14-Issue3-pp174-178
[134] M.origoni,G.carminati,M.sider,et al.“Low-grade positivity” of HPV viral load afteratypical Squamous cells of undetermined significance (ASCUS) cytology identifieswomen at low-risk for cervical intraepithelial neoplasia grade2and3.[J] Europeanjournal of gynaecological oncology:vol.XXXⅢ,no.3,2102.
[135] Attila T Lorincz,Philip E Castle,Mark E Sherman,et al.Viral load of humanpapillomavirus and risk of CIN3or cervical cancer.[J]lancet.Volume360,Issue9328,20July2002, p228–229
[136] Hilfrich R,Hariri J.Prognostic relevance of human papillomavirus L1capsid proteindetection within mild and moderate dysplastic lesions of the cervix uteri incombination with p16biomarker[J]．Anal Quant Cytol Histol，2008，30(2):78-82．
[137]陈恒禧,甘晓玲,傅璟.HPV L1检测预测宫颈鳞状上皮内病变预后的意义[J].现代妇产科进展,2009,18(11):865-868.
[138]张佳立,郜红艺,张江宁,等.宫颈液基细胞HPV L1壳蛋白表达的临床意义[J].诊断病理学杂志,2010,17(6):456-459.
[139]黄斌,李瑞珍,吴瑞芳,等.HPV L1壳蛋白与hTERC基因检测及联合分析对宫颈癌筛查的意义[J].华中科技大学学报，2010,39(4):554-561.
[140] Siddiqui M T,Hornaman K,Cohen C,et al.ProEx C immunocyto-chemistry andhigh-risk human papillomavirus DNA testing in papan-icolaou tests with atypicalsquamous cell(ASC-US) cytology: correla-tion study with histologic biopsy[J]ArchPathol Lab Med,2008,132(10):1648-1652.
[141] Doorbar J,The papillomavirus life cycle[J].J Clin Virol,2005,32Suppl1: S7-15.
[142] Bousarghin L,Hubert P, Franzen E,et al.Human papillomavirus16virus-like particlesuse heparan sulfates to bind dendritic cellsand colocalize with langerin inLangerhans cells[J]. J Gen Virol,2005,86(5):1297-1305.
[143] Giroglou T,Florin L,Schafer F,et al. Human Papillomavirus In-fection Requires CellSurface Heparan Sulfate[J]. J Virol,2001,75(3):1565-1570.
[144] Yoon C S,Kim K D A,Park S N,et al.alpha(6) Integrin is themain receptor of humanpapillomavirus type16VLP.[J]Biochem Bio-phys Res Commun.2001,283(3):668-673.
[145] Evander M, Frazer I H,Payne E, et al. Identification of the al-pha6integrin as acandidate receptor for papillomaviruses[J]. J Virol,1997,71(3):2449-2456.
[146] Smith J L, Campos S K, Ozbun M A. Human papillomavirus type31uses acaveolin-1and dynamin-2mediated entry pathway forinfection of humankeratinocytes[J]. J Virol,2007,81(18):9922-9931.
[147] Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis ofsimian virus40reveals a new two-step vesicular-transport path-way to the ER [J]. Nat Cell Biol,2001,3(5):473-483.
[148] Block SL,Nolan T,Sattler C,et al.Comparison of theimmunogenicity andreactogenicity of a prophylacticquadrivalent humanpapillomavirus(types6,11,16,and18)L1virus－like particle vaccine in male andfemaleadoescents and young adult women[J]．Pediatrics，2006，118(5):2135-2145．
[149]郝敏]郝敏,卞美璐.人乳头瘤病毒L1蛋白功能及其临床应用[J].中国实用妇科与产科杂志,2010，26（5）：352－355.
[150] BontkesHJ, Ruizendaal JJ,Krammer D,et a.l Plasmacytoiddendritic cells arepresent in cervical carcinoma and become acti-vated by human papillomavirus type16virus like particles[J].GynecolOnco,l2005,96(3):897-901·
[151] PintolA,Castle PE, RodenRB, eta.l HPV16L1VLP vaccineelicits a broad spectrumof cytokine responses in whole blood[J].Vaccine,2005,23(27):3555-3564·
[152] Middleton K,Peh W, Southern S A, et al. Organisation of the hu-man papillomavirusproductive cycle during neoplastic progression provides a basis for the selection ofdiagnostic markers[J]. J Virol,2003,77(19):10186-10201.
[153]张佳立,郜红艺,张江宇,吴坤河,郭玉娟,李辉斌.宫颈液基细胞HPV L1壳蛋白表达的临床意义.[J]诊断病理学杂志2010年12月第17卷第6期.
[154] Webb E,Cox J,Cervical cancer causing human papillomaviruseshave an alternativeinitiation site for the L1protein[J]. VirusGenes，2005，30(1):31－35.
[155] Yoshida T,Sano T,Kanuma T,et al．Immunochemicalanalysisof HPV L1capsidprotein and p16protein in liq-uid－based cytologysamples from uterine cervicallesions[J].Cancer，2008，114(2):83-88．
[156] Rauber D,Mehlhom G,Fasching P A,et al.Prognostic significance ofthe detection ofhuman papilloma virus L1protein in smears of mild tomoderate cervicalintraepithelial lesions[J]Eur J Obstet Gynecol Re-prod Biol,2008,140(2):258-262.
[157] Griesser H, Sander H, H ilfrich R,et al. Correlation of im munochemical detection ofHPV L1capsid p rotein in papsmears with regression of high risk HPV positivemild/moderate dysplasia [J]. Anal Quant Cytol H istol,2004,26:2412245
[158]肖巍,卞美璐,马莉,刘军,陈颖.子宫颈液基细胞学检查异常的涂片中乳头状瘤病毒L1蛋白的表达其意义[J].中华妇产科杂志,2009,44(12):887-891.
[159]黄斌,李瑞珍,刘志红,等.HPV L1壳蛋白在宫颈脱落细胞中的表达及临床意义[J].华中科技大学学报:医学版,2009,38(6):824-828.
[160] Grit Mehlhorn,Ellen Obermann,Giovanni Negri,Lukas Bubendorf,ChristineMian,Martin Koch,Heinz Sander,Birgit Simm,Markus Lütge,ZsuzsannaBánrévi, Anke Weiss,Gieri Cathomas,Ralf Hilfrich,Matthias WilhelmBeckmann and Henrik Griesser.HPV L1detection discriminates cervical precancerfrom transient HPV infection: a prospective international multicenter study.[j].Modern Pathology.10.1038.l.2012.233-240.
[161] Boulet G,Horvath C,Vanden Broeck D,et al. Humanpapillomavirus:E6and E7oncogenes[J]. Int J Biochem CellBiol，2007，39(11):2006－2011.
[162] Yoshida T,Sano T,Kanuma T,et al. Immunochemical analysisof HPVL1capsidprotein and p16protein in liquid-based cytologysamples from uterine cervicallesions[J]. Cancer,2008,114(2):83－88.
[163] Kulmala SM,Syrjanen SM,Gyllensten UB,et al. Earlyintegration of high-copy HPV16detectable in women with normaland low-grade cervical cytology and histology[J]. Clin Pathol,2006,59(5):513－517.
[164] Block SL, Nolan T,Sattler C, et al.Comparison of theimmunogenicity andreactogenicity of a prophylactic quadrivalenthuman papillomavirus (types6,11,16,and18) L1virus-likeparticle vaccine in male and female adolescents andyoung adultwomen[J].Pediatrics,2006,118(5):2135-2145.
[165] Yoshida]Tomomi Yoshida.Immunochemical analysis of HPV L1capsid protein andP16proteinin liquid-based cytology samples from uterine cervical lesions[J].CancerCytopathol,2008,114:83-88
[166]刘朝齐,许雪梅,徐建青,等.人乳头瘤病毒16型晚期基因L1在原核细胞的表达及免疫效果观察[J].中国妇幼保健，2007,22:5028-5032.
[167] Melsheimer P.Immunocytochemical detection of HPV high-risk type L1capsidproteins in LSIL and HSIL as compared with detection of HPV L1DNA[J].Acta Cytol,2003,47:124-128
[168]潘保见,陈嘉薇,祝峰.宫颈鳞癌和癌前病变中eIF-4E表达及其与HPV16/18感染的关系[J].临床与实验病理学杂志,2007,23(5):528-531
[169] Dalstein V, Riethmuller D,Pretet J L,et al.·Persistence and load of high-risk HPVare predictors for development of high-grade cervical lesions: a longitudinal Frenchcohort study[J].Int J Cancer,2003,106(3):396-403.
[170] Moberg M,Gustavsson I,Gyllensten U.Real-time PCR based sys-tem forsimultaneous quantification of human papillomavirus typesassociated with high riskof cervical cancer.[J] Clin Microbiol,2003,41(7):3221-3228.
[171] Dalstein V,Riethmuller D,Pretet JL,et al. Persistence and load of high-risk HPVare predictors for development of high-grade cer-vical lesions: a longitudinalFrench cohort study． Int [J]Cancer,2003,106(3):396-403.
[172] L EE H,L EEK J,J UNQ C K,et al1Expression of HPV L1caspid protein in cervicalspecimens with HPV infection [J] Diagn Cytopathol,2008,36(12):86428671.
[173] Li W,Wang W,Si Met al.The physical state ofHPV16infection and it clinicalsignificance in cancer precursor lesion and cervical carcinoma[J].J Cancer Res ClinOncol,2008;134(12):1355-1361
[174] Huang L W,Chao S L,Lee B H.Integration of human papillomavirus type-16andtype-18is a very early event in cervical carcinogenesis[J].J Clin Pathol,2008;61(5):627-631.
[175] Matovina M,Sabol I,Grubisic Get al.Identification of human papillo-mavirustype16integration sites in high-grade precancerous cervical le-sions[J].GynecolOncol,2009;113(1):120-127.
[176] Pett M, Coleman N. Integration of high risk human papillomavirus: a key event incervical carcinogenesis.[J] The J of Pathol.,2007,212(4),356-367
[177] Tinelli A., Vergara D,Leo G, Malvasi A, Casciaro S,Leo E.et.al.Humanpapillomavirus genital infection in modern gynecology: genetic and genomicaspects.[J] Eur Clin in Obst and Gynaecol,2007,3(1),1-6
[178] Arias-Pulido H,Peyton C.L,Joste N.E,Vargas H,Wheeler C.M. Humanpapillomavirus type16integration in cervical carcinoma in situ and in invasivecervical cancer,[J] of Clin Microbiol.,2006,44(5),1755-62.
[179] Bosch, F. X., M. M. Manos, N. Munoz, M. Sherman, A. M. Jansen, J. Peto, M. H.Schiffman, V. Moreno, R. Kurman, K. V. Shah, et al.1995. Prevalence of humanpapillomavirus in cervical cancer: a worldwide perspective.[J] Natl. CancerInst.87796-802.
[180][Pirami L,Giache V, Becciolini A. Analysis of HPV16,18,31and35DNA inpre-invasive and invasive lesions of the uterine cervix.[J]Clin Pathol1997;50:600–4.
[181] Kalantari M,Blennow E,Hagmar B, et al. Physical state of HPV16and chromosomalmapping of the integrated form in cervical carcinomas.[J]Diagn Mol Pathol2001;10:46–54.
[182] Kristiansen E, Jenkins A,Holm R.Coexistence of episomal and integrated HPV16DNA in squamous cell carcinoma of the cervix.[J] Clin Pathol1994;47:253–6.
[183] Park JS,Hwang ES,Park SN,et al.Physical status and expression of HPV genes incervical cancers.[J]Gynecol Oncol1997;65:121–129.
[184] Dürst M, Kleinheinz A, Hotz M, et al. The physical state of human papillomavirustype16DNA in benign and malignant genital tumours.[J]Gen Virol1985;66:1515–22.
[185] Castellsague, X, F. X. Bosch,and N.Munoz.2002. Environmental co-factors in HPVcarcinogenesis.[J]Virus Res.89:191-199.
[186] Munoz, N, F. X. Bosch, S. de Sanjose, R. Herrero, X. Castellsague, K. V. Shah, P. J.Snijders, and C. J.Meijer.2003. Epidemiologic classification of humanpapillomavirustypesassociatedwith cervical cancer. N. Engl.[J]. Med.348:518-527.
[187] Munoz, N., F. X. Bosch, S. de Sanjose, R. Herrero, X. Castellsague, K. V. Shah, P. J.Snijders,andC.J.Meijer.2003.Epidemiologic classification of human papillomavirustypes associated with cervical cancer. N. Engl.[J]. Med.348:518-527.
[188] Pett, M, and N. Coleman.2007. Integration of high-risk human papillomavirus: akey event in cervical carcinogenesis?[J]. Pathol.212:356-367.
[189] Jeon, S, and P. F. Lambert.1995. Integration of human papillomavirus type16DNAinto the human genome leads to increased stability of E6and E7mRNAs:implications for cervical carcinogenesis. Proc. Natl. Acad. Sci. USA92:1654-1658.
[190] Romanczuk H, and P. M. Howley.1992. Disruption of either the E1or the E2regulatory gene of human papillomavirus type16increases viral immortalizationcapacity. Proc. Natl. Acad. Sci. USA89:3159-3163.
[191] Pett, M. R., W. O. Alazawi, I. Roberts, S. Dowen, D. I. Smith, M. A. Stanley, and N.Coleman.2004. Acquisition of high-level chromosomal instability is associatedwith integration of human papillomavirus type16in cervicalkeratinocytes.[J]Cancer Res.64:1359-1368.
