人乳头瘤病毒的悬浮芯片分型及其临床意义

详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文

英文题名：Human Papillomavirus Genotyping and Its Clinical Significance 作者：蒋汉梁 论文级别：博士 学科专业名称：内科学 学位年度：2008 导师：陈智 学科代码：100201 学位授予单位：浙江大学 论文提交日期：2008-06-01

摘要

人乳头瘤病毒(Human Papillomavirus,HPV)感染是宫颈癌发生的必要因素,宫颈癌是严重威胁我国女性健康的妇科常见恶性肿瘤。流行病学研究表明,高危型HPV的持续感染是宫颈癌形成的最主要因素。早期发现宫颈高危型HPV感染与准确分型,及时进行早期干预治疗,是提高宫颈癌防治效果的有效途径。
     为了建立一种快速高通量的HPV分型检测方法,本研究以悬浮芯片技术为平台,分别设计HPV型特异性探针,并分别联结至不同编号的微球上,在不断优化杂交反应条件后,建立了一种快速高通量的HPV分型检测方法(HPVsuspension array,HPV-SA):通过对HPV基因型标准品的检测,证实本法所使用的探针具有高的特异性,各探针间未见有交叉反应;进一步对720例临床样本进行检测,证实HPV-SA能够快速准确地检测临床样本的HPV感染型别;以E7型特异性PCR法和DNA测序法作为检测的“金标准”,证实HPV-SA法的检测灵敏度为86.14%,特异度为98.26%,阳性预测值为95.08%,阴性预测值为92.92%,一致性为94.86%。
     为了获得本地区HPV亚型感染情况的信息,以及了解宫颈病变严重程度与HPV感染亚型之间的关系。本研究采用已建立的高通量HPV-SA法,对Normal,CINⅠ,CINⅡ,CINⅢ和Carcinoma等各种宫颈病理组织进行了HPV的感染情况研究;发现本地区HPV总体感染情况,是以HPV16的感染率为最高,其次为HPV58和HPV18;在Normal、CINⅠ、CINⅡ和CINⅢ组织以HPV16、58的感染为主,而在Carcinoma组织则以HPV16、18的感染为主;高危型HPV的单纯感染率要显著高于混合感染率;病变越是严重的组织,其高危型HPV的感染率就越高。这些信息的获得,为本地区更有针对性的宫颈防癌筛查策略的制定打下了基础,也为更具针对性的HPV疫苗的设计提供了重要的信息。
Cervical cancer,a common gynecologic malignancy,is a serious threat to women's health in china.Epidemiological studies have shown that the persistent infection of high-risk HPV is the most important factor for cervical cancer formation. The effective way to decrease the cervical cancer morbidity is to detect and classify the high-risk HPV infection in early time.
     In this study,we have established a rapid high-throughput HPV genotyping method by using the suspension array technology(HPV suspension array,HPV-SA). The specificity had been confirmed by the hybridization between probes and standard samples.Experiments show that HPV-SA can quickly and accurately detect 720 clinical samples.The detection accuracy of HPV using HPV-SA for 720 samples was as follows:sensitivity 86.14%,specificity 98.26%,positive predictive value 95.08%,the negative predictive value 92.92%,consistency 94.86%.
     In order to obtain subtypes information of HPV infection in the region,as well as understand the relationships between HPV subtypes and cervical lesions.We have studied on the HPV prevalence in different cervical lesions by using the HPV-SA method.Experiments show that the major prevalent high-risk HPV subtypes were HPV16,58 and 18 in normal,CINⅠ,CINⅡand CINⅢtissues,while in carcinoma tissue were HPV16 and 18.The single infection rate was significantly higher than multiple infections in all lesions.This information can improve the effect of cervical cancer screening,as well as provide important information for HPV vaccine design.

引文

1.Schoell W.M.,Janicek M.F.,and Mirhashemi R.,Epidemiology and biology of cervical cancer.Semin Surg Oncol,1999.16(3):p.203-11.
    2.Jansen K.U.,Toward vaccines against cervical cancer.Curr Opin Drug Discov Devel,2004.7(2):p.228-32.
    3.Yang L.,Parkin D.M.,Li L.,et al.,Time trends in cancer mortality in China:1987-1999.Int J Cancer,2003.106(5):p.771-83.
    4.Chen X.S.,Gong X.D.,Liang G.J.,et al.,Epidemiologic trends of sexually transmitted diseases in China.Sex Transrn Dis,2000.27(3):p.138-42.
    5.Sherman M.E.,Mendoza M.,Lee K.R.,et al.,Performance of liquid-based,thin-layer cervical cytology:correlation with reference diagnoses and human papillomavirus testing.Mod Pathol,1998.11(9):p.837-43.
    6.Hutchinson M.L.,Zahniser D.J.,Sherman M.E.,et al.,Utility of liquid-based cytology for cervical carcinoma screening:results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma.Cancer,1999.87(2):p.48-55.
    7.Soler M.E.and Blumenthal P.D.,New technologies in cervical cancer precursor detection.Curr Opin Oncol,2000.12(5):p.460-5.
    8.Holladay E.B.and Allen K.A.,A new era for the Pap test.Jaapa,2001.14(12):p.53-6.
    9.Vassilakos P.,Petignat P.,Boulvain M.,et al.,Primary screening for cervical cancer precursors by the combined use of liquid-based cytology,computer-assisted cytology and HPV DNA testing.Br J Cancer,2002.86(3):p.382-8.
    10.Pan Q.,Belinson J.L.,Li L.,et al.,A thin-layer,liquid-based pap test for mass screening in an area of China with a high incidence of cervical carcinoma.A cross-sectional,comparative study.Acta Cytol,2003.47(1):p.45-50.
    11.Depuydt C.E.,Vereecken A.J.,Salembier G.M.,et al.,Thin-layer liquid-based cervical cytology and PCR for detecting and typing human papillomavirus DNA in Flemish women.Br J Cancer,2003.88(4):p.560-6.
    12.Weynand B.,Berliere M.,Haumont E.,et al.,A new,liquid-based cytology technique.Acta Cytol,2003.47(2):p.149-53.
    13.Solomon D.,Davey D.,Kurman R.,et al.,The 2001 Bethesda System:terminology for reporting results of cervical cytology.Jama,2002.287(16):p.2114-9.
    14.Brown D.R.,Bryan J.T.,Cramer H.,et al.,Analysis of human papillomavirus types in exophytic condylomata acuminata by hybrid capture and Southern blot techniques.J Clin Microbiol,1993.31(10):p.2667-73.
    15.Evans M.F.,Adamson C.S.,Papillo J.L.,et al.,Distribution of human papillomavirus types in ThinPrep Papanicolaou tests classified according to the Bethesda 2001terminology and correlations with patient age and biopsy outcomes.Cancer,2006.106(5):p.1054-64.