[192] Jeon. S, B. L. Allen-Hoffmann, and P. F. Lambert.1995. Integration of humanpapillomavirus type16into the human genome correlates with a selective growthadvantage of cells.[J]. Virol.69:2989-2997.
[193] Moscicki AB,Shiboski S,Hills NK,et a1.Regression Of low·grade squamousintra—epithelial lesions in young women.[J] Lancet.2004;364:1678-1683.
[194] Saunier M,Monnier-BenoitS,Mauny F,et aL Analysis ofhuman papillomavirustype16(HPV I6)DNA load and physical state for identification of HPV16-infectedwomen with high-gradelesions or cervical carcinoma.[J] Clin Microbi01．2008；46：3678-3685.
[195] Li W,WangW,Si M,et a1.The physical state of HPVl6infection and its clinicalsignificance in cancer precursor lesion and cervical carcinoma.[J] Cancer Res ClinOnc01.2008;134:1355-1361.
[196] Mufioz N,Bosch FX,de Sanjos6S,et a1.International Agency for Research onCancer Multicenter Cervical Cancer Study Group.[J]Epidemiologic N Engl JMed.2003;348:518·527.
[197] Badaracco G, Venuti A, Sedati A, et a.l HPV216and HPV218in genital tumors:significantly different levels of viral integration and correlation to tumorinvasiveness[J]. JMed Viro,l2002,67:5742582.
[198] Molecular Signature of HPV-Induced Carcinogenesis: pRb,p53and GeneExpression Profiling. Buitrago-Perez A,Garaulet G, Vazquez-Carballo A, ParamioJM, and Garcia-Escudero R.[J]Curr Genomics, Mar2009;10(1):26-34.
[199] Hopman AH,Smedts F,DignefW,eta1.Transition ofhigh-grade Cervicalintraepithelialneoplasia to micro-invasive carcinoma is characterized by integrationof HPV16／18and numerical chromosome abnormalities．[J] Path01.2004,202:23-33.
[200] Cricca M,Morselli-Labate AM, Venturoli S, et a.l Viral DNA load, physical statusand E2/E6ratio asmarkers to gradeHPV16positive women for high-grade cervicallesions[J].GynecolOnco,l2007,106:549-557
[201] Briolat, J., V. Dalstein, M. Saunier, K. Joseph, S. Caudroy, J. L. Pretet, P. Birembaut,and C. Clavel.2007. HPV prevalence, viral load and physical state of HPV-16incervical smears of patients with different grades of CIN. Int.[J].Cancer121.2198-2204.
[202] Cricca, M, A. M. Morselli-Labate,S. Venturoli,S. Ambretti,G. A. Gentilomi,G.Gallinella,S. Costa, M. Musiani,and M. Zerbini.2007. Viral DNA load, physicalstatus and E2/E6ratio as markers to grade HPV16positive women for high-gradecervical lesions.[J] Gynecol. Oncol.106.549-557.
[203] Gallo, G., M. Bibbo, L. Bagella, A. Zamparelli, F. Sanseverino, M. R. Giovagnoli, A.Vecchione, and A. Giordano.2003. Study of viral integration of HPV-16in youngpatients with LSIL.[J] Clin. Pathol.56532-536.
[204] Kulmala, S. M., S. M. Syrjanen, U. B. Gyllensten, I. P. Shabalova, N. Petrovichev, P.Tosi, K. J. Syrjanen, and B. C. Johansson.2006. Early integration of high copyHPV16detectable in women with normal and low grade cervical cytology andhistology.[J] Clin. Pathol.59513-517.
[205]Ga lle A.V.Boulet,Ina H. Benoy,Christophe E. Depuydt,Caroline A.J. Horvath,1MarcAerts and Johannes J. Bogers. Human Papillomavirus16Load and E2/E6RatioinHPV16-Positive Women: Biomarkers for CervicalIntraepithelial Neoplasia≥2ina Liquid-BasedCytology Setting?.[J].Cancer Epidemiol Biomarkers Prev2009;18(11)
[206] Agne Sepetiene, Zivile Gudlevicien, Zana Bumbuliene, Grazina Drasutiene,Janina Didziapetriene.State of HPV16integration in Lithuanian women withcervical neoplasia. J. Cent. Eur.[J] Med..6(2).2011.205-212.
[207] Huang L.W,Chao S.L., Lee B.H. Integration of human papillomavirus type-16and type-18is a very early event in cervical carcinogenesis.[J] ofClin Pathol.,2008,61,627-31
[208] Collins S.I.,Williams C.C.,Wen K.,Young L.S., Roberts S., Murray P.G., et.al. Disruption of the E2Gene Is a Common and Early Event in the Natural Historyof Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study,[J]Cancer Res,2009,69:(9),3828-32
[209] Longworth M.S.,Laimins L.A. Pathogenesis of human papillomaviruses indifferentiating epithelium.[J] Microbiol Mol Biol Rev.,2004,68(2),362–72。
[210] Cheung J.L.K.,Keith W.K.L.,Cheung T.H.,Tang J.W.,Chan P.K.S. Viral load,E2gene disruption status, and lineage of human papillomavirus type16infectionin cervical neoplasia.[J] of Infect Dis.,2006,194,1706–12。
[211] Wentaensen N,Vinokurova S,Magnus VKD. Systematic review of genomicintegration sites of human papilloma2virus genomes in epithelial dysplasia andinvasive cancer of the female lower genital tract[J]. Cancer Research,2004,64(6):387823884.
[212] Ga lle A.V. Boulet,1Ina H. Benoy,2Christophe E. Human Papillomavirus16Loadand E2/E6Ratio inHPV16-Positive Women: Biomarkers for CervicalIntraepithelialNeoplasia≥2in a Liquid-BasedCytology Setting?.October27,2009; DOI:10.1158/1055-9965.
[213] Bosch, F. X., M. M. Manos, N. Munoz, M. Sherman, A. M. Jansen, J. Peto, M. H.Schiffman, V. Moreno, R. Kurman, K. V. Shah, et al.1995. Prevalence of humanpapillomavirus in cervical cancer: a worldwide perspective.[J].Natl. CancerInst.87:796-802.
[214] Andersson, S., H. Safari, M. Mints,I. Lewensohn-Fuchs, U. Gyllensten, and B.Johansson.2005. Type distribution, viral load and integration status of high-riskhuman papillomaviruses in pre-stages of cervical cancer (CIN). Br.[J].Cancer92:2195-2200.
[215] Arias-Pulido,H., C. L. Peyton, N. E. Joste, H. Vargas, and C. M. Wheeler.2006.Human papillomavirus type16integration in cervical carcinoma in situ and ininvasive cervical cancer.[J]. Clin. Microbiol.44:1755-1762.
[216] Briolat, J., V. Dalstein, M. Saunier, K. Joseph, S. Caudroy, J. L. Pretet, P.Birembaut, and C. Clavel.2007. HPV prevalence, viral load and physical state ofHPV-16in cervical smears of patients with different grades of CIN. Int.[J].Cancer121:2198-2204.
[217] Cheung, J. L., K. W. Lo, T. H. Cheung, J. W. Tang, and P. K. Chan.2006.Viral load,E2gene disruption status, and lineage of human papillomavirus type16infection incervical neoplasia.[J]. Infect. Dis.194:1706-1712.
[218] Cricca, M., A. M. Morselli-Labate, S. Venturoli, S. Ambretti, G. A. Gentilomi, G.Gallinella, S. Costa, M. Musiani, and M. Zerbini.2007. Viral DNA load, physicalstatus and E2/E6ratio as markers to grade HPV16positive women for high-gradecervical lesions. Gynecol. Oncol.106:549-557.
[219] De Marco, L., A. Gillio-Tos, L. Bonello, V. Ghisetti, G. Ronco, and F.Merletti.2007. Detection of human papillomavirus type16integration inpre-neoplastic cervical lesions and confirmation by DIPS-PCR and sequencing.[J].Clin. Virol.38:7-13.
[220] Fujii, T., N. Masumoto, M. Saito, N. Hirao, S. Niimi, M. Mukai, A. Ono, S. Hayashi,K. Kubushiro, E. Sakai, K. Tsukazaki, and S. Nozawa.2005. Comparison betweenin situ hybridization and real-time PCR technique as a means of detecting theintegrated form of human papillomavirus16in cervical neoplasia. Diagn. Mol.Pathol.14:103-108.
[221] Guo, M., N. Sneige, E. G. Silva, Y. J. Jan, D. E. Cogdell, E. Lin, R. Luthra, and W.Zhang.2007. Distribution and viral load of eight oncogenic types of humanpapillomavirus (HPV) and HPV16integration status in cervical intraepithelialneoplasia and carcinoma. Mod. Pathol.20:256-266.
[222] Kulmala, S. M., S. M. Syrjanen, U. B. Gyllensten, I. P. Shabalova, N. Petrovichev,P. Tosi, K. J. Syrjanen, and B. C. Johansson.2006. Early integration of high copyHPV16detectable in women with normal and low grade cervical cytology andhistology.[J]. Clin. Pathol.59:513-517.
[223] Tonon, S. A., M. A. Picconi, P. D. Bos, J. B. Zinovich, J. Galuppo, L. V. Alonio,and A. R. Teyssie.2001. Physical status of the E2human papilloma virus16viralgene in cervical preneoplastic and neoplastic lesions. J. Clin. Virol.21:129-134.
[224] Kulmala S.M.A., Syrj nen S.M., Gyllensten U.B.,Shabalova I.P.,Petrovichev N., Tosi P. et. al. Early integration of high copy HPV16detectable in women with normal and low grade cervical cytology and histology,[J] Clin Pathol.,2006,59(5),513–517
[225]郑莹,彭芝兰,楼江燕,王和，宫颈癌及癌前病变HPV-16存在状态检测的研究[J],中国肿瘤临床,2006,33(17):961-964.
[226] Mae¨lle Saunier,Sylvain Monnier-Benoit,Fre′de′ric Mauny,et al.Analysis of HumanPapillomavirus Type16(HPV16) DNA Load and Physical State for Identification ofHPV16-Infected Women with High-Grade Lesions or CervicalCarcinoma.[J]JOURNAL OF CLINICAL MICROBIOLOGY, Nov.2008,p.3678–3685.
[227] Huang LW,Choa SL,Lee BH.Integration of human papillomavirustype-16andtype-18is a very early event in cervical carcinogenesis,[J] Clin Pathol2008;61:627-31.
[228] Peitsaro P, Johansson B, Syrjanen S. Integrated human papillomavirustype16isfrequently found in cervical cancer precursors as demon-strated by a novelquantitative real-time PCR technique.[J] Clin Micro-biol2002;40:886–91.
[229] Briolat J,Dalstein V, Saunier M, et al. HPV prevalence, viral load and physical stateof HPV-16in cervical smears of patients with differentgrades of CIN. Int J Cancer2007;121:2198–204.32. Cricca M, Morselli-Labate AM, Venturoli S, et al. ViralDNA load,physical status and E2/E6ratio as markers to grade HPV16posi-tivewomen for high-grade cervical lesions. Gynecol Oncol2007;106:549–57.
[230] De Marco L, Gillio-Tos A, Bonello L, Ghisetti V, Ronco G, Merletti F.Detection ofhuman papillomavirus type16integration in pre-neoplastic cervical lesions andconfirmation by DIPS-PCR and se-quencing.[J] Clin Virol2007;38:7–13.
[231] Andersson S, Safari H, Mints M, Lewensohn-Fuchs I, Gyllensten U,Johansson B.Type distribution, viral load and integration state ofhigh-risk humanpapillomaviruses in pre-stages of cervical cancer(CIN).Br J Cancer2005;92:2195–200.
[232] Gallo G, Bibbo M,Bagella L, et al. Study of viral integration of HPV-16in youngpatients with LSIL.[J] Clin Pathol2003;56:532–6.
[233] Bauknecht T,Jundt F, Herr I,et al.A switch region determines the celltype-specificpositive or negative action of YY1on the activity of thehuman papillomavirus type18promotor.[J] Virol1995;69:1–12.
[234] Jundt F,Herr I,Angel P,Zur Hausen H, Bauknecht T. Transcriptionalcontrol ofhuman papillomavirus type18oncogene expression in dif-ferent cell lines: role oftranscription factor YY1.[J]Virus Genes1995;11:53–8.
[235] Bhattacharjee B, Sengupta S. CpG methylation of HPV16LCR at E2binding siteproximal to P97is associated with cervical cancer in pres-ence of intact E2.Virology2006;354:280–5.
[236] Arias-PulidoH,Peyton CL,JosteNE,et a.lHuman papillo-mavirus type16integrationin cervical carcinoma in situand in invasive cervical cancer[J].Clin Microbio,l2006,44:1755-1762.
[237]张帅,蔡红兵,丁晓华。HPV16E2基因各区域缺失与宫颈病变相关性的研究.[J]现代妇产科进展2010年10月第19卷第10期.
[238] Mingjun Jiang,Janet G.Baseman, Laura A.Koutsky, Qinghua Feng,ConstanceMao, Nancy B.Kiviat,and Long Fu Xi.Sequence Variation of HumanPapillomavirus Type16and Measurement of Viral Integration by Quantitative PCR.[J]. J Clin Microbiol.2009March;47(3):521–526.
[239] J. Peto, C.Gilham, O.Fletcher and F.E. Matthews, Thecervical cancer epidemic thatscreening has prevented in theUK.[J] Lancet364(2004),249–256.
[240]时艳梅,叶红,肖长义,等,宫颈病变患者病变组织HPV整合状态的变化及意义[J],山东医药,2009年,第49第6期.
[1] Doorbar J. Molecular biology of human papillomavirus infectionand cervical cancer[J].Clin Sci (Lond),2006,110(5):525-541.
[2] Lukaszuk K, Liss J, Woznia I,et al. Human papillomavirus type16status in cervicalcarcinoma cell DNA assayed by multiplex PCR[J].Journal of ClinicalMicrobiology,2003,41(2):608-612.
[3]徐海燕,辛晓燕.人乳头瘤病毒感染与宫颈癌的研究进展［J］.中国妇幼健康研究，2007，18(5):436-440.
[4]宋国兴.子宫颈癌致病因子人乳头瘤病毒的发现［J］.科技导报,2008,26(24):31-36.
[5] Bousarghin L, Hubert P, Franzen E,et al. Human papillomavirus16virus-like particlesuse heparan sulfates to bind dendritic cellsand colocalize with langerin in Langerhanscells[J]. J Gen Virol,2005,86(5):1297-1305.
[6] Giroglou T, Florin L, Schafer F, et al. Human Papillomavirus In-fection Requires CellSurface Heparan Sulfate[J]. J Virol,2001,75(3):1565-1570.
[7] Yoon C S, Kim K D A,Park S N, et al. alpha(6) Integrin is themain receptor of humanpapillomavirus type16VLP.Biochem Bio-phys Res Commun[J].2001,283(3):668-673.
[8] Evander M, Frazer I H, Payne E, et al. Identification of the al-pha6integrin as acandidate receptor for papillomaviruses[J]. JVirol,1997,71(3):2449-2456.
[9] Smith J L, Campos S K, Ozbun M A. Human papillomavirus type31uses a caveolin-1and dynamin-2mediated entry pathway forinfection of human keratinocytes[J]. JVirol,2007,81(18):9922-9931.
[10] Pelkmans L, Kartenbeck J, Helenius A.Caveolar endocytosis ofsimian virus40reveals a new two-step vesicular-transport path-way to the ER [J]. Nat Cell Biol,2001,3(5):473-483.
[11]Henrik Griesser,Heinz Sander, Cindy Walczak, et al. HPV Vaccine Protein L1PredictsDisease Outcome of High-Risk HPV+Early Squamous Dysplastic Lesions.Am J ClinPathol[J]. Nat Cell Biol,2009,132:840-845.
[12] Middleton K,Peh W, Southern S A, et al.Organisation of the hu-man papillomavirusproductive cycle during neoplastic progressionprovides a basis for the selection ofdiagnostic markers[J]. J Virol,2003,77(19):10186-10201.
[13] Hopman A, Smedts F, Dignef W, et al. Transition of high-gradecervical intraepithelialneoplasia to micro-invasive carcinoma ischaracterized by integration of HPV16/18and numerical chromo-some abnormalities[J]. J Pathol,2004,202:23-33.
[14][Klaes R,Friedrich T,Spikovsky D.et a1.Overexpression ofpl61NK4a as a specificmarker fordysplastic and neoplastic ep—ithelial cells of the cervic uteri[J].Int JCancer,2001,92(2)：276-284.
[15] Kim NR,Lin z,Kim KR,et a1.EpsteimBarr virus and P161”“4methylationinsquamouscell carcinoma andprecancerous lesions ofthe cervix uteri[J]J KoreanMed Sci,005．20(4)：636-642．
[16] KalofAN,CooperK.P161NK4a immunoexpression：surrogatemarker of high-risk HPVand high-grade cervical intraepithelialneoplasia[J] Adv Anat Pathol,2006,13(4)：190-194．
[17] Von Knebel-Doeh(，ritz M New marks for cervical dysplasia to vis—ualizethegeoonucchaos created by aberrant oncogenic papilloma—virus infections[J]．Eur JCanee.2002,38：2229-2242.
[18] Volgareva G,Zavalishina L,Andreeva Y.et a1.Protein p16as amarkerofdysplasticandneoplasticalterations in cervical epithelialcells[J]BMCCancer,2004,4(I)：58-65.
[19] Davidson EJ,Morris LS,Scott IS,et al.Minichromosomemaintenance(Mcm)proteins,cyclin B1and D1,phospho-histone H3and in situ DNA replication forfunctional a-nalysis of vulval intraepithelial neoplasia［J］Br J Canc-er,2003,88(2):257-262.
[20] Gupta N,Srinivasan R,Rajwanshi A. Functional biomarkers in cervical precancer：Anoverview［JDiagn Cytopathol,2010,38（8）：618~623.
[21] Mulvany NJ,Allen DG,Wilson SM. Diagnostic utility of p16INK4a: a reappraisal of itsuse in cervical biopsies ［J］. Pathology，2008，40（4）：335～344.
[22] Tsoumpou I,Arbyn M,Kyrgiou M,et al. p16（INK4a) immunostainingin cytologicaland histological specimens from the uterine cervix: asystematic review andmeta-analysis.Cancer［J］.Treat Rev,2009,35（3）：210～220.
[23]黄惠英,钱德英,岑坚敏.免疫组化P16蛋白在不同级别宫颈病变中表达差异的研究［J］.现代医院,2008,8（3）：14～15.
[24] O'Neill CJ,McCluggage WG.p16expression in the female genitaltract and its value indiagnosi［J］. Adv Anat Pathol,2006,13（1）：8～15.
[25] Sung CO,Kim SR,Oh YL,et al.The use of p16（INK4A）immunocytochemistry in"Atypical squamous cells which cannotexclude HSIL" compared with "Atypicalsquamous cells ofundetermined significance" in liquid-based cervical smears［J］Diagn Cytopathol,2010,38（3）：168～171.
[26] Focchi GR,Silva ID,Nogueira-de-Souza NC,et al.Immunohistochemical expressionof p16（INK4A） in normal uterine cervix，nonneoplastic epithelial lesions， andlow-grade squamousintraepithelial lesions［J］. Low Genit Tract Dis,2007,11（2）：98～104.
[27] Yildiz IZ,Usubutun A,FiratP, et a.l Efficiency of immu-nohistochemical p16expression andHPV typing in cervi-cal squamous intraepithelial lesion grading andreview ofthe p16literature[J]. PatholRes Prac Vo,l2007,203:445-449.
[28] Negri G, Egarter-Vigl E, KasalA, et a.l p16INK4a is ausefulmarker for the diagnosisof adenocarcinoma of thecervix uteri and its precursors: animmunohistochemicalstudywith immunocyto-chemical correlations[J]. Am JSurgPatho,l2003,27:187-193
[29] ON' eill CJ,McCluggageWG. p16expression in the fe-male genital tract and its valuein diagnosis[J]. AdvAnatPatho,l2006,13:1-8
[30] HilfrichR,Hariri J. Prognostic relevance ofhuman papil-lomavirus L1capsid proteindetection within mild andmoderate dysplastic lesions of the cervix uteri incombi-nation with p16biomarker[J].AnalQuantCytolHisto,l2008,30:78-82.
[31] Yoshida T, Sano T,Kanuma T, et a.l Immunochemical a-nalysis ofHPV L1capsidprotein and p16protein in liq-uid-based cytology samples from uterine cervicallesions [J].Cancer,2008,11:83-88
[32] Yu R, HeaneyAP, LuW, et a,l Pi tui tary tumor t rahs forming genecauses aneuploidyand p53-dependent and p53-independent apoptosis[J].J BiolChem,2000,275:36502-36505.
[33]靳玉兰,张伟,刘伯齐,等.食管癌前病变及原位癌组织中Ki67、p53、iNOS的异常表达[J].中华肿瘤杂志,2001,23(2):129-131.
[34] Salvesen HB,Iversen0E,Akslen L A.Prognostic significance of an-giogenesis andKi67,P53,and P21expression：a population based endometrial carcinoma study[J]．JChin0ncol,1999,17：1382.
[35]李东辉,李明众.张薛榜．口一catenin和ki-67在人宫颈癌组织中的表达及其意义[J].实用癌症杂志.2007,22(1)：28-30．
[36] GAOP.ZH()U GY.Y1N G,et aI.Lymphatic vessel density asa prognostic indicator forpatients with stage I cervicalcarcinoma[J].Human Pathology．2006．37(6)：719-725.
[37] Van de PUTTE G,KRlsTENsEN GB,LIE AK,et a1.CycIinsand proliferation markersin early squamous cervicalcarcinorna[J]Gynecologic(hcoIogy，2004，92(1)：40-46．2.3.
[38] Shroyer KR,Homer P, Heinz D, et al. Validation of a novel immunocytochemicalassay for topoisomerase II-a and minichromosome maintenance protein2expressionin cervical cytology.[J]Cancer2006;108:324–330.
[39] Kelly D,Kincaid E, Fansler Z, et al. Detection of cervical high-grade squamousintraepithelial lesions from cytologic samples using a novel immunocytochemicalassay (ProEx C). Cancer2006;108:494–500.
[40] Badr RE,Walts AE, Chung F, et al. BD ProExC: a sensitive and specific marker ofHPV-associated squamous lesions of the cervix. Am J Surg Pathol2008;32:899–906.
[41] Chan KY, Walts AE, Bose S. ProExC is a marker for HPV-associated anal lesions.[J]Mod Pathol2007;20(Suppl2):109A.
[42]张桂香,赵学东,赵卫平.MCM2蛋白在肿瘤中的表达及意义［J］.现代肿瘤医学,2008，16(12):2210-2212
[43] Badr RE,Waltes AE,Chung F,et al.BD ProEx C: A Sen-sitive and specific marker ofHPV-associated squamous le-sions of the cervix［J］Am J Surg Path.2008,32(6):899-906.
[44] Mukherjee G,Muralidhar B,Bafna UD,et al.Mcm immu-nocytochemistry as a first linecervical screening test indeveloping countries: a prospective cohort study in are-gional cancer centre in India［J］．Br J Cancer,2007,96(7),1107-1111.
[45] Shroyer KR,Homer P,Heinz D,et al, Validationofa novelimmunocytochemical assayfor topoisomerase Ⅱ-alphaand minichromosome maintenance protein2expressionincervical cytology［J］Cancer,2006,108(5):324-330.
[46] Aximu D,Azad A,Ni R,et al.A pilot evaluation of a no-vel immunohistochemicalassay for topoisomerase Ⅱ-al-pha and minichromosome maintenance protein2expres-sion(ProEx C) in cervical adenocarcinoma in situ，adeno-carcinoma，andbenign glandular mimics［J］Int J Gyne-col Pathol,2009,28(2):114-119.
[47] Mukherjee G,Freeman A,Moore R,et al.Biologic factorsand response to radiotherapyin carcinoma of the cervix［J］.Int J Gynecol Cancer,2001,11(3):187-193.
[48] Kato K,Toki T,Shimizu M,et al.Expression of replica-tion-licensing factors MCM2and MCM3in normal,hy-perplastic,and carcinomatous endometrium: correlationwithexpression of Ki-67and estrogen and progesteronereceptors［J］. Int J GynecolPathol,2003,22(4):334-340.
[49] Kulkarni AA,Loddo M,Leo E,et al.DNA replication li-censing factors and aurorakinases are linked to aneu-ploidy and clinical outcome in epithelial ovariancarcino-ma［J］.Clin Cancer Res,2007,13(20):6153-6161.
[50] Gakiopoulou H,Korkolopoulou P,Levidou G,et al.Mini-chromosome maintenanceproteins2and5in non-benignepithelial ovarian tumours: relationship with cellcycleregulators and prognostic implications［J］.Br J Cancer,2007,97(8):1124-1134.
[2] Arbyn, X. Castellsague, S. de Sanjose.Worldwide burden of cervical cancer in2008.[J]Annals of Oncology.22:2675–2686,2011.
[3]马松,安琳.1996-2005年中国女性宫颈癌死亡水平研究.现代预防医学.2009；36（1）：47-50.
[4]姜淑清,土送爱,周俊兰,等.新疆策勒县妇女病现状调查与分析[J].中国妇幼保健,2006,21(4):524-526.
[5]拉莱苏祖克,彭玉华,周康,房新志,王丽.新疆不同民族子宫颈癌发病趋势分析[J].新疆医科大学学报.2006；29(7)：569-571.
[6]张国庆,刘开江,赖小军,等.新医大附属肿瘤医院1989~2002年住院病人恶性肿瘤分布[J].新疆医科大学学报,2003,26(4)：393-394.
[7] Zur Hausen H，de Villiers EM，Gissmann L.Papilloma-virus infections and humangenital cancer［J］.GynecolOncol，1981,12: S124-128．
[8] Zur Hausen H．Immortalization of human cells and theirmalignant conversion by highrisk human papillomavirus genotypes In;1999: Elsevier;1999:405-411．
[9] deVilliersEM, auquetC, BrokerTR, et a.l Classification ofpapillomaviruses[J]. Virology,2004,324(1):17-27·
[10]Doorbar J.Molecular biology of human papillomavirus in fection and cervical cancer[J]. Clinical Science (2006)110,(525–541).
[11]Bouvard V, Baan R, Straif K, Grosse Y, Secretan B,El Ghissassi F, et al. A review ofhuman carcinogens-PartB: biological agents. Lancet Oncol.2009;10:321-2.
[12]MufiozN, BoschFX, des Setal.International Agency for search on CanCerMultieenter Cervieal Cancer Study Group.EP idemiologie N Eng [J] Med.2003;348:518一527.
[13]Clifford GM,Smith JS,Plummer M etal.Human Papillomavirus typ esininvasiveeerviea leaner world wide meta analysis.Br [J] Caneer2003:88:63一73.