    16.Peto J.,Gilham C.,Fletcher O.,et al.,The cervical cancer epidemic that screening has prevented in the UK.Lancet,2004.364(9430):p.249-56.
    17.Pham T.H.,Nguyen T.H.,Herrero R.,et al.,Human papillomavirus infection among women in South and North Vietnam.Int J Cancer,2003.104(2):p.213-20.
    18.Sukvirach S.,Smith J.S.,Tunsakul S.,et al.,Population-based human papillomavirus prevalence in Lampang and Songkla,Thailand.J Infect Dis,2003.187(8):p.1246-56.
    19.Clifford G.M.,Smith J.S.,Plummer M.,et al.,Human papillomavirus types in invasive cervical cancer worldwide:a meta-analysis.Br J Cancer,2003.88(1):p.63-73.
    20.Munoz N.,Bosch F.X.,de Sanjose S.,et al.,Epidemiologic classification of human papillomavirus types associated with cervical cancer.N Engl J Med,2003.348(6):p.518-27.
    21.Schiffman M.and Castle P.E.,Human papillomavirus:epidemiology and public health.Arch Pathol Lab Med,2003.127(8):p.930-4.
    22.Liaw K.L.,Glass A.G.,Manos M.M.,et al.,Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.J Natl Cancer Inst,1999.91(11):p.954-60.
    23.Schlecht N.F.,Kulaga S.,Robitaille J.,et al.,Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.Jama,2001.286(24):p.3106-14.
    24.Kjaer S.K.,van den Brule A.J.,Paull G.,et al.,Type specific persistence of high risk human papillomavirus(HPV)as indicator of high grade cervical squamous intraepithelial lesions in young women:population based prospective follow up study Bmj,2002.325(7364):p.572.
    25.Cox J.T.,Human papillomavirus testing in primary cervical screening and abnormal Papanicolaou management.Obstet Gynecol Surv,2006.61(6 Suppl 1):p.S15-25.
    26.Kuhn L.,Denny L.,Pollack A.,et al.,Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.J Natl Cancer Inst,2000.92(10):p.818-25.
    27.Bernard H.U.,The clinical importance of the nomenclature,evolution and taxonomy of human papillomaviruses.J Clin Virol,2005.32 Suppl 1:p.S1-6.
    28.Nobbenhuis M.A.,Walboomers J.M.,Helmerhorst T.J.,et al.,Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening:a prospective study.Lancet,1999.354(9172):p.20-5.
    29.Tsai H.T.,Wu C.H.,Lai H.L.,et al.,Association between quantitative high-risk human papillomavirus DNA load and cervical intraepithelial neoplasm risk.Cancer Epidemiol Biomarkers Prey,2005.14(11 Pt1):p.2544-9.
    30.Tsuda H.,Hashiguchi Y.,Nishimura S.,et al.,Relationship between HPV typing and abnormality of G1 cell cycle regulators in cervical neoplasm.Gynecol Oncol,2003.91(3):p.476-85.
    31.Kiatpongsan S.,Niruthisard S.,Mutirangura A.,et al.,Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance.Int J Gynecol Cancer,2006.16(1):p.262-5,
    32.Andersson S.,Safari H.,Mints M.,et al.,Type distribution,viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer(CIN).Br J Cancer,2005.92(12):p.2195-200.
    33.Wang S.S.,Schiffman M.,Shields T.S.,et al.,Seroprevalence of human papillomavirus-16,-18,-31,and-45 in a population-based cohort of 10000 women in Costa Rica.Br J Cancer,2003.89(7):p.1248-54.
    34.Munoz N.,Castellsague X.,de Gonzalez A.B.,et al.,Chapter 1:HPVin the etiology of human cancer.Vaccine,2006.24S3:p.S1-S10.
    35.Tase T.,Okagaki T.,Clark B.A.,et al.,Human papillomavirus DNA in adenocarcinoma in situ,microinvasive adenocarcinoma of the uterine cervix,and coexisting cervical squamous intraepithelial neoplasia.Int J Gynecol Pathol,1989.8(1):p.8-17.
    36.Walboomers J.M.,Jacobs M.V.,Manos M.M.,et al.,Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.J Pathol,1999.189(1):p.12-9.
    37.Bulk S.,Berkhof J.,Bulkmans N.W.,et al.,Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands.Br J Cancer,2006.94(1):p.171-5.
    38.Tase T.,Okagaki T.,Clark B.A.,et al.,Human papillomavirus types and localization in adenocarcinoma and adenosquamous carcinoma of the uterine cervix:a study by in situ DNA hybridization.Cancer Res,1988.48(4):p.993-8.
    39.Tase T.,Sato S.,Wada Y.,et al.,Prevalence of human papillomavirus type 18 DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix occurring in Japan.Tohoku J Exp Med,1988.156(1):p.47-53.
    40.Reeves W.C.,Caussy D.,Brinton L.A.,et al.,Case-control study of human papillomaviruses and cervical cancer in Latin America.Int J Cancer,1987.40(4):p.450-4.
    41.Senba M.,Kumatori A.,Fujita S.,et al.,The prevalence of human papillomavirus genotypes in penile cancers from northern Thailand.J Med Virol,2006.78(10):p.1341-6.
    42.Castellsague X.,Klaustermeier J.,Carrilho C.,et al.,Vaccine-related HPV genotypes in women with and without cervical cancer in Mozambique:burden and potential for prevention.Int J Cancer,2008.122(8):p.1901-4.
    43.Vaccarella S.,Lazcano-Ponce E.,Castro-Garduno J.A.,et al.,Prevalence and determinants of human papillomavirus infection in men attending vasectomy clinics in Mexico.Int J Cancer,2006.119(8):p.1934-9.
    44.Bell M.C.,Schmidt-Grimminger D.,Patrick S.,et al.,There is a high prevalence of human papillomavirus infection in American Indian women of the Northern Plains.Gynecol Oncol,2007.107(2):p.236-41.
    45.Bao Y.P.,Li N.,Smith J.S.,et al.,Human papillomavirus type-distribution in the cervix of Chinese women:a meta-analysis.Int J STD AIDS,2008.19(2):p.106-11.
    46.Li Y.,Wang Y.,Jia C.,et al.,Detection of human papillomavirus genotypes with liquid bead microarray in cervical lesions of northern Chinese patients.Cancer Genet Cytogenet,2008.182(1):p.12-7.
    47.Hong D.,Ye F.,Chen H.,et al.,Distribution of human papillomavirus genotypes in the patients with cervical carcinoma and its precursors in Zhejiang Province,China.Int J Gynecol Cancer,2008.18(1):p.104-9.