[14]ZhaoY,LinH,ShenDetal.Distribution of HPV genotype esinuter in ervical lesions inYanbian,northern China.Pathol Int.2008;58:643一7
[15]HongD,YeF,ChenH,etal. Distribution of human Papillomavirus genotype esin thePatients with eerviea lear cinomaandits Precursorsin Zhejiang Province,China.Int [J]Gyneeol Caneer.2008.18:104一109.
[16]G M Clifford SG，R Herrero,N Muoz,P J F Snijders,and the IARC HPV PrevalenceSurveys Study Group.Worldwide distribution of humanpapillomavirus types incytologically normal women in the International Agency for Research on CancerHPV preva-lence surveys: a pooled analysis［J］．Lancet，2005．
[17]玛依努尔·尼牙孜,李丽,陈凤,章文华,朱开春,刘新伟,热孜亚·买买提孜,孙振柱,赵丽霞,张询,潘秦镜,刘新伏,武艳萍,乔友林.新疆维吾尔族女性人乳头瘤病毒感染与宫颈癌相关性的流行病学调查［J］.临床肿瘤学杂志2011年4月第16卷第4期。
[18]李霓,代敏.中国妇女人乳头瘤状病毒感染的多中心横断面研究.[J]中华疾病控制杂志.2008；12（5）：411-415.
[19]陈凤,曾转萍,刘彬,黄曼妮,张洵,潘秦镜,章文华,赵芳辉,戎寿德,乔友林.山西省阳城县妇女人乳头瘤病毒感染的危险因素分析.[J]实用肿瘤杂志.2004；19(4):349-351.
[20]Wen Chen, Xun Zhang, Anco Molijn, Mayinuer Niyazi et al. Human papillomavirustype-distribution in cervical cancerin China: the importance of HPV16and18[J].Cancer Causes Control (2009)20:1705–1713
[21]Clifford GM, Gallus S, Herrero R, et al. Worldwide distribution ofhumanpapillomavirus types in cytologically normal women in the In-ternational Agency forResearch on Cancer HPV prevalence surveys:a pooled analysis [J]. Lancet,2005,366(9490):991-998.
[22]鲍彦平,李霓,王鹤等.中国妇女子宫颈乳头瘤病毒型别分布的Meta分析[J].中华流行病学杂志，2007，28，（10）：6.
[23]de Sanjose S,Quint WG, Alemany L, et al. Human papillomavirus genotype attributionin invasive cervical cancer: a retrospective cross-sectional worldwide study.[J]Lancet Oncol.2010;11:1048-1056.
[24]Guzhalinuer ABLZ,Cheng JX. The spectrum of HPV infection inXinjiang Uighurwomen with cerv ica l cancer [J]. Tumor,2007,27(5):379-382(In Chinese).
[25]Cates, W., Jr.1999. Estimates of the incidence and prevalence of sexually transmitteddiseases in the United States[J]. Sex Transm. Dis.26(4Suppl.):S2–S7.
[26]RuudL,M.Bkkers.Epidemiological and clinical aspects of human papillomavirusdetection in the preverition of cervical cancer [J].Rev Med Virol2004，14:95一105.
[27]黄志红,钱德英,王丁等.人乳头状瘤病毒负荷量与宫颈癌以及宫颈癌前病变的相关研究[J].中国妇幼保健，2006，21(11):1557-1559
[28]Zheng ZM,Baker CC.Papillomavirus genome structure,expression,andpost-transcriptional regulation.[J]Front Biosci.2006;11:2286-302.
[29]OsterAG.Natural history of cervical intraepithelial neoplasia: a critical review[J].Int JGynecol Pathol,1993,12(2):186
[30]Moscicki AB, Schiffman M, Kjaer S, et al. Chapter5:Updating the natural history ofHPV and anogenital cancer.[J] Vaccine2006;24(Suppl3):42-51.
[31]Peto, C. Gilham, O. Fletcher and F.E. Matthews, Thecervical cancer epidemic thatscreening has prevented in the UK,[J] Lancet364(2004),249–256.
[32]Baak JP, Kruse AJ,Janssen E,van Diermen B. Predictive testing ofearly CINbehaviour by molecular biomarkers.[J] Cell Oncol2005;27:277–80
[33]Wright TC Jr, Schiffman M. Adding a test for human papillomavirus DNA tocervical-cancer screening. N Engl [J] Med.2003;348:489-490.
[34]Schiffman M, Castle PE, Jeronimo J, et al. Human papillomavirus and cervical cancer.[J] Lancet.2007;370:890-907.
[35]Saslow D, Solomon D, Lawson HW,et al:American Cancer Society, American Societyfor Colposcopy and Cervical Pathology, and American So-ciety for ClinicalPathology screening guidelines forthe prevention and early detection of cervicalcancer.[J]CA Cancer Clin62:147-172,2012.
[36]Saslow D, Solomon D, Lawson HW, et al:American Cancer Society, AmericanSociety for Col-poscopy and Cervical Pathology, and American Soci-ety for ClinicalPathology Screening Guidelines for theprevention and early detection of cervicalcancer.[J]Low Genit Tract Dis [epub ahead of print onMarch13,2012].
[37]Mayrand MH, Duarte-Franco E,Rodrigues I,et al: Human papillomavirus DNA versusPapanico-laou screening tests for cervical cancer.[J]N EnglMed357:1579-1588,2007.
[38]Bulkmans NW, Berkhof J, Rozendaal L, etal: Human papillomavirus DNA testing forthe detection of cervical intraepithelial neoplasia grade3and cancer:5-yearfollow-up of a ran-domised controlled implementation trial.[J] Lancet370:1764-1772,2007.
[39]Naucler P, Ryd W, To¨ rnberg S, et al: Humanpapillomavirus and Papanicolaou teststo screenfor cervical cancer. N Engl J Med357:1589-1597,2007
[40]Ronco G, Giorgi-Rossi P, Carozzi F, et al:Efficacy of human papillomavirus testing forthedetection of invasive cervical cancers and cervicalintraepithelial neoplasia: Arandomised controlledtrial.[J]Lancet Oncol11:249-257,2010.
[41]Anttila A, Kotaniemi-Talonen L, Leinonen M,et al: Rate of cervical cancer, severeintraepithelial neoplasia, and adenocarcinoma in situ in primaryHPV DNA screeningwith cytology triage: Ran-domised study within organised screening pro-gramme.BMJ340:c1804,2010.
[42]Cuzick J, Clavel C, Petry KU, et al: Overviewof the European and North Americanstudies on HPVtesting in primary cervical cancer screening.[J] Int Cancer119:1095-1101,2006.
[43]Ronco G, Giorgi-Rossi P, Carozzi F, et al:Results at recruitment from a randomizedcontrolledtrial comparing human papillomavirus testing alonewith conventionalcytology as the primary cervicalcancer screening test.[J]Natl Cancer Inst100:492-501,2008.
[44]Sankaranarayanan R, Nene BM, Shastri SS, etal: HPV screening for cervical cancer inrural India.[j]N Engl Med360:1385-1394,2009.
[45]Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human papillomavirustesting, and risk for cervical neoplasia: a10-year cohort analysis.[J] Natl Cancer Inst.2003;95:46-52.
[46]Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology andhuman papillomavirus testing in cervical cancer screening: joint European cohortstudy. BMJ.2008;337:a1754.
[47]Schiffman M, Glass AG, Wentzensen N, et al. A long-term prospective study oftype-specific human papillomavirus infection and risk of cervical neoplasia among20,000women in the Portland Kaiser Cohort Study.[J] Cancer EpidemiolBiomarkers Prev.2011;20:1398-1409.
[48]Raquel Ibá ez, Judit Moreno-Crespi, Montserrat Sardà, et al. Prediction of cervicalintraepithelial neoplasia grade2+(CIN2+) using HPV DNA testing after adiagnosisof atypical squamous cell of undeterminedsignificance (ASC-US) inCatalonia, Spain ［J］BMC Infectious Diseases2012,12:25.
[49]Song H, Moseley PL, Lowe SL, et al. Inducible heat shock protein70enhancesHPV31viral genome replication and virion production during the differentiation-dependent life cycle in human keratinocytes［J］. Virus Res,2010,147（1）:113-122.
[50]Gagnon D,Joubert S, Sénéchal H, et al. Proteasomal degradation ofthe papillomavirusE2protein is inhibited by overexpression of bro-modomain-containing protein4［J］J Virol,2009,83（9）:4127-4139.
[51]Lurchachaiwong W,Junyangdikul P,Termrungruanglert W,et al.Whole genomesequence analysis of human papillomavirus type18from infected Thai women ［J］Clin Pathol.2010,53（3）:161-166.
[52]Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53and Gene ExpressionProfiling. Buitrago-Perez A, Garaulet G, Vazquez-Carballo A, Paramio JM, andGarcia-Escudero R. Curr Genomics, Mar ［J］Clin Pathol2009;10(1):26-34.
[53]Mark H. Stoler, Thomas C. Wright Jr, Abha Sharma,,et al. High-Risk HumanPapillomavirus Testing in Women With ASC-US CytologyResults From theATHENA HPV Study. Am [J] Clin Pathol2011;135:468-4757F
[54]Moberg M, Gustavsson I, Wilander E, et al. High viral loads of humanpapillomavirous predict risk of invasive cervical carcinoma [J]. Br J Cancer,2005,92(5):891-894.
[55]Samuel R, Francois C, Dan Fontaine, James B, Nicholas E, Prafull G, Veeresh G, GlenH, Elias B, Nick K, Christopher G, and Adrian L. Aptima HPV E6/E7mRNA Test Isas Sensitive as Hybrid Capture2Assay but More Specific at Detecting CervicalPrecancer and Cancer.[J] Clin Microbiol.2011;49(2):557-564.
[56]Jonathan H, Abul E, Erin S, Domenico Co, Bridgett R, and David S. HPV L1CapsidProtein Detection and Progression of Anal Squamous Neoplasia.Am [J] Clin Pathol,2011;135(5):436-441.
[57]Stuart IC, Christothea CW, Kaisheng W, Lawrence S. Young, Sally R, Paul G. Murray,and Ciaran B.J. Disruption of the E2Gene Is a Common and Early Event in theNatural History of Cervical Human Papillomavirus Infection: A Longitudinal CohortStudy.[J]Cancer Res. May2009;69:3828-3832.
[58]Ga lle AVB,Ina HB, Christophe ED, Caroline AJH, Marc A, Niel H, Annie JV, andJohannes JB.Human Papillomavirus16Load and E2/E6Ratio in HPV16-PositiveWomen: Biomarkers for Cervical Intraepithelial Neoplasia2in a Liquid-BasedCytology Setting.[J]Cancer Epidemiol. Biomarkers Prev. Nov2009;18:2992-2999.
[59]Brooke C, Nicole B, and Scott BVP.Human Papillomavirus E6Regulates theCytoskeleton Dynamics of Keratinocytes through Targeted Degradation of p53.[J]Virol. Nov2007;81:12675-12679.
[60]Kate C and Nicolas W.Human Papillomavirus mRNA and p16Detection asBiomarkers for the Improved Diagnosis of Cervical Neoplasia. Cancer Epidemiol.[J]Biomarkers Prev. Oct2008;17:2536-2545.
[61]Dimitrios H, George AP, George DV, Alexandros R, Sonia M, Zannis V, Emmanuel D,and Aris A. p16INK4A Is a Strong Biomarker for Cervical Intraepithelial Neoplasiaand Invasive Cervical Carcinoma: A Reappraisal.[J]Reproductive Sciences, Jul2009;16:685–693
[62]J de Wilde, SM Wilting, CJ Meijer, MA van de Wiel, B Ylstra, PJ Snijders, and RDSteenbergen. Gene expression profiling to identify markers associated withderegulated hTERT in HPV-transformed keratinocytes and cervical cancer. Int [J]Cancer, Feb2008;122(4):877-888.
[63]李慧弘,肖长义. HPV DNA整合,E2破坏,HPV E2/E6比值与宫颈癌关系的研究.[J]中国免疫学杂志,2010；26（7）：670-673.
[64]时艳梅,叶红,肖长义,陈建玲,王雅琴,吴江峰.宫颈病变患者病变组织HPV整合状态的变化及意义.[J]山东医药.2009；（49）6：1-3.
[65]肖巍,卞美璐,马莉,刘军,陈颖.子宫颈液基细胞学检查异常的涂片中人乳头状瘤病毒L1蛋白的表达及其意义.[J]中华妇产科杂志.2009,44（12）：887-891.
[66]Ordonez RM, Espinosa AM, Sanchez–Gonzalez DJ et al. Enhanced oncogenicity ofAsian-American human papillomavirus16is associated with impaired E2repressionof E6/E7oncogene transcription.[J]Gen Virol,2004；85(6):1433-1444
[67]PettM, Coleman N. Integration of high-risk human papillomavir-us: a key event incervical carcinogenesis?[J]. J Patho,l2007,212(4):356-367.
[68]Vinokurova S, Wentzensen N, Kraus I, et a.l Type-dependent in-tegration frequencyofhuman papillomavirusgenomes in cervical le-sions[J].CancerRes,2008,68(1):307-313.
[69]WentzensenN, Vinokurova S, DoeberitzMV. Systematic review ofgenomic integrationsites of human papillomavirus genomes in epi-thelial dysplasia and invasive cancerof the female lower genitaltract[J]. CancerRes,2004,64(11):3878-3884.
[70]Henrik Griesser, Heinz Sander, Cindy Walczak, et al. HPV Vaccine Protein L1Predicts Disease Outcome of High-Risk HPV+Early Squamous DysplasticLesions.Am J Clin Pathol[J]. CancerRes2009,132:840-845.
[71] Castellsague X,Diaz M,de Sanjose S,et al. Worldwide human papillomavirus etiologyof cervical adenocarcinoma and its cofactors: implications for screening andprevention [J]. Natl Cancer Inst.2006Mar1;98(5):303-315
[72]李瑞珍,石菊芳,周庆芝等.应用基因芯片技术检测高危型人乳头瘤病毒在宫颈癌筛查中的评价[J].中华医学杂志,2006,86(5):307-311
[73]Kim KH,Yoon MS,Na YJ,et al.Development and evaluation of a highly sensitivehuman papillomavirus genotyping DNA chip[J].Gynecol Oncol.2006Jan；100(1):38-43
[74]Choi YD,JungWW,Nam JH,et al.Detection of HPV genotypes in cervical lesions bythe HPV DNA chip and sequencing[J].Gynecol Oncol,2005,98(3):369-375.
[75]李瑞珍,石菊芳,周庆芝等.应用基因芯片技术检测高危型人乳头瘤病毒在宫颈癌筛查中的评价[J]巾华医学杂志,2006,86(5):307-311
[76] Kim KH,Yoon MS,Na YJ,et al. Development and evaluation of a highly sensitivehuman papillomavirus genotyping DNA chip [J].ynecol Oncol.2006Jan;100(1):38-43
[77] Choi YD,JungWW,Nam JH,et al. Detection of HPV genotypes in cervical lesions bythe HPV DNA chip and sequencing[J]. Gynecol Oncol,2005,98(3):369-375
[78] Masumoto N, Fujii T, Ishikawa M, et al·Dominant humanpapillomavirus16infectionin cervical neoplasia in young Japanesewomen; study of881outpatients·[J]GynecolOnco,l2004,94:509-514·
[79] Stanczuk GA, Kay P, Sibanda E,et al·Typing of humanpapillomavirus in Zimbabweanpatients with invasive cancer of theuterine cervix·[J]ActaObstet Gynecol Scand,2003,82:762-766·
[80].Dalstein V, Riethmuller D, Pretet J L,et al.·Persistence and load of high-risk HPV arepredictors for development of high-grade cervical lesions: a longitudinal Frenchcohort study［J］.Int J Cancer,2003,106(3):396-403。
[81]乐杰,主编.妇产科学.第7版.北京:人民卫生出版社,2008.262-263
[82] Tavassoli F A,Devilee P. WHO classification of tumor. Pathology genetics of tumorsof the breast and female genital organs[M].Lyon: IARC Press,2003:262
[83] Cox J T. Human pap illomavirus testing in p rimary cervical screening and abnormalpapanicolaou management [J]. Obstet Gynecol Surv,2006,6191:15–25
[84]Clifford GM,Swith JS,PlummerM,eta.l Human papillomavius types in iuvasivecervica cancerworldwide:a weta-analysis [J]. Br J Cancer,2003,88:63-73.
[85]Smith JS,Lindsay L,HootsB et a.l Human papillomavirus type dis-tribution in invasivecervical cancer and high-grade cervical lesions: ameta-analysis updat[J]. Int JCancer,2007,121(3):621.
[86]BaoYP, LiN, Smith JS, et a.l Human papillomavirus type-distribu-tion in the cervix ofchinesewomen: ameta-analysis [J]. Int J STDA IDS,2008,19(2):106.
[87]Wheeler CM,Hunt WC,Joste NE, et al. Human papillomavirus geno-type distributions:implications for vaccination and cancer screening in the United States.[J] NatlCancer Inst.2009;101(7):475–487.
[88]CoglianoV,Baan R,StraifK,et a.l Carcinogenicity ofHuman papillo-mavius[J].LancetOnco,l2005,6(4):204.
[89] Harper DM,Franco EL,Wheeler CM,Moscicki AB,RomanowskiB,Roteli-Martins CM,Jenkins D,Schuind A,Costa Clemens SA,Dubin G. Sustained efficacy up to4–5yearsof a bivalent L1virus-like particle vaccine against human papillomavirus types16and18:follow-up from a randomised control trial.[J]Lancet2006;367:1247–55.
[90] Villa LL,Costa RL,Petta CA,Andrade RP,Ault KA,Giuliano AR,Wheeler CM,Koutsky LA,Malm C,Lehtinin M,Skjeldestad FE,Olsson SE,et al.Prophylacticquadrivalent human papilloma-virus (types6,11,16and18) L1virus-like particlevaccine in youngwomen: a randomised double-blind placebo-controlledmulticentrephase II efficacy trial.[J]Lancet Oncol2005;6:271–8.
[91] Anil K.Chaturvedi,Hormuzd A.Katki,Allan Hildesheim, Ana Cecilia Rodr!guez,Wim Quint,Mark Schiffman,Leen-Jan Van Doorn,Carolina Porras,Sholom Wacholder,Paula Gonzalez,Mark E.Sherman and Rolando Herrero for the CVT Groupb.HumanPapillomavirus Infection with MultipleTypes:Pattern of Coinfection and Risk ofCervical Disease.[J]ID2011:203
[92] Eiben GL,da Silva DM,Fausch SC,et al. Cervical cancer vaccines: recent advances inHPV research [J] Viral Immunol,2003,16(2):111-121
[93] Guzhalinuer ABLZ, Cheng JX. The spectrum of HPV infection inXinjiang Uighurwomen with cerv ica l cancer [J] Tumor,2007,27(5):379-382(In Chinese).
[94]张向楠,王英红,张文杰,李文婷,刘莹,张岚.新疆维吾尔族及汉族宫颈癌及高危癌前病变与HPV感染亚型关系研究.[J]中华实用诊断与治疗杂志2012年4月第26卷第4期.
[95]Susanne K. Kj r,Kirsten Frederiksen,Christian Munk,Thomas Iftner Long-termAbsolute Risk of Cervical Intraepithelial Neoplasia Grade3or Worse FollowingHuman Papillomavirus Infection: Role of Persistence.[j]. JNCI Vol.102, Issue19October6,2010.
[96] Clifford GM，Smith JS,Plummer M,et al． Human papil-lomavirus types in invasivecervical cancer worldwide: ameta－analysis[J] Br J Cancer,2003(1):63－73．
[97] Clifford GM,Smith JS,Plummer M,et al. Human papil-lomavirus types in invasivecervical cancer worldwide:ameta－analysis[J]Br J Cancer,2003(1):63－73.
[98]苏锡康,崔金环,杨光,等.宫颈癌组织中人乳头瘤病毒基因分型的研究［J］医学临床研究,2008(6):988－990.
[99]古扎丽努尔·阿不力孜,彭芝兰,刘珊玲等.HPV及其亚型在四川西北地区汉族及新疆南部地区维吾尔族妇女宫颈癌组织中的差异表达［J］中华微生物学和免疫学杂志,2004(5):408．
[100]古扎丽努尔·阿不力孜;帕提曼·米吉提;李庭芳;程静新;李华;路玲HPV各亚型在新疆各地区维吾尔族宫颈癌患者中的分布研究.[j].新疆医科大学学报.2009年第05期
[101]郑义,高丽敏,井明霞,张金丽,芮东升,王英红,阿曼古丽何玲赵娟杨磊.新疆维族妇女感染的HPV型别分布的研究.[J]现代生物医学进展Vol.12NO.1JAN.2012.
[102]杨英捷,赵健.2285例女性下生殖道人乳头状瘤病毒感染筛查结果分析[J]中国实用妇科与产科杂志,2006，(6):444－445.
[103]韩定英,吴洁,姜碧卿,等.深圳市罗湖区1420例妇女生殖道人乳头瘤病毒筛查结果分析[J]中国初级卫生保健,2008，22(2):42－43.
[104]靳琼,沈铿,李辉,等.西藏自治区妇女子宫颈人乳头状瘤病毒感染现状调查及相关因素分析[J].中华妇产科杂志，2009,44(12):898－902.
[105]胡庆兰,刘永珠,朱伟艳,唐霓,黄振勇,胡国洪.5000例宫颈细胞人乳头状瘤病毒感染筛查结果分析.[J]现代医院2012年2月第12卷第2期103-146.
[106] Clifford GM,Smith JS, PlummerM,et a.l Human papillomavirustypes in invasivecervical cancerworldwide: ameta-analysis[J]. Br Cancer,2003,88(1):63-73.
[107] Laia Bruni,Mireia Diaz,Xavier Castellsague′,Elena Ferrer,F. Xavier Bosch,andSilvia de Sanjose′Cervical Human Papillomavirus Prevalencein5Continents:Meta-Analysis of1Million Womenwith Normal Cytological Findings.[j]TheJournal of Infectious Diseases2010;202(12):1789–1799.
[108]李霓,张思维,陈万青,等.亚洲妇女宫颈癌中人乳头状瘤病毒型别分布的Meta分析[J].中国肿瘤,2010,(3):195-202.
[109] Kazunari Kondo, Asami Uenoyama, Ryo Kitagawa, Hajime Tsunoda, RikaKusumoto-Matsuo, Seiichiro Mori,2Yoshiyuki Ishii, Takamasa Takeuchi,Tadahito Kanda, and Iwao Kukimoto.Genotype Distribution of HumanPapillomaviruses in Japanese Women with Abnormal Cervical Cytology. OpenVirol [J]. Clinica Chimica Acta2012;6:277–283.
[110]Yong Shen, Jiao-Mei Gong,Yan-Qing Li, Yu-Mei Gong, Dong-Mei Lei, Guo-MeiCheng,Xiao-Fu Li.Epidemiology and genotype distribution of humanpapillomavirus (HPV) in women of Henan Province, China.[J]. Clinica ChimicaActa.Volume415,16January2013, Pages297–301.
[111]王又又,向群英,佘茜,谭云,等。宫颈癌高发区妇女HPV感染及影响因素分析。[J]中国公共卫生2011年3月第27卷第3期。
[112] Wheeler CM,Castellsague X, Garland SM,et al.Cross-protective efficacy ofHPV-16/18AS04-adjuvanted vaccine against cervical infection and precancercaused by non-vaccine oncogenic HPV types:4-year end-of-study analysis of therandomised, double-blind PATRICI Atrial.[J]Lancet Oncol.2012;13:100–110.
[113] Kovács K, Varnai AD, Bollmann M, et al. Prevalence and geno type distribution ofmultiple human papillomavirus infection in theuterine cervix: a7.5-yearlongitudinal study in a routine cytolo gy-based screening population in WestGermany[J]. J Med Virol,2008,80(10):1814-1823.
[114]陶萍萍,卞美璐,李敏,等.HPV多重感染与宫颈病变关系探讨[J]中国妇产科临床杂志2006年3月(7):94-96.
[115] Sowjanya AP,Jain M,Poli UR,et al.Prevalence and distribution of high-riskhumanpapilloma virus(HPV)types in invasive squamous cell carcinoma of thecervix andin normal women in Andhra Pradesh,India[J].BMC Infect Dis.2005Dec22；5:116
[116] Sanchez-Anguiano LF,Alvarado-Esquvel C,Reyes-Romero MA,et al.Humanpapillomavirus infections in women seeking cervical Papanicolaou cytology ofDurango,Mexico:prevalence and genotypes[J].BMC Infect Dis.2006Feb20；
[117] Ciotti M,Paba P,Bonifacio D,et al.Single or multiple HPV types in cervical cancerand associated metastases[J].Oncol Rep.2006Jan；15(1):143-148
[118] Lee SA,Kang D,Seo SS,et a.l Multiple HPV infection in cervicalcancer screenedbyHPV DNA chip[J].CancerLett,2003,198(2):
[119]王维鹏我院妇女宫颈感染高危型人乳头瘤病毒基因型分布[J].实用医学杂志,2007,23(13):2040-2041.
[120] Bao YP,Li N.Smith JS.et a1.Humanpapillomavirus type distribution in women fromAsia:a meta—analysis.[J] Gynecol Cancer,2008,18：7I-79.
[121]An HJ, Cho NH,Lee SY,et al. Correlationof cervical carcinoma andprecancerouslesions wit h human papilliomavirus (HPV) genotypes detected with the HPV DNA chip microar2ray met hod[J]. Cancer,2003,97(7):1672-1680.
[122] Munoz N,Bosch FX,Sanjose S D,et al. Epidemiologic classification of humanpapillomavirus types associated wit h cervical cancer[J].N Engl J Med,2003,348(6):518-527.
[123] Kay P,Soeters R,Nevin J,et al.High prevalence of HPV16in South African womenwit h cancer of t he cervix and cervical int raepit helial neoplasia[J]. MedVirol,2003,71(2):265-273
[124]吕虹,刘志忠,刘竞争,等.人乳头瘤病毒基因分型检测在绝经后妇女HPV感染中的应用价值[J].中国老年学杂志,2011,31(11):2117-2118.
[125] TANG Y, ZHANG J, FANG CY, et al. Correlation analysis ofcervical intraepithelialneoplasia and HR-HPV infection inmarried women in Fengtai District[J]. ChineseJournal of Womanand Child Health Research,2011,22(4):418-419,422. Chi-nese
[126] Moscicki AB,Shiboski S,Hills NK,et al.Regression oflow-grade squamousintra-epithelial lesions in young wom-en[J].Lancet,2004,364(6):1678-1683.