    48.Dai Y.,Huang Y.S.,Tang M.,et al.,Distribution and clinical significance of human papillomavirus subtypes in Shenzhen city,People's Republic of China.Int J Gynecol Cancer,2008.18(2):p.295-9.
    49.Wu R.F.,Dai M.,Qiao Y.L.,et al.,Human papillomavirus infection in women in Shenzhen City,People's Republic of China,a population typical of recent Chinese urbanisation.Int J Cancer,2007.121(6):p.1306-11.
    50.Brink A.A.,Snijders P.J.,and Meijer C.J.,HPV detection methods.Dis Markers,2007.23(4):p.273-81.
    51.Dunbar S.A.,Vander Zee C.A.,Oliver K.G.,et al.,Quantitative,multiplexed detection of bacterial pathogens." DNA and protein applications of the Luminex LabMAP system.J Microbiol Methods,2003.53(2):p.245-52.
    1.Bernard H.U.,The clinical importance of the nomenclature,evolution and taxonomy of human papillomaviruses.J Clin Virol,2005.32 Suppl 1:p.S1-6.
    2.Munoz N.,Bosch F.X.,de Sanjose S.,et al.,Epidemiologic classification of human papillomavirus types associated with cervical cancer.N Engl J Med,2003.348(6):p.518-27.
    3.Qureshi M.N.,Rudelli R.D.,Tubbs R.R.,et al.,Role of HPV DNA testing in predicting cervical intraepithelial lesions:comparison of HC HPV and ISH HPV.Diagn Cytopathol,2003.29(3):p.149-55.
    4.Hesselink A.T.,van den Brule A.J.,Brink A.A.,et al.,Comparison of hybrid capture 2 with in situ hybridization for the detection of high-risk human papillomavirus in liquid-based cervical samples.Cancer,2004.102(1):p.11-8.
    5.Hopman A.H.,Smedts F.,Dignef W.,et al.,Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities.J Pathol,2004.202(1):p.23-33.
    6.Kerstens H.M.,Poddighe P.J.,and Hanselaar A.G.,A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine.J Histochem Cytochem,1995.43(4):p.347-52.
    7.Schneider A.,Kraus H.,Schuhmann R.,et al.,Papillomavirus infection of the lower genital tract." detection of viral DNA in gynecological swabs.Int J Cancer,1985.35(4):p.443-8.
    8.Okagaki T.,Twiggs L.B.,Zachow K.R.,et al.,Identification of human papillomavirus DNA in cervical and vaginal intraepithelial neoplasia with molecularly cloned virus-specific DNA probes.Int J Gynecol Pathol,1983.2(2):p.153-9.
    9.Grussendorf-Conen E.I.,Ikenberg H.,and Gissmann L.,Demonstration of HPV-16genomes in the nuclei of cervix carcinoma cells.Dermatologica,1985.170(4):p. 199-201.
    10.SchoU S.M.,Pillers E.M.,Robinson R.E.,et al.,Prevalence of human papillomavirus type 16 DNA in cervical carcinoma samples in East Anglia.Int J Cancer,1985.35(2):p.215-8.
    11.Loning T.,Ikenberg H.,Becker J.,et al.,Analysis of oralpapillomas,leukoplakias,and invasive carcinomas for human papillomavirus type related DNA.J Invest Dermatol,1985.84(5):p.417-20.
    12.Fukushima M.,Okagaki T.,Twiggs L.B.,et al.,Histological types of carcinoma of the uterine cervix and the detectability of human papillomavirus DNA.Cancer Res,1985.45(7):p.3252-5.
    13.Naghashfar Z.,Sawada E.,Kutcher M.J.,et al.,Identification of genital tract papillomaviruses HPV-6 and HPV-16 in warts of the oral cavity.J Med Virol,1985.17(4):p.313-24.
    14.Gravitt P.E.,Peyton C.L.,Apple R.J.,et al.,Genotyping of 27 humanpapillomavirus types by using L1 consensus PCR products by a single-hybridization,reverse line blot detection method J Clin Microbiol,1998.36(10):p.3020-7.
    15.Tieben L.M.,ter Schegget J.,Minnaar R.P.,et al.,Detection of cutaneous and genital HPV types in clinical samples by PCR using consensus primers.J Virol Methods,1993.42(2-3):p.265-79.
    16.van den Brule A.J.,Pol R.,Fransen-Daalmeijer N.,et al.,GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes.J Clin Microbiol,2002.40(3):p.779-87.
    17.Gregoire L.,Arella M.,Campione-Piccardo J.,et al.,Amplification of human papillomavirus DNA sequences by using conserved primers.J Clin Microbiol,1989.27(12):p.2660-5.
    18.Kleter B.,van Doom L.J.,Schrauwen L.,et al.,Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus.J Clin Microbiol,1999.37(8):p. 2508-17.
    19.Gravitt P.E.,Peyton C.L.,Alessi T.Q.,et al.,Improved amplification of genital humanpapillomaviruses.J Clin Microbiol,2000.38(1):p.357-61.
    20.Monsonego J.,Bohbot J.M.,Pollini G.,et al.,Performance of the Roche AMPLICOR human papillomavirus(HPV)test in prediction of cervical intraepithelial neoplasia (CIN)in women with abnormal PAP smear.Gynecol Oncol,2005.99(1):p.160-8.
    21.Walboomers J.M.,Jacobs M.V.,Manos M.M.,et al.,Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.J Pathol,1999.189(1):p.12-9.
    22.Josefsson A.,Livak K.,and Gyllensten U.,Detection and quantitation of human papillomavirus by using the fluorescent 5' exonuclease assay.J Clin Microbiol,1999.37(3):p.490-6.
    23.Hesselink A.T.,van den Brule A.J.,Groothuisrnink Z.M.,et al.,Comparison of three different PCR methods for quantifying human papillomavirus type 16 DNA in cervical scrape specimens.J Clin Microbiol,2005.43(9):p.4868-71.
    24.Moberg M.,Gustavsson I.,and Gyllensten U.,Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer.J Clin Microbiol,2003.41(7):p.3221-8.
    25.Josefsson A.M.,Magnusson P.K.,Ylitalo N.,et al.,Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ:a nested case-control study.Lancet,2000.355(9222):p.2189-93.
    26.Ylitalo N.,Sorensen P.,Josefsson A.M.,et al.,Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ:a nested case-control study.Lancet,2000.355(9222):p.2194-8.
    27.van Duin M.,Snijders P.J.,Schrijnemakers H.F.,et al.,Human papillomavirus 16load in normal and abnormal cervical scrapes:an indicator of CIN Ⅱ/Ⅲ and viral clearance.Int J Cancer,2002.98(4):p.590-5.