[127] Ferlay J,Parkin DM,Curado MP,et al. Cancer Incidence in Five Continents.[J]International Agency for Research on Cancer2010, I to IX, April,2011.128-135.
[128] Dufresne S,Sauthier P,Mayrand MH, et al. Human Papillomavirus (HPV) DNATriage of Women with Atypical Squamous Cells of Undetermined Significance withAmplicor HPV and Hybrid Capture2Assays for Detection of High-GradeLesions of the Uterine Cervix.[J] Clin Microbiol2011,49(1):48-53.
[129] Ostensson E,Fr berg M,Hjerpe A,et al. Economic analysis of human papillomavirustriage, repeat cytology, and immediate colposcopy in management of women withminor cytological abnormalities in Sweden.[J]Acta Obstet Gynecol Scand2010,89(10):1316-1325.
[130] Raquel Ibá ez, Judit Moreno-Crespi,Montserrat Sardà,et al. Prediction of cervicalintraepithelial neoplasia grade2+(CIN2+) using HPV DNA testing after adiagnosisof atypical squamous cell of undeterminedsignificance (ASC-US) inCatalonia, Spain [J]BMC Infectious Diseases2012,12:25.
[131] Mark H. Stoler,Thomas C.Wright Jr,Abha Sharma,et al.High-Risk HumanPapillomavirus Testing in Women With ASC-US CytologyResults From theATHENA HPV Study.[J] Am J Clin Pathol2011;135:468-475
[132] Roberto Flores1,Mary Papenfuss1,Walter T. Klimecki2,et al.Cross-sectional analysisof oncogenic HPV viral load and cervical intraepithelial neoplasia. Int.[J] Cancer:118,1187–1193(2006).
[133] Jarboe EA,Venkat P, Hirsch M S,et al. A Weakly Positive Human PapillomavirusHybrid Capture II Result Correlates With a Significantly Lower Risk of CervicalIntraepithelial Neoplasia2,3After Atypical Squamous Cells of UndeterminedSignificance.[J]Cytology Journal of Lower Genital Tract Disease: July2010-Volume14-Issue3-pp174-178
[134] M.origoni,G.carminati,M.sider,et al.“Low-grade positivity” of HPV viral load afteratypical Squamous cells of undetermined significance (ASCUS) cytology identifieswomen at low-risk for cervical intraepithelial neoplasia grade2and3.[J] Europeanjournal of gynaecological oncology:vol.XXXⅢ,no.3,2102.
[135] Attila T Lorincz,Philip E Castle,Mark E Sherman,et al.Viral load of humanpapillomavirus and risk of CIN3or cervical cancer.[J]lancet.Volume360,Issue9328,20July2002, p228–229
[136] Hilfrich R,Hariri J.Prognostic relevance of human papillomavirus L1capsid proteindetection within mild and moderate dysplastic lesions of the cervix uteri incombination with p16biomarker[J]．Anal Quant Cytol Histol，2008，30(2):78-82．
[137]陈恒禧,甘晓玲,傅璟.HPV L1检测预测宫颈鳞状上皮内病变预后的意义[J].现代妇产科进展,2009,18(11):865-868.
[138]张佳立,郜红艺,张江宁,等.宫颈液基细胞HPV L1壳蛋白表达的临床意义[J].诊断病理学杂志,2010,17(6):456-459.
[139]黄斌,李瑞珍,吴瑞芳,等.HPV L1壳蛋白与hTERC基因检测及联合分析对宫颈癌筛查的意义[J].华中科技大学学报，2010,39(4):554-561.
[140] Siddiqui M T,Hornaman K,Cohen C,et al.ProEx C immunocyto-chemistry andhigh-risk human papillomavirus DNA testing in papan-icolaou tests with atypicalsquamous cell(ASC-US) cytology: correla-tion study with histologic biopsy[J]ArchPathol Lab Med,2008,132(10):1648-1652.
[141] Doorbar J,The papillomavirus life cycle[J].J Clin Virol,2005,32Suppl1: S7-15.
[142] Bousarghin L,Hubert P, Franzen E,et al.Human papillomavirus16virus-like particlesuse heparan sulfates to bind dendritic cellsand colocalize with langerin inLangerhans cells[J]. J Gen Virol,2005,86(5):1297-1305.
[143] Giroglou T,Florin L,Schafer F,et al. Human Papillomavirus In-fection Requires CellSurface Heparan Sulfate[J]. J Virol,2001,75(3):1565-1570.
[144] Yoon C S,Kim K D A,Park S N,et al.alpha(6) Integrin is themain receptor of humanpapillomavirus type16VLP.[J]Biochem Bio-phys Res Commun.2001,283(3):668-673.
[145] Evander M, Frazer I H,Payne E, et al. Identification of the al-pha6integrin as acandidate receptor for papillomaviruses[J]. J Virol,1997,71(3):2449-2456.
[146] Smith J L, Campos S K, Ozbun M A. Human papillomavirus type31uses acaveolin-1and dynamin-2mediated entry pathway forinfection of humankeratinocytes[J]. J Virol,2007,81(18):9922-9931.
[147] Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis ofsimian virus40reveals a new two-step vesicular-transport path-way to the ER [J]. Nat Cell Biol,2001,3(5):473-483.
[148] Block SL,Nolan T,Sattler C,et al.Comparison of theimmunogenicity andreactogenicity of a prophylacticquadrivalent humanpapillomavirus(types6,11,16,and18)L1virus－like particle vaccine in male andfemaleadoescents and young adult women[J]．Pediatrics，2006，118(5):2135-2145．
[149]郝敏]郝敏,卞美璐.人乳头瘤病毒L1蛋白功能及其临床应用[J].中国实用妇科与产科杂志,2010，26（5）：352－355.
[150] BontkesHJ, Ruizendaal JJ,Krammer D,et a.l Plasmacytoiddendritic cells arepresent in cervical carcinoma and become acti-vated by human papillomavirus type16virus like particles[J].GynecolOnco,l2005,96(3):897-901·
[151] PintolA,Castle PE, RodenRB, eta.l HPV16L1VLP vaccineelicits a broad spectrumof cytokine responses in whole blood[J].Vaccine,2005,23(27):3555-3564·
[152] Middleton K,Peh W, Southern S A, et al. Organisation of the hu-man papillomavirusproductive cycle during neoplastic progression provides a basis for the selection ofdiagnostic markers[J]. J Virol,2003,77(19):10186-10201.
[153]张佳立,郜红艺,张江宇,吴坤河,郭玉娟,李辉斌.宫颈液基细胞HPV L1壳蛋白表达的临床意义.[J]诊断病理学杂志2010年12月第17卷第6期.
[154] Webb E,Cox J,Cervical cancer causing human papillomaviruseshave an alternativeinitiation site for the L1protein[J]. VirusGenes，2005，30(1):31－35.
[155] Yoshida T,Sano T,Kanuma T,et al．Immunochemicalanalysisof HPV L1capsidprotein and p16protein in liq-uid－based cytologysamples from uterine cervicallesions[J].Cancer，2008，114(2):83-88．
[156] Rauber D,Mehlhom G,Fasching P A,et al.Prognostic significance ofthe detection ofhuman papilloma virus L1protein in smears of mild tomoderate cervicalintraepithelial lesions[J]Eur J Obstet Gynecol Re-prod Biol,2008,140(2):258-262.
[157] Griesser H, Sander H, H ilfrich R,et al. Correlation of im munochemical detection ofHPV L1capsid p rotein in papsmears with regression of high risk HPV positivemild/moderate dysplasia [J]. Anal Quant Cytol H istol,2004,26:2412245
[158]肖巍,卞美璐,马莉,刘军,陈颖.子宫颈液基细胞学检查异常的涂片中乳头状瘤病毒L1蛋白的表达其意义[J].中华妇产科杂志,2009,44(12):887-891.
[159]黄斌,李瑞珍,刘志红,等.HPV L1壳蛋白在宫颈脱落细胞中的表达及临床意义[J].华中科技大学学报:医学版,2009,38(6):824-828.
[160] Grit Mehlhorn,Ellen Obermann,Giovanni Negri,Lukas Bubendorf,ChristineMian,Martin Koch,Heinz Sander,Birgit Simm,Markus Lütge,ZsuzsannaBánrévi, Anke Weiss,Gieri Cathomas,Ralf Hilfrich,Matthias WilhelmBeckmann and Henrik Griesser.HPV L1detection discriminates cervical precancerfrom transient HPV infection: a prospective international multicenter study.[j].Modern Pathology.10.1038.l.2012.233-240.
[161] Boulet G,Horvath C,Vanden Broeck D,et al. Humanpapillomavirus:E6and E7oncogenes[J]. Int J Biochem CellBiol，2007，39(11):2006－2011.
[162] Yoshida T,Sano T,Kanuma T,et al. Immunochemical analysisof HPVL1capsidprotein and p16protein in liquid-based cytologysamples from uterine cervicallesions[J]. Cancer,2008,114(2):83－88.
[163] Kulmala SM,Syrjanen SM,Gyllensten UB,et al. Earlyintegration of high-copy HPV16detectable in women with normaland low-grade cervical cytology and histology[J]. Clin Pathol,2006,59(5):513－517.
[164] Block SL, Nolan T,Sattler C, et al.Comparison of theimmunogenicity andreactogenicity of a prophylactic quadrivalenthuman papillomavirus (types6,11,16,and18) L1virus-likeparticle vaccine in male and female adolescents andyoung adultwomen[J].Pediatrics,2006,118(5):2135-2145.
[165] Yoshida]Tomomi Yoshida.Immunochemical analysis of HPV L1capsid protein andP16proteinin liquid-based cytology samples from uterine cervical lesions[J].CancerCytopathol,2008,114:83-88
[166]刘朝齐,许雪梅,徐建青,等.人乳头瘤病毒16型晚期基因L1在原核细胞的表达及免疫效果观察[J].中国妇幼保健，2007,22:5028-5032.
[167] Melsheimer P.Immunocytochemical detection of HPV high-risk type L1capsidproteins in LSIL and HSIL as compared with detection of HPV L1DNA[J].Acta Cytol,2003,47:124-128
[168]潘保见,陈嘉薇,祝峰.宫颈鳞癌和癌前病变中eIF-4E表达及其与HPV16/18感染的关系[J].临床与实验病理学杂志,2007,23(5):528-531
[169] Dalstein V, Riethmuller D,Pretet J L,et al.·Persistence and load of high-risk HPVare predictors for development of high-grade cervical lesions: a longitudinal Frenchcohort study[J].Int J Cancer,2003,106(3):396-403.
[170] Moberg M,Gustavsson I,Gyllensten U.Real-time PCR based sys-tem forsimultaneous quantification of human papillomavirus typesassociated with high riskof cervical cancer.[J] Clin Microbiol,2003,41(7):3221-3228.
[171] Dalstein V,Riethmuller D,Pretet JL,et al. Persistence and load of high-risk HPVare predictors for development of high-grade cer-vical lesions: a longitudinalFrench cohort study． Int [J]Cancer,2003,106(3):396-403.
[172] L EE H,L EEK J,J UNQ C K,et al1Expression of HPV L1caspid protein in cervicalspecimens with HPV infection [J] Diagn Cytopathol,2008,36(12):86428671.
[173] Li W,Wang W,Si Met al.The physical state ofHPV16infection and it clinicalsignificance in cancer precursor lesion and cervical carcinoma[J].J Cancer Res ClinOncol,2008;134(12):1355-1361
[174] Huang L W,Chao S L,Lee B H.Integration of human papillomavirus type-16andtype-18is a very early event in cervical carcinogenesis[J].J Clin Pathol,2008;61(5):627-631.
[175] Matovina M,Sabol I,Grubisic Get al.Identification of human papillo-mavirustype16integration sites in high-grade precancerous cervical le-sions[J].GynecolOncol,2009;113(1):120-127.
[176] Pett M, Coleman N. Integration of high risk human papillomavirus: a key event incervical carcinogenesis.[J] The J of Pathol.,2007,212(4),356-367
[177] Tinelli A., Vergara D,Leo G, Malvasi A, Casciaro S,Leo E.et.al.Humanpapillomavirus genital infection in modern gynecology: genetic and genomicaspects.[J] Eur Clin in Obst and Gynaecol,2007,3(1),1-6
[178] Arias-Pulido H,Peyton C.L,Joste N.E,Vargas H,Wheeler C.M. Humanpapillomavirus type16integration in cervical carcinoma in situ and in invasivecervical cancer,[J] of Clin Microbiol.,2006,44(5),1755-62.
[179] Bosch, F. X., M. M. Manos, N. Munoz, M. Sherman, A. M. Jansen, J. Peto, M. H.Schiffman, V. Moreno, R. Kurman, K. V. Shah, et al.1995. Prevalence of humanpapillomavirus in cervical cancer: a worldwide perspective.[J] Natl. CancerInst.87796-802.
[180][Pirami L,Giache V, Becciolini A. Analysis of HPV16,18,31and35DNA inpre-invasive and invasive lesions of the uterine cervix.[J]Clin Pathol1997;50:600–4.
[181] Kalantari M,Blennow E,Hagmar B, et al. Physical state of HPV16and chromosomalmapping of the integrated form in cervical carcinomas.[J]Diagn Mol Pathol2001;10:46–54.
[182] Kristiansen E, Jenkins A,Holm R.Coexistence of episomal and integrated HPV16DNA in squamous cell carcinoma of the cervix.[J] Clin Pathol1994;47:253–6.
[183] Park JS,Hwang ES,Park SN,et al.Physical status and expression of HPV genes incervical cancers.[J]Gynecol Oncol1997;65:121–129.
[184] Dürst M, Kleinheinz A, Hotz M, et al. The physical state of human papillomavirustype16DNA in benign and malignant genital tumours.[J]Gen Virol1985;66:1515–22.
[185] Castellsague, X, F. X. Bosch,and N.Munoz.2002. Environmental co-factors in HPVcarcinogenesis.[J]Virus Res.89:191-199.
[186] Munoz, N, F. X. Bosch, S. de Sanjose, R. Herrero, X. Castellsague, K. V. Shah, P. J.Snijders, and C. J.Meijer.2003. Epidemiologic classification of humanpapillomavirustypesassociatedwith cervical cancer. N. Engl.[J]. Med.348:518-527.
[187] Munoz, N., F. X. Bosch, S. de Sanjose, R. Herrero, X. Castellsague, K. V. Shah, P. J.Snijders,andC.J.Meijer.2003.Epidemiologic classification of human papillomavirustypes associated with cervical cancer. N. Engl.[J]. Med.348:518-527.
[188] Pett, M, and N. Coleman.2007. Integration of high-risk human papillomavirus: akey event in cervical carcinogenesis?[J]. Pathol.212:356-367.
[189] Jeon, S, and P. F. Lambert.1995. Integration of human papillomavirus type16DNAinto the human genome leads to increased stability of E6and E7mRNAs:implications for cervical carcinogenesis. Proc. Natl. Acad. Sci. USA92:1654-1658.
[190] Romanczuk H, and P. M. Howley.1992. Disruption of either the E1or the E2regulatory gene of human papillomavirus type16increases viral immortalizationcapacity. Proc. Natl. Acad. Sci. USA89:3159-3163.
[191] Pett, M. R., W. O. Alazawi, I. Roberts, S. Dowen, D. I. Smith, M. A. Stanley, and N.Coleman.2004. Acquisition of high-level chromosomal instability is associatedwith integration of human papillomavirus type16in cervicalkeratinocytes.[J]Cancer Res.64:1359-1368.
[192] Jeon. S, B. L. Allen-Hoffmann, and P. F. Lambert.1995. Integration of humanpapillomavirus type16into the human genome correlates with a selective growthadvantage of cells.[J]. Virol.69:2989-2997.
[193] Moscicki AB,Shiboski S,Hills NK,et a1.Regression Of low·grade squamousintra—epithelial lesions in young women.[J] Lancet.2004;364:1678-1683.
[194] Saunier M,Monnier-BenoitS,Mauny F,et aL Analysis ofhuman papillomavirustype16(HPV I6)DNA load and physical state for identification of HPV16-infectedwomen with high-gradelesions or cervical carcinoma.[J] Clin Microbi01．2008；46：3678-3685.
[195] Li W,WangW,Si M,et a1.The physical state of HPVl6infection and its clinicalsignificance in cancer precursor lesion and cervical carcinoma.[J] Cancer Res ClinOnc01.2008;134:1355-1361.
[196] Mufioz N,Bosch FX,de Sanjos6S,et a1.International Agency for Research onCancer Multicenter Cervical Cancer Study Group.[J]Epidemiologic N Engl JMed.2003;348:518·527.
[197] Badaracco G, Venuti A, Sedati A, et a.l HPV216and HPV218in genital tumors:significantly different levels of viral integration and correlation to tumorinvasiveness[J]. JMed Viro,l2002,67:5742582.
[198] Molecular Signature of HPV-Induced Carcinogenesis: pRb,p53and GeneExpression Profiling. Buitrago-Perez A,Garaulet G, Vazquez-Carballo A, ParamioJM, and Garcia-Escudero R.[J]Curr Genomics, Mar2009;10(1):26-34.
[199] Hopman AH,Smedts F,DignefW,eta1.Transition ofhigh-grade Cervicalintraepithelialneoplasia to micro-invasive carcinoma is characterized by integrationof HPV16／18and numerical chromosome abnormalities．[J] Path01.2004,202:23-33.
[200] Cricca M,Morselli-Labate AM, Venturoli S, et a.l Viral DNA load, physical statusand E2/E6ratio asmarkers to gradeHPV16positive women for high-grade cervicallesions[J].GynecolOnco,l2007,106:549-557
[201] Briolat, J., V. Dalstein, M. Saunier, K. Joseph, S. Caudroy, J. L. Pretet, P. Birembaut,and C. Clavel.2007. HPV prevalence, viral load and physical state of HPV-16incervical smears of patients with different grades of CIN. Int.[J].Cancer121.2198-2204.
[202] Cricca, M, A. M. Morselli-Labate,S. Venturoli,S. Ambretti,G. A. Gentilomi,G.Gallinella,S. Costa, M. Musiani,and M. Zerbini.2007. Viral DNA load, physicalstatus and E2/E6ratio as markers to grade HPV16positive women for high-gradecervical lesions.[J] Gynecol. Oncol.106.549-557.
[203] Gallo, G., M. Bibbo, L. Bagella, A. Zamparelli, F. Sanseverino, M. R. Giovagnoli, A.Vecchione, and A. Giordano.2003. Study of viral integration of HPV-16in youngpatients with LSIL.[J] Clin. Pathol.56532-536.
[204] Kulmala, S. M., S. M. Syrjanen, U. B. Gyllensten, I. P. Shabalova, N. Petrovichev, P.Tosi, K. J. Syrjanen, and B. C. Johansson.2006. Early integration of high copyHPV16detectable in women with normal and low grade cervical cytology andhistology.[J] Clin. Pathol.59513-517.
[205]Ga lle A.V.Boulet,Ina H. Benoy,Christophe E. Depuydt,Caroline A.J. Horvath,1MarcAerts and Johannes J. Bogers. Human Papillomavirus16Load and E2/E6RatioinHPV16-Positive Women: Biomarkers for CervicalIntraepithelial Neoplasia≥2ina Liquid-BasedCytology Setting?.[J].Cancer Epidemiol Biomarkers Prev2009;18(11)
[206] Agne Sepetiene, Zivile Gudlevicien, Zana Bumbuliene, Grazina Drasutiene,Janina Didziapetriene.State of HPV16integration in Lithuanian women withcervical neoplasia. J. Cent. Eur.[J] Med..6(2).2011.205-212.
[207] Huang L.W,Chao S.L., Lee B.H. Integration of human papillomavirus type-16and type-18is a very early event in cervical carcinogenesis.[J] ofClin Pathol.,2008,61,627-31
[208] Collins S.I.,Williams C.C.,Wen K.,Young L.S., Roberts S., Murray P.G., et.al. Disruption of the E2Gene Is a Common and Early Event in the Natural Historyof Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study,[J]Cancer Res,2009,69:(9),3828-32
[209] Longworth M.S.,Laimins L.A. Pathogenesis of human papillomaviruses indifferentiating epithelium.[J] Microbiol Mol Biol Rev.,2004,68(2),362–72。
[210] Cheung J.L.K.,Keith W.K.L.,Cheung T.H.,Tang J.W.,Chan P.K.S. Viral load,E2gene disruption status, and lineage of human papillomavirus type16infectionin cervical neoplasia.[J] of Infect Dis.,2006,194,1706–12。
[211] Wentaensen N,Vinokurova S,Magnus VKD. Systematic review of genomicintegration sites of human papilloma2virus genomes in epithelial dysplasia andinvasive cancer of the female lower genital tract[J]. Cancer Research,2004,64(6):387823884.
[212] Ga lle A.V. Boulet,1Ina H. Benoy,2Christophe E. Human Papillomavirus16Loadand E2/E6Ratio inHPV16-Positive Women: Biomarkers for CervicalIntraepithelialNeoplasia≥2in a Liquid-BasedCytology Setting?.October27,2009; DOI:10.1158/1055-9965.
[213] Bosch, F. X., M. M. Manos, N. Munoz, M. Sherman, A. M. Jansen, J. Peto, M. H.Schiffman, V. Moreno, R. Kurman, K. V. Shah, et al.1995. Prevalence of humanpapillomavirus in cervical cancer: a worldwide perspective.[J].Natl. CancerInst.87:796-802.
[214] Andersson, S., H. Safari, M. Mints,I. Lewensohn-Fuchs, U. Gyllensten, and B.Johansson.2005. Type distribution, viral load and integration status of high-riskhuman papillomaviruses in pre-stages of cervical cancer (CIN). Br.[J].Cancer92:2195-2200.
[215] Arias-Pulido,H., C. L. Peyton, N. E. Joste, H. Vargas, and C. M. Wheeler.2006.Human papillomavirus type16integration in cervical carcinoma in situ and ininvasive cervical cancer.[J]. Clin. Microbiol.44:1755-1762.
[216] Briolat, J., V. Dalstein, M. Saunier, K. Joseph, S. Caudroy, J. L. Pretet, P.Birembaut, and C. Clavel.2007. HPV prevalence, viral load and physical state ofHPV-16in cervical smears of patients with different grades of CIN. Int.[J].Cancer121:2198-2204.
[217] Cheung, J. L., K. W. Lo, T. H. Cheung, J. W. Tang, and P. K. Chan.2006.Viral load,E2gene disruption status, and lineage of human papillomavirus type16infection incervical neoplasia.[J]. Infect. Dis.194:1706-1712.
[218] Cricca, M., A. M. Morselli-Labate, S. Venturoli, S. Ambretti, G. A. Gentilomi, G.Gallinella, S. Costa, M. Musiani, and M. Zerbini.2007. Viral DNA load, physicalstatus and E2/E6ratio as markers to grade HPV16positive women for high-gradecervical lesions. Gynecol. Oncol.106:549-557.
[219] De Marco, L., A. Gillio-Tos, L. Bonello, V. Ghisetti, G. Ronco, and F.Merletti.2007. Detection of human papillomavirus type16integration inpre-neoplastic cervical lesions and confirmation by DIPS-PCR and sequencing.[J].Clin. Virol.38:7-13.
[220] Fujii, T., N. Masumoto, M. Saito, N. Hirao, S. Niimi, M. Mukai, A. Ono, S. Hayashi,K. Kubushiro, E. Sakai, K. Tsukazaki, and S. Nozawa.2005. Comparison betweenin situ hybridization and real-time PCR technique as a means of detecting theintegrated form of human papillomavirus16in cervical neoplasia. Diagn. Mol.Pathol.14:103-108.
[221] Guo, M., N. Sneige, E. G. Silva, Y. J. Jan, D. E. Cogdell, E. Lin, R. Luthra, and W.Zhang.2007. Distribution and viral load of eight oncogenic types of humanpapillomavirus (HPV) and HPV16integration status in cervical intraepithelialneoplasia and carcinoma. Mod. Pathol.20:256-266.
[222] Kulmala, S. M., S. M. Syrjanen, U. B. Gyllensten, I. P. Shabalova, N. Petrovichev,P. Tosi, K. J. Syrjanen, and B. C. Johansson.2006. Early integration of high copyHPV16detectable in women with normal and low grade cervical cytology andhistology.[J]. Clin. Pathol.59:513-517.
[223] Tonon, S. A., M. A. Picconi, P. D. Bos, J. B. Zinovich, J. Galuppo, L. V. Alonio,and A. R. Teyssie.2001. Physical status of the E2human papilloma virus16viralgene in cervical preneoplastic and neoplastic lesions. J. Clin. Virol.21:129-134.
[224] Kulmala S.M.A., Syrj nen S.M., Gyllensten U.B.,Shabalova I.P.,Petrovichev N., Tosi P. et. al. Early integration of high copy HPV16detectable in women with normal and low grade cervical cytology and histology,[J] Clin Pathol.,2006,59(5),513–517
[225]郑莹,彭芝兰,楼江燕,王和，宫颈癌及癌前病变HPV-16存在状态检测的研究[J],中国肿瘤临床,2006,33(17):961-964.
[226] Mae¨lle Saunier,Sylvain Monnier-Benoit,Fre′de′ric Mauny,et al.Analysis of HumanPapillomavirus Type16(HPV16) DNA Load and Physical State for Identification ofHPV16-Infected Women with High-Grade Lesions or CervicalCarcinoma.[J]JOURNAL OF CLINICAL MICROBIOLOGY, Nov.2008,p.3678–3685.
[227] Huang LW,Choa SL,Lee BH.Integration of human papillomavirustype-16andtype-18is a very early event in cervical carcinogenesis,[J] Clin Pathol2008;61:627-31.
[228] Peitsaro P, Johansson B, Syrjanen S. Integrated human papillomavirustype16isfrequently found in cervical cancer precursors as demon-strated by a novelquantitative real-time PCR technique.[J] Clin Micro-biol2002;40:886–91.
[229] Briolat J,Dalstein V, Saunier M, et al. HPV prevalence, viral load and physical stateof HPV-16in cervical smears of patients with differentgrades of CIN. Int J Cancer2007;121:2198–204.32. Cricca M, Morselli-Labate AM, Venturoli S, et al. ViralDNA load,physical status and E2/E6ratio as markers to grade HPV16posi-tivewomen for high-grade cervical lesions. Gynecol Oncol2007;106:549–57.
[230] De Marco L, Gillio-Tos A, Bonello L, Ghisetti V, Ronco G, Merletti F.Detection ofhuman papillomavirus type16integration in pre-neoplastic cervical lesions andconfirmation by DIPS-PCR and se-quencing.[J] Clin Virol2007;38:7–13.
[231] Andersson S, Safari H, Mints M, Lewensohn-Fuchs I, Gyllensten U,Johansson B.Type distribution, viral load and integration state ofhigh-risk humanpapillomaviruses in pre-stages of cervical cancer(CIN).Br J Cancer2005;92:2195–200.