    28.Snijders P.J.,Hogewoning C.J.,Hesselink A.T.,et al.,Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16,18,31 and 33-positive women with normal cytology.Int J Cancer,2006.119(5):p.1102-7.
    29.Snijders P.J.,van den Brule A.J.,and Meijer C.J.,The clinical relevance of human papillomavirus testing:relationship between analytical and clinical sensitivity.J Pathol,2003.201(1):p.1-6.
    30.Daponte A.,Pournaras S.,Mademtzis I.,et al.,Evaluation of high-risk human papillomavirus types PCR detection in paired urine and cervical samples of women with abnormal cytology.J Clin Virol,2006.36(3):p.189-93.
    31.Szuhai K.,Sandhaus E.,Kolkman-Uljee S.M.,et al.,A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction.Am J Pathol,2001.159(5):p.1651-60.
    32.Clavel C.,Masure M.,Putaud Ⅰ.,et al.,Hybrid capture Ⅱ,a new sensitive test for human papillomavirus detection.Comparison with hybrid capture Ⅰ and PCR results in cervical lesions.J Clin Pathol,1998.51(10):p.737-40.
    33.Nindl I.,Greinke C.,Zahm D.M.,et al.,Human papillomavirus distribution in cervical tissues of different morphology as determined by hybrid capture assay and PCR.Int J Gynecol Pathol,1997.16(3):p.197-204.
    34.Brown D.R.,Pratt L.,Fife K.H.,et al.,Temporal and histologic relationships of proliferating cell nuclear antigen and human papillomavirus type Ⅱ in the mouse xenografisystem.J Med Virol,1996.48(1):p.108-13.
    35.Kulmala S.M.,Syrjanen S.,Shabalova I.,et al.,Human papillomavirus testing with the hybrid capture 2 assay and PCR as screening tools.J Clin Microbiol,2004.42(6):p.2470-5.
    36.Clavel C.,Bory J.P.,Rihet S.,et al.,Comparative analysis of human papillomavirus detection by hybrM capture assay and routine cytologic screening to detect high-grade cervical lesions.Int J Cancer,1998.75(4):p.525-8.
    37.Carvalho M.O.,Almeida R.W.,Leite F.M.,et al.,Detection of human papillomavirus DNA by the hybrid capture assay.Braz J Infect Dis,2003.7(2):p.121-5.
    38.Farthing A.,Masterson P.,Mason W.P.,et al.,Human papillomavirus detection by hybrid capture and its possible clinical use.J Clin Pathol,1994.47(7):p.649-52.
    39.KIaassen C.H.,Prinsen C.F.,de Valk H.A.,et al.,DNA microarray format for detection and subtyping of human papillomavirus.J Clin Microbiol,2004.42(5):p.2152-60.
    40.Oh T.J.,Kim C.J.,Woo S.K.,et al.,Development and clinical evaluation of a highly sensitive DNA microarray for detection and genotyping of human papillomaviruses.J Clin Microbiol,2004.42(7):p.3272-80.
    41.Perrons C.,Kleter B.,Jelley R.,et al.,Detection and genotyping of human papillomavirus DNA by SPFIO and MY09/11 primers in cervical cells taken from women attending a colposcopy clinic.J Med Virol,2002.67(2):p.246-52.
    42.De Francesco M.A.,Gargiulo F.,Schreiber C.,et al.,Detection and genotyping of human papillomavirus in cervical samples from Italian patients.J Med Virol,2005.75(4):p.588-92.
    43.van Ham M.A.,Bakkers J.M.,Harbers G.K.,et al.,comparison of two commercial assays for detection of human papillomavirus(HPV)in cervical scrape specimens:validation of the Roche AMPLICOR HPV test as a means to screen for HPV genotypes associated with a higher risk of cervical disorders.J Clin Microbiol,2005.43(6):p.2662-7.
    44.Jacobs M.V.,Snijders P.J.,van den Brule A.J.,et al.,A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings.J Clin Microbiol,1997.35(3):p.791-5.
    45.Gheit T.,Landi S.,Gemignani F.,et al.,Development of a sensitive and specific assay combining multiplex PCR and DNA microarray primer extension to detect high-risk mucosal human papillomavirus types.J Clin Microbiol,2006.44(6):p.2025-31.
    46.Coutlee F.,Provencher D.,and Voyer H.,Detection of human papillomavirus DNA in cervical lavage specimens by a nonisotopic consensus PCR assay.J Clin Microbiol,1995.33(8):p.1973-8.
    47.Cho N.H.,An H.J.,Jeong J.K.,et al.,Genotyping of 22 human papillomavirus types by DNA chip in Korean women:comparison with cytologic diagnosis.Am J Obstet Gynecol,2003.188(1):p.56-62.
    48.Albrecht V.,Chevallier A.,Magnone V.,et al.,Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.J Virol Methods,2006.137(2):p.236-44.
    49.An H.J.,Cho N.H.,Lee S.Y.,et al.,Correlation of cervical carcinoma and precancerous lesions with human papillomavirus(HPV)genotypes detected with the HPV DNA chip microarray method Cancer,2003.97(7):p.1672-80.
    50.Dunbar S.,Godbout R.,Newkirk H.,et al.,Microsphere suspension array technology for SNP detection in cattle.IEEE Eng Med Biol Mag,2003.22(4):p.158-62.
    51.Dunbar S.A.,Vander Zee C.A.,Oliver K.G.,et al.,Quantitative,multiplexed detection of bacterial pathogens:DNA and protein applications of the Luminex LabMAP system.J Microbiol Methods,2003.53(2):p.245-52.
    52.Brink A.A.,Snijders P.J.,and Meijer C.J.,HPV detection methods.Dis Markers,2007.23(4):p.273-81.
    53.Schiffman M.,Herrero R.,Desalle R.,et al.,The carcinogenicity of human papillomavirus types reflects viral evolution.Virology,2005.337(1):p.76-84.
    54.Castle P.E.,Solomon D.,Schiffman M.,et al.,Human papillomavirus type 16infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities.J Natl Cancer Inst,2005.97(14):p.1066-71.
    55.Karlsen F.,Kalantari M.,Jenkins A.,et al.,Use of multiple PCR primer sets for optimal detection of human papillomavirus.J Clin Microbiol,1996.34(9):p.2095-100.
    1.Bosch F.X.,Manos M.M.,Munoz N.,et al.,Prevalence of human papillomavirus in cervical cancer:a worldwide perspective.International biological study on cervical cancer(IBSCC)Study Group.J Natl Cancer Inst,1995.87(11):p.796-802.
    2.Schiffman M.H.,Bauer H.M.,Hoover R.N.,et al.,Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia.J Natl Cancer Inst,1993.85(12):p.958-64.
    3.Bosch EX.,Lorincz A.,Munoz N.,et al.,The causal relation between human papillomavirus and cervical cancer.J Clin Pathol,2002.55(4):p.244-65.
    4.Schiffman M.and Castle P.E.,Human papillomavirus:epidemiology and public health.Arch Pathol Lab Med,2003.127(8):p.930-4.
    5.Schiffman M.and Kjaer S.K.,Chapter 2:Natural history of anogenital human papillomavirus infection and neoplasia.J Natl Cancer Inst Monogr,2003(31):p.14-9.
    6.Liaw K.L.,Glass A.G.,Manos M.M.,et al.,Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.J Natl Cancer Inst,1999.91(11):p.954-60.
    7.Schlecht N.F.,Kulaga S.,Robitaille J.,et al.,Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.Jama,2001.286(24):p.3106-14.
    8.Kjaer S.K.,van den Brule A.J.,Paull G.,et al.,Type specific persistence of high risk human papillomavirus(HPV)as indicator of high grade cervical squamous intraepithelial lesions in young women:population based prospective follow up study.Bmj,2002.325(7364):p.572.
    9.Tjalma W.A.,Arbyn M.,Paavonen J.,et al.,Prophylactic human papillomavirus vaccines:the beginning of the end of cervical cancer.Int J Gynecol Cancer,2004.14(5):p.751-61.
    10.Baseman J.G.and Koutsky L.A.,The epidemiology of human papillomavirus infections.J Clin Virol,2005.32 Suppl 1:p.S16-24.
    11.Brown D.R.,McClowry T.L.,Woods K.,et al.,Nucleotide sequence and characterization of human papillomavirus type 83,a novel genital papillomavirus.Virology,1999.260(1):p.165-72.
    12.Herrero R.,Hildesheim A.,Bratti C.,et al.,Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica.J Natl Cancer Inst,2000.92(6):p.464-74.
    13.Munoz N.,Bosch F.X.,Castellsague X.,et al.,Against which human papillomavirus types shall we vaccinate and screen? The international perspective.Int J Cancer,2004.111(2):p.278-85.
    14.Clifford G.M.,Smith J.S.,Plummer M.,et al.,Human papillomavirus types in invasive cervical cancer worldwide:a meta-analysis.Br J Cancer,2003.88(1):p.63-73.
    15.Clifford G.M.,Smith J.S.,Aguado T.,et al.,Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer." a meta-analysis.Br J Cancer,2003.89(1):p.101-5.
    16.Munoz N.,Bosch F.X.,de Sanjose S.,et al.,Epidemiologic classification of human papillomavirus types associated with cervical cancer.N Engl J Med,2003.348(6):p.518-27.
    17.Einstein M.H.and Goldberg G.L.,Human papillomavirus and cervical neoplasia.Cancer Invest,2002.20(7-8):p.1080-5.
    18.Brink A.A.,Snijders P.J.,and Meijer C.J.,HPV detection methods.Dis Markers,2007.23(4):p.273-81.
    19.Schiffman M.,Herrero R.,Desalle R.,et al.,The carcinogenicity of human papillomavirus types reflects viral evolution.Virology,2005.337(1):p.76-84.
    20.Castle P.E.,Solomon D.,Schiffman M.,et al.,Human papillomavirus type 16infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities.J Natl Cancer Inst,2005.97(14):p.1066-71.
    21.Harper D.M.,Franco E.L.,Wheeler C.M.,et al.,Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18:follow-up from a randomised control trial.Lancet,2006.367(9518):p.1247-55.
    22.Villa L.L.,Costa R.L,,Petta C.A.,et al.,Prophylactic quadrivalent human papillomavirus(types 6,11,16,and 18)L1 virus-like particle vaccine in young women:a randomised double-blind placebo-controUed multicentre phase Ⅱ efficacy trial.Lancet Oncol,2005.6(5):p.271-8.
    23.An H.J.,Cho N.H.,Lee S.Y.,et al.,Correlation of cervical carcinoma and precancerous lesions with human papillomavirus(HPV)genotypes detected with the HPV DNA chip microarray method Cancer,2003.97(7):p.1672-80.
    24.Dai Y.,Huang Y.S.,Tang M.,et al.,Distribution and clinical significance of human papillomavirus subtypes in Shenzhen city,People's Republic of China.Int J Gynecol Cancer,2008.18(2):p.295-9.
    25.Bosch F.X.,Munoz N.,de Sanjose S.,et al.,Risk factors for cervical cancer in Colombia and Spain.Int J Cancer,1992.52(5):p.750-8.
    26.Becker T.M.,Wheeler C.M.,McGough N.S.,et al.,Sexually transmitted diseases and other risk factors for cervical dysplasia among southwestern Hispanic and non-Hispanic white women.Jama,1994.271(15):p.1181-8.
    27.Saslow D.,Runowicz C.D.,Solomon D.,et al.,American Cancer Society guideline for the early detection of cervical neoplasia and cancer.CA Cancer J Clin,2002.52(6):p.342-62.
    28.ACOG Practice Bulletin:clinical management guidelines for obstetrician-gynecologists.Number 45,August 2003.Cervical cytology screening (replaces committee opinion 152,March 1995).Obstet Gynecol,2003.102(2):p.417-27.
    29.Woodman C.B.,Collins S.,Winter H.,et al.,Natural history of cervical human papillomavirus infection in young women:a longitudinal cohort study.Lancet,2001. 357(9271):p.1831-6.
    30.Peto J.,Gilham C.,Deacon J.,et al.,Cervical HPV infection and neoplasia in a large population-based prospective study:the Manchester cohort.Br J Cancer,2004.91(5):p.942-53.
    31.Smith J.S.,Lindsay L.,Hoots B.,et al.,Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions:a meta-analysis update.Int J Cancer,2007.121(3):p.621-32.
    32.Li L.K.,Dai M.,Clifford G.M.,et al.,Human papillomavirus infection in Shenyang City,People's Republic of China:A population-based study.Br J Cancer,2006.95(11):p.1593-7.
    33.Takahashi Y.,Yamade I.,Nakamura T.,et al.,Infection by human papillomavirus types 6,11,16,18,31,33 and 35 of the cervix in Japanese women.Int J Gynecol Cancer,1995.5(1):p.45-48.
    34.Lorincz A.T.,Temple G.F.,Kurman R.J.,et al.,Oncogenic association of specific human papillomavirus types with cervical neoplasia.J Natl Cancer Inst,1987.79(4):p.671-7.
    35.Sowjanya A.P.,Jain M.,Poli U.R.,et al.,Prevalence and distribution of high-risk human papilloma virus(HPV)types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh,India.BMC Infect Dis,2005.5:p.116.