[232] Gallo G, Bibbo M,Bagella L, et al. Study of viral integration of HPV-16in youngpatients with LSIL.[J] Clin Pathol2003;56:532–6.
[233] Bauknecht T,Jundt F, Herr I,et al.A switch region determines the celltype-specificpositive or negative action of YY1on the activity of thehuman papillomavirus type18promotor.[J] Virol1995;69:1–12.
[234] Jundt F,Herr I,Angel P,Zur Hausen H, Bauknecht T. Transcriptionalcontrol ofhuman papillomavirus type18oncogene expression in dif-ferent cell lines: role oftranscription factor YY1.[J]Virus Genes1995;11:53–8.
[235] Bhattacharjee B, Sengupta S. CpG methylation of HPV16LCR at E2binding siteproximal to P97is associated with cervical cancer in pres-ence of intact E2.Virology2006;354:280–5.
[236] Arias-PulidoH,Peyton CL,JosteNE,et a.lHuman papillo-mavirus type16integrationin cervical carcinoma in situand in invasive cervical cancer[J].Clin Microbio,l2006,44:1755-1762.
[237]张帅,蔡红兵,丁晓华。HPV16E2基因各区域缺失与宫颈病变相关性的研究.[J]现代妇产科进展2010年10月第19卷第10期.
[238] Mingjun Jiang,Janet G.Baseman, Laura A.Koutsky, Qinghua Feng,ConstanceMao, Nancy B.Kiviat,and Long Fu Xi.Sequence Variation of HumanPapillomavirus Type16and Measurement of Viral Integration by Quantitative PCR.[J]. J Clin Microbiol.2009March;47(3):521–526.
[239] J. Peto, C.Gilham, O.Fletcher and F.E. Matthews, Thecervical cancer epidemic thatscreening has prevented in theUK.[J] Lancet364(2004),249–256.
[240]时艳梅,叶红,肖长义,等,宫颈病变患者病变组织HPV整合状态的变化及意义[J],山东医药,2009年,第49第6期.
[1] Doorbar J. Molecular biology of human papillomavirus infectionand cervical cancer[J].Clin Sci (Lond),2006,110(5):525-541.
[2] Lukaszuk K, Liss J, Woznia I,et al. Human papillomavirus type16status in cervicalcarcinoma cell DNA assayed by multiplex PCR[J].Journal of ClinicalMicrobiology,2003,41(2):608-612.
[3]徐海燕,辛晓燕.人乳头瘤病毒感染与宫颈癌的研究进展［J］.中国妇幼健康研究，2007，18(5):436-440.
[4]宋国兴.子宫颈癌致病因子人乳头瘤病毒的发现［J］.科技导报,2008,26(24):31-36.
[5] Bousarghin L, Hubert P, Franzen E,et al. Human papillomavirus16virus-like particlesuse heparan sulfates to bind dendritic cellsand colocalize with langerin in Langerhanscells[J]. J Gen Virol,2005,86(5):1297-1305.
[6] Giroglou T, Florin L, Schafer F, et al. Human Papillomavirus In-fection Requires CellSurface Heparan Sulfate[J]. J Virol,2001,75(3):1565-1570.
[7] Yoon C S, Kim K D A,Park S N, et al. alpha(6) Integrin is themain receptor of humanpapillomavirus type16VLP.Biochem Bio-phys Res Commun[J].2001,283(3):668-673.
[8] Evander M, Frazer I H, Payne E, et al. Identification of the al-pha6integrin as acandidate receptor for papillomaviruses[J]. JVirol,1997,71(3):2449-2456.
[9] Smith J L, Campos S K, Ozbun M A. Human papillomavirus type31uses a caveolin-1and dynamin-2mediated entry pathway forinfection of human keratinocytes[J]. JVirol,2007,81(18):9922-9931.
[10] Pelkmans L, Kartenbeck J, Helenius A.Caveolar endocytosis ofsimian virus40reveals a new two-step vesicular-transport path-way to the ER [J]. Nat Cell Biol,2001,3(5):473-483.
[11]Henrik Griesser,Heinz Sander, Cindy Walczak, et al. HPV Vaccine Protein L1PredictsDisease Outcome of High-Risk HPV+Early Squamous Dysplastic Lesions.Am J ClinPathol[J]. Nat Cell Biol,2009,132:840-845.
[12] Middleton K,Peh W, Southern S A, et al.Organisation of the hu-man papillomavirusproductive cycle during neoplastic progressionprovides a basis for the selection ofdiagnostic markers[J]. J Virol,2003,77(19):10186-10201.
[13] Hopman A, Smedts F, Dignef W, et al. Transition of high-gradecervical intraepithelialneoplasia to micro-invasive carcinoma ischaracterized by integration of HPV16/18and numerical chromo-some abnormalities[J]. J Pathol,2004,202:23-33.
[14][Klaes R,Friedrich T,Spikovsky D.et a1.Overexpression ofpl61NK4a as a specificmarker fordysplastic and neoplastic ep—ithelial cells of the cervic uteri[J].Int JCancer,2001,92(2)：276-284.
[15] Kim NR,Lin z,Kim KR,et a1.EpsteimBarr virus and P161”“4methylationinsquamouscell carcinoma andprecancerous lesions ofthe cervix uteri[J]J KoreanMed Sci,005．20(4)：636-642．
[16] KalofAN,CooperK.P161NK4a immunoexpression：surrogatemarker of high-risk HPVand high-grade cervical intraepithelialneoplasia[J] Adv Anat Pathol,2006,13(4)：190-194．
[17] Von Knebel-Doeh(，ritz M New marks for cervical dysplasia to vis—ualizethegeoonucchaos created by aberrant oncogenic papilloma—virus infections[J]．Eur JCanee.2002,38：2229-2242.
[18] Volgareva G,Zavalishina L,Andreeva Y.et a1.Protein p16as amarkerofdysplasticandneoplasticalterations in cervical epithelialcells[J]BMCCancer,2004,4(I)：58-65.
[19] Davidson EJ,Morris LS,Scott IS,et al.Minichromosomemaintenance(Mcm)proteins,cyclin B1and D1,phospho-histone H3and in situ DNA replication forfunctional a-nalysis of vulval intraepithelial neoplasia［J］Br J Canc-er,2003,88(2):257-262.
[20] Gupta N,Srinivasan R,Rajwanshi A. Functional biomarkers in cervical precancer：Anoverview［JDiagn Cytopathol,2010,38（8）：618~623.
[21] Mulvany NJ,Allen DG,Wilson SM. Diagnostic utility of p16INK4a: a reappraisal of itsuse in cervical biopsies ［J］. Pathology，2008，40（4）：335～344.
[22] Tsoumpou I,Arbyn M,Kyrgiou M,et al. p16（INK4a) immunostainingin cytologicaland histological specimens from the uterine cervix: asystematic review andmeta-analysis.Cancer［J］.Treat Rev,2009,35（3）：210～220.
[23]黄惠英,钱德英,岑坚敏.免疫组化P16蛋白在不同级别宫颈病变中表达差异的研究［J］.现代医院,2008,8（3）：14～15.
[24] O'Neill CJ,McCluggage WG.p16expression in the female genitaltract and its value indiagnosi［J］. Adv Anat Pathol,2006,13（1）：8～15.
[25] Sung CO,Kim SR,Oh YL,et al.The use of p16（INK4A）immunocytochemistry in"Atypical squamous cells which cannotexclude HSIL" compared with "Atypicalsquamous cells ofundetermined significance" in liquid-based cervical smears［J］Diagn Cytopathol,2010,38（3）：168～171.
[26] Focchi GR,Silva ID,Nogueira-de-Souza NC,et al.Immunohistochemical expressionof p16（INK4A） in normal uterine cervix，nonneoplastic epithelial lesions， andlow-grade squamousintraepithelial lesions［J］. Low Genit Tract Dis,2007,11（2）：98～104.
[27] Yildiz IZ,Usubutun A,FiratP, et a.l Efficiency of immu-nohistochemical p16expression andHPV typing in cervi-cal squamous intraepithelial lesion grading andreview ofthe p16literature[J]. PatholRes Prac Vo,l2007,203:445-449.
[28] Negri G, Egarter-Vigl E, KasalA, et a.l p16INK4a is ausefulmarker for the diagnosisof adenocarcinoma of thecervix uteri and its precursors: animmunohistochemicalstudywith immunocyto-chemical correlations[J]. Am JSurgPatho,l2003,27:187-193
[29] ON' eill CJ,McCluggageWG. p16expression in the fe-male genital tract and its valuein diagnosis[J]. AdvAnatPatho,l2006,13:1-8
[30] HilfrichR,Hariri J. Prognostic relevance ofhuman papil-lomavirus L1capsid proteindetection within mild andmoderate dysplastic lesions of the cervix uteri incombi-nation with p16biomarker[J].AnalQuantCytolHisto,l2008,30:78-82.
[31] Yoshida T, Sano T,Kanuma T, et a.l Immunochemical a-nalysis ofHPV L1capsidprotein and p16protein in liq-uid-based cytology samples from uterine cervicallesions [J].Cancer,2008,11:83-88
[32] Yu R, HeaneyAP, LuW, et a,l Pi tui tary tumor t rahs forming genecauses aneuploidyand p53-dependent and p53-independent apoptosis[J].J BiolChem,2000,275:36502-36505.
[33]靳玉兰,张伟,刘伯齐,等.食管癌前病变及原位癌组织中Ki67、p53、iNOS的异常表达[J].中华肿瘤杂志,2001,23(2):129-131.
[34] Salvesen HB,Iversen0E,Akslen L A.Prognostic significance of an-giogenesis andKi67,P53,and P21expression：a population based endometrial carcinoma study[J]．JChin0ncol,1999,17：1382.
[35]李东辉,李明众.张薛榜．口一catenin和ki-67在人宫颈癌组织中的表达及其意义[J].实用癌症杂志.2007,22(1)：28-30．
[36] GAOP.ZH()U GY.Y1N G,et aI.Lymphatic vessel density asa prognostic indicator forpatients with stage I cervicalcarcinoma[J].Human Pathology．2006．37(6)：719-725.
[37] Van de PUTTE G,KRlsTENsEN GB,LIE AK,et a1.CycIinsand proliferation markersin early squamous cervicalcarcinorna[J]Gynecologic(hcoIogy，2004，92(1)：40-46．2.3.
[38] Shroyer KR,Homer P, Heinz D, et al. Validation of a novel immunocytochemicalassay for topoisomerase II-a and minichromosome maintenance protein2expressionin cervical cytology.[J]Cancer2006;108:324–330.
[39] Kelly D,Kincaid E, Fansler Z, et al. Detection of cervical high-grade squamousintraepithelial lesions from cytologic samples using a novel immunocytochemicalassay (ProEx C). Cancer2006;108:494–500.
[40] Badr RE,Walts AE, Chung F, et al. BD ProExC: a sensitive and specific marker ofHPV-associated squamous lesions of the cervix. Am J Surg Pathol2008;32:899–906.
[41] Chan KY, Walts AE, Bose S. ProExC is a marker for HPV-associated anal lesions.[J]Mod Pathol2007;20(Suppl2):109A.
[42]张桂香,赵学东,赵卫平.MCM2蛋白在肿瘤中的表达及意义［J］.现代肿瘤医学,2008，16(12):2210-2212
[43] Badr RE,Waltes AE,Chung F,et al.BD ProEx C: A Sen-sitive and specific marker ofHPV-associated squamous le-sions of the cervix［J］Am J Surg Path.2008,32(6):899-906.
[44] Mukherjee G,Muralidhar B,Bafna UD,et al.Mcm immu-nocytochemistry as a first linecervical screening test indeveloping countries: a prospective cohort study in are-gional cancer centre in India［J］．Br J Cancer,2007,96(7),1107-1111.
[45] Shroyer KR,Homer P,Heinz D,et al, Validationofa novelimmunocytochemical assayfor topoisomerase Ⅱ-alphaand minichromosome maintenance protein2expressionincervical cytology［J］Cancer,2006,108(5):324-330.
[46] Aximu D,Azad A,Ni R,et al.A pilot evaluation of a no-vel immunohistochemicalassay for topoisomerase Ⅱ-al-pha and minichromosome maintenance protein2expres-sion(ProEx C) in cervical adenocarcinoma in situ，adeno-carcinoma，andbenign glandular mimics［J］Int J Gyne-col Pathol,2009,28(2):114-119.
[47] Mukherjee G,Freeman A,Moore R,et al.Biologic factorsand response to radiotherapyin carcinoma of the cervix［J］.Int J Gynecol Cancer,2001,11(3):187-193.
[48] Kato K,Toki T,Shimizu M,et al.Expression of replica-tion-licensing factors MCM2and MCM3in normal,hy-perplastic,and carcinomatous endometrium: correlationwithexpression of Ki-67and estrogen and progesteronereceptors［J］. Int J GynecolPathol,2003,22(4):334-340.
[49] Kulkarni AA,Loddo M,Leo E,et al.DNA replication li-censing factors and aurorakinases are linked to aneu-ploidy and clinical outcome in epithelial ovariancarcino-ma［J］.Clin Cancer Res,2007,13(20):6153-6161.
[50] Gakiopoulou H,Korkolopoulou P,Levidou G,et al.Mini-chromosome maintenanceproteins2and5in non-benignepithelial ovarian tumours: relationship with cellcycleregulators and prognostic implications［J］.Br J Cancer,2007,97(8):1124-1134.