    36.Hammouda D.,Munoz N.,Herrero R.,et al.,Cervical carcinoma in Algiers,Algeria:human papillomavirus and lifestyle risk factors.Int J Cancer,2005.113(3):p.483-9.
    37.Kay P.,Soeters R.,Nevin J.,et al.,High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia.J Med Virol,2003.71(2):p.265-73.
    38.Stanczuk G.A.,Kay P.,Sibanda E.,et al.,Typing of human papillomavirus in Zimbabwean patients with invasive cancer of the uterine cervix.Acta Obstet Gynecol Scand,2003.82(8):p.762-6.
    39.Qiu A.D.,Wu E.Q.,Yu X.H.,et al.,HPV prevalence,E6 sequence variation and physical state of HPV16 isolates from patients with cervical cancer in Sichuan,China.Gynecol Oncol,2007.104(1):p.77-85.
    40.Dai M.,Bao Y.P.,Li N.,et al.,Human papillomavirus infection in Shanxi Province,People's Republic of China:a population-based study.Br J Cancer,2006.95(1):p.96-101.
    41.Wu R.F.,Dai M.,Qiao Y.L.,et al.,Human papillomavirus infection in women in Shenzhen City,People's Republic of China,a population typical of recent Chinese urbanisation.Int J Cancer,2007.121(6):p.1306-11.
    42.Jeng C.J.,Phdl,Ko M.L.,et al.,Prevalence of cervical human papillomavirus in Taiwanese women.Clin Invest Med,2005.28(5):p.261-6.
    43.Lee H.S.,Kim K.M.,Kim S.M.,et al.,Human papillomavirus genotyping using HPV DNA chip analysis in Korean women.Int J Gynecol Cancer,2007.17(2):p.497-501.
    44.Lungu O.,Sun X.W.,Felix J.,et al.,Relationship of human papillomavirus type to grade of cervical intraepithelial neoplasia.Jama,1992.267(18):p.2493-6.
    45.Fife K.H.,Cramer H.M.,Schroeder J.M.,et al.,Detection of multiple human papillomavirus types in the lower genital tract correlates with cervical dysplasia.J Med Virol,2001.64(4):p.550-9.
    46.Ho G.Y.,Palan P.R.,Basu J.,et al.,Viral characteristics of human papillomavirus infection and antioxidant levels as risk factors for cervical dysplasia.Int J Cancer,1998.78(5):p.594-9.
    47.Chaturvedi A.K.,Myers L.,Hammons A.F.,et al.,Prevalence and clustering patterns of human papillomavirus genotypes in multiple infections.Cancer Epidemiol Biomarkers Prev,2005.14(10):p.2439-45.
    48.Morrison E.A.,Ho G.Y.,Vermund S.H.,et al.,Human papillomavirus infection and other risk factors for cervical neoplasia:a case-control study.Int J Cancer,1991.49(1):p.6-13.
    49.Chaouki N.,Bosch F.X.,Munoz N.,et al.,The viral origin of cervical cancer in Rabat,Morocco.Int J Cancer,1998.75(4):p.546-54.
    50.Sasagawa T.,Basha W.,Yamazaki H.,et al.,High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women.Cancer Epidemiol Biomarkers Prev,2001.10(1):p.45-52.
    51.van der Graaf Y.,Molijn A.,Doornewaard H.,et al.,Human papillomavirus and the long-term risk of cervical neoplasia.Am J Epidemiol,2002.156(2):p.158-64.
    52.Herrero R.,Castle P.E.,Schiffman M.,et al.,Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste,Costa Rica.J Infect Dis,2005.191(11):p.1796-807.
    53.Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions:baseline data from a randomized trial.The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study(ALTS)Group.J Natl Cancer Inst,2000.92(5):p.397-402.
    54.Bergeron C.,Ferenczy A.,Shah K.V.,et al.,Multicentric human papillomavirus infections of the female genital tract:correlation of viral types with abnormal mitotic figures,colposcopic presentation,and location.Obstet Gynecol,1987.69(5):p.736-42.
    55.Reid R.,Greenberg M.,Jenson A.B.,et al.,Sexually transmitted papillomaviral infections.I.The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types.Am J Obstet Gynecol,1987.156(1):p.212-22.
    56.Schneider A.,Kraus H.,Schuhmann R.,et al.,Papillomavirus infection of the lower genital tract:detection of viral DNA in gynecological swabs.Int J Cancer,1985.35(4):p.443-8.
    57.Cox J.T.,Lorincz A.T.,Schiffman M.H.,et al.,Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance.Am J Obstet Gynecol,1995. 172(3):p.946-54.
    58.Cuzick J.,Szarewski A.,Terry G.,et al.,Human papillomavirus testing in primary cervical screening.Lancet,1995.345(8964):p.1533-6.
    59.Segal A.,Frost F.A.,Miranda A.,et al.,Predictive value of diagnoses of endocervical glandular abnormalities in cervical smears.Pathology,2003.35(3):p.198-203.
    60.Nobbenhuis M.A.,Meijer C.J.,van den Brule A.J.,et al.,Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia.Br J Cancer,2001.84(6):p.796-801.
    1.Parkin D.M.and Bray F.,Chapter 2:The burden of HPV-related cancers.Vaccine,2006.24 Suppl 3:p.S11-25.
    2.Wang S.S.,Sherman M.E.,Hildesheim A.,et al.,Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000.Cancer,2004.100(5):p.1035-44.
    3.Bray F.,Carstensen B.,Moiler H.,et al.,Incidence trends of adenocarcinoma of the cervix in 13 European countries.Cancer Epidemiol Biomarkers Prey,2005.14(9):p.2191-9.
    4.de Villiers E.M.,Fauquet C.,Broker T.R.,et al.,Classification of papillomaviruses.Virology,2004.324(1):p.17-27.
    5.Collins S.,Mazloomzadeh S.,Winter H.,et al.,High incidence of cervical human papillomavirus infection in women during their first sexual relationship.Bjog,2002.109(1):p.96-8.
    6.Castle P.E.,Schiffman M.,Herrero R.,et al.,A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste,Costa Rica.J Infect Dis,2005.191(11):p.1808-16.
    7.Franceschi S.,Herrero R.,Clifford G.M.,et al.,Variations in the age-specific curves of human papillomavirus prevalence in women worldwide.Int J Cancer,2006.119(11):p.2677-84.
    8.Woodman C.B.,Collins S.,Winter H.,et al.,Natural history of cervical human papillomavirus infection in young women:a longitudinal cohort study.Lancet,2001.357(9271):p.1831-6.
    9.de Sanjose S.,Bosch F.X.,Tafur L.A.,et al.,Clearance of HPV infection in middle aged men and women after 9 years'follow up.Sex Transm Infect,2003.79(4):p.348.
    10.Richardson H.,Kelsall G.,Tellier P.,et al.,The natural history of type-specific human papillomavirus infections in female university students.Cancer Epidemiol Biomarkers Prev,2003.12(6):p.485-90.
    11.Ho G.Y.,Burk R.D.,Klein S.,et al.,Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia.J Natl Cancer Inst,1995.87(18):p.1365-71.
    12.Thomas K.K.,Hughes J.P.,Kuypers J.M.,et al.,Concurrent and sequential acquisition of different genital human papillomarvirus types.J Infect Dis,2000.182(4):p.1097-102.
    13.Liaw K.L.,Hildesheim A.,Burk R.D.,et al.,A prospective study of human papillomavirus(HPV)type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types.J Infect Dis,2001.183(1):p.8-15.
    14.Rousseau M.C.,Pereira J.S.,Prado J.C.,et al.,Cervical coinfection with human papillomavirus(HPV)types as a predictor of acquisition and persistence of HPV infection.J Infect Dis,2001.184(12):p.1508-17.
    15.Ho G.Y.,Studentsov Y.,Hall C.B.,et al.,Risk factors for subsequent cervicovaginal human papillomavirus(HPV)infection and the protective role of antibodies to HPV-16 virus-likeparticles.J Infect Dis,2002.186(6):p.737-42.
    16.Brown D.R.,Shew M.L.,Qadadri B.,et al.,A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women.J Infect Dis,2005.191(2):p.182-92.
    17.Mendez F.,Munoz N.,Posso H.,et al.,Cervical coinfection with human papillomavirus(HPV)types and possible implications for the prevention of cervical cancer by HPV vaccines.J Infect Dis,2005.192(7):p.1158-65.
    18.zur Hausen H.,Papillomaviruses and cancer:from basic studies to clinical application.Nat Rev Cancer,2002.2(5):p.342-50.
    19.Roden R.and Wu T.C.,How will HPV vaccines affect cervical cancer? Nat Rev Cancer,2006.6(10):p.753-63.
    20.Doorbar J.,Molecular biology of human papillomavirus infection and cervical cancer.Clin Sci(Lond),2006.110(5):p.525-41.
    21.Clifford G.M.,Smith J.S.,Plummer M.,et al.,Human papillomavirus types in invasive cervical cancer worldwide:a meta-analysis.Br J Cancer,2003.88(1):p.63-73.
    22.Munoz N.,Bosch F.X.,de Sanjose S.,et al.,Epidemiologic classification of human papillomavirus types associated with cervical cancer.N Engl J Med,2003.348(6):p.518-27.
    23.Koutsky L.A.and Harper D.M.,Chapter 13:Current findings from prophylactic HPV vaccine trials.Vaccine,2006.24 Suppl 3:p.S114-21.
    24.Koutsky L.A.,Holmes K.K.,Critchlow C.W.,et al.,A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.N Engl J Med,1992.327(18):p.1272-8.
    25.Evander M.,Edlund K.,Gustafsson A.,et al.,Human papillomavirus infection is transient in young women:a population-based cohort study.J Infect Dis,1995.171(4):p.1026-30.
    26.Giuliano A.R.,Papenfuss M.,Nour M.,et al.,Antioxidant nutrients:associations with persistent human papillomavirus infection.Cancer Epidemiol Biomarkers Prev,1997.6(11):p.917-23.
    27.Ho G.Y.,Bierman R.,Beardsley L.,et al.,Natural history of cervicovaginal papillomavirus infection inyoung women.N Engl J Med,1998.338(7):p.423-8.
    28.Liaw K.L.,Glass A.G.,Manos M.M.,et al.,Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.J Natl Cancer Inst,1999.91(11):p.954-60.
    29.Nobbenhuis M.A.,Walboomers J.M.,Helmerhorst T.J.,et al.,Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening:a prospective study.Lancet,1999.354(9172):p.20-5.
    30.Wallin K.L.,Wiklund F.,Angstrom T.,et al.,Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer.N Engl J Med,1999.341(22):p.1633-8.
    31.Clavel C.,Masure M.,Levert M.,et al.,Human papillomavirus detection by the hybrid capture Ⅱ assay:a reliable test to select women with normal cervical smears at risk for developing cervical lesions.Diagn Mol Pathol,2000.9(3):p.145-50.
    32.Elfgren K.,Kalantari M.,Moberger B.,et al.,A population-based five-year follow-up study of cervical human papillomavirus infection.Am J Obstet Gynecol,2000.183(3):p.561-7.
    33.Hopman E.H.,Rozendaal L.,Voorhorst F.J.,et al.,High risk human papillomavirus in women with normal cervical cytology prior to the development of abnormal cytology and colposcopy.Bjog,2000.107(5):p.600-4.
    34.Ylitalo N.,Josefsson A.,Melbye M.,et al.,A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in situ.Cancer Res,2000.60(21):p.6027-32.
    35.Ahdieh L.,Klein R.S.,Burk R.,et al.,Prevalence,incidence,and type-specific persistence of human papillomavirus in human immunodeficiency virus (HIV)-positive and HIV-negative women.J Infect Dis,2001.184(6):p.682-90.
    36.Ghaderi M.,Wallin K.L.,Wiklund F.,et al.,Risk of invasive cervical cancer associated withpolymorphic HLA DR/DQ haplotypes.Int J Cancer,2002.100(6):p.698-701.
    37.Kjaer S.K.,van den Brule A.J.,Paull G.,et al.,Type specific persistence of high risk human papillomavirus(HPV)as indicator of high grade cervical squamous intraepithelial lesions in young women:population based prospective follow up study.Bmj,2002.325(7364):p.572.
    38.Sedjo R.L.,Inserra P.,Abrahamsen M.,et al.,Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women.Cancer Epidemiol Biomarkers Prev,2002.11(4):p.353-9.
    39.van der Graaf Y.,Molijn A.,Doornewaard H.,et al.,Human papillomavirus and the long-term risk of cervical neoplasia.Am J Epidemiol,2002.156(2):p.158-64.
    40.van Duin M.,Snijders P.J.,Schrijnemakers H.F.,et al.,Human papillomavirus 16load in normal and abnormal cervical scrapes:an indicator of CIN Ⅱ/Ⅲ and viral clearance.Int J Cancer,2002.98(4):p.590-5.
    41.Chan J.K.,Monk B.J.,Brewer C.,et al.,HPV infection and number of lifetime sexual partners are strong predictors for 'natural' regression of CIN 2 and 3.Br J Cancer,2003.89(6):p.1062-6.
    42.Giuliano A.R.,Siegel E.M.,Roe D.J.,et al.,Dietary intake and risk of persistent human papillomavirus(HPV)infection:the Ludwig-McGill HPV Natural History Study.J Infect Dis,2003.188(10):p.1508-16.
    43.Cuschieri K.S.,Whitley M.J.,and Cubic H.A.,Human papillomavirus type specific DNA and RNA persistence-implications for cervical disease progression and monitoring.J Med Virol,2004.73(1):p.65-70.
    44.Peto J.,Gilham C.,Deacon J.,et al.,Cervical HPV infection and neoplasia in a large population-based prospective study:the Manchester cohort.Br J Cancer,2004.91(5):p.942-53.
    45.Piyathilake C.J.,Henao O.L.,Macaluso M.,et al.,Folate is associated with the natural history of high-risk human papillomaviruses.Cancer Res,2004.64(23):p.8788-93.
    46.Wang S.S.,Trunk M.,Schiffman M.,et al.,Validation of p16INK4a as a marker of oncogenic human papillomavirus infection in cervical biopsies from a population-based cohort in Costa Rica.Cancer Epidemiol Biomarkers Prev,2004.13(8):p.1355-60.
    47.Lillo F.B.,Lodini S.,Ferrari D.,et al.,Determination of human papillomavirus (HPV)load and type in high-grade cervical lesions surgically resected from HIV-infected women during follow-up of HPV infection.Clin Infect Dis,2005.40(3):p.451-7.
    48.Moscicki A.B.,Hills N.,Shiboski S.,et al.,Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.Jama,2001.285(23):p.2995-3002.
    49.Woodman C.B.and Collins S.,A critique of cohort studies examining the role of human papillomavirus infection in cervical neoplasia.Bjog,2002.109(12):p.1311-8.
    50.Winer R.L.,Lee S.K.,Hughes J.P.,et al.,Genital human papillomavirus infection:incidence and risk factors in a cohort of female university students.Am J Epidemiol,2003.157(3):p.218-26.
    51.Hall S.,Lorincz A.,Shah F.,et al.,Human papillomavirus DNA detection in cervical specimens by hybrid capture:correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix.Gynecol Oncol,1996.62(3):p.353-9.
    52.Nindl I.,Greinke C.,Zahm D.M.,et al.,Human papillomavirus distribution in cervical tissues of different morphology as determined by hybrid capture assay and PCR.Int J Gynecol Pathol,1997.16(3):p.197-204.
    53.Ho G.Y.,Palan P.R.,Basu J.,et al.,Viral characteristics of human papillomavirus infection and antioxidant levels as risk factors for cervical dysplasia.Int J Cancer,1998.78(5):p.594-9.
    54.Swan D.C.,Tucker R.A.,Tortolero-Luna G.,et al.,Human papillomavirus(HPV)DNA copy number is dependent on grade of cervical disease and HPV type.J Clin Microbiol,1999.37(4):p.1030-4.
    55.Heard I.,Tassie J.M.,Schmitz V.,et al.,Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1).Obstet Gynecol,2000.96(3):p.403-9.
    56.Crum C.P.,Beach K.J.,Hedley M.L.,et al.,Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia:results from the ZYC101a protocol.J Infect Dis,2004.189(8):p.1348-54.
    57.Cricca M.,Venturoli S.,Morselli-Labate A.M.,et al.,HPV DNA patterns and disease implications in the follow-up of patients treated for HPV16 high-grade carcinoma in situ.J Med Virol,2006.78(4):p.494-500.
    58.Berumen J.,Unger E.R.,Casas L.,et al.,Amplification of human papillomavirus types 16 and 18 in invasive cervical cancer.Hum Pathol,1995.26(6):p.676-81.
    59.Jeon S.,Allen-Hoffmann B.L.,and Lambert P.F.,Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells.J Virol,1995.69(5):p.2989-97.
    60.Spartz H.,Lehr E.,Zhang B.,et al.,Progression from productive infection to integration and oncogenic transformation in human papillomavirus type 59-immortalized foreskin keratinocytes.Virology,2005.336(1):p.11-25.
    61.Sherman M.E.,Wang S.S.,Wheeler C.M.,et al.,Determinants of human papillomavirus load among women with histological cervical intraepithelial neoplasia 3:dominant impact of surrounding low-grade lesions.Cancer Epidemiol Biomarkers Prev,2003.12(10):p.1038-44.
    62.Gravitt P.E.,Burk R.D.,Lorincz A.,et al.,A comparison between real-time polymerase chain reaction and hybrid capture 2 for human papillomavirus DNA quantitation.Cancer Epidemiol Biomarkers Prev,2003.12(6):p.477-84.
    63.Ho C.M.,Yang S.S.,Chien T.Y.,et al.,Detection and quantitation of human papillomavirus type 16,18 and 52 DNA in the peripheral blood of cervical cancer patients.Gynecol Oncol,2005.99(3):p.615-21.
    64.Woodman C.B.,Collins S.,Rollason T.P.,et al.,Human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia.Lancet,2003.361(9351):P.40-3.
    65.Mitchell H.,Medley G.,Gordon I.,et al.,Cervical cytology reported as negative and risk of adenocarcinoma of the cervix:no strong evidence of benefit.Br J Cancer,1995.71(4):p.894-7.
    66.Jeon S.and Lambert P.F.,Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs:implications for cervical carcinogenesis.Proc Natl Acad Sci U S A,1995.92(5):p.1654-8.
    67.Andersson S.,Safari H.,Mints M.,et al.,Type distribution,viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer(CIN).Br J Cancer,2005.92(12):p.2195-200.
    68.Peitsaro P.,Johansson B.,and Syrjanen S.,Integrated humanpapillomavirus type 16is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique.J Clin Microbiol,2002.40(3):p.886-91.
    69.Choo K.B.,Pan C.C.,and Han S.H.,Integration of human papillomavirus type 16into cellular DNA of cervical carcinoma:preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames.Virology,1987.161(1):p.259-61.
    70.Meanwell C.A.,Cox M.F.,Blackledge G.,et al.,HPV 16 DNA in normal and malignant cervical epithelium:implications for the aetiology and behaviour of cervical neoplasia.Lancet,1987.1(8535):p.703-7.
    71.Fuchs P.G.,Girardi F.,and Pfister H.,Human papillomavirus 16 DNA in cervical cancers and in lymph nodes of cervical cancer patients:a diagnostic marker for early metastases? Int J Cancer,1989.43(1):p.41-4.
    72.Matsukura T.,Koi S.,and Sugase M.,Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers.Virology,1989.172(1):p.63-72.
    73.Cooper K.,Herrington C.S.,Graham A.K.,et al.,In situ evidence for HPV16,18,33integration in cervical squamous cell cancer in Britain and South Africa.J Clin Pathol,1991.44(5):p.406-9.
    74.Cullen A.P.,Reid R.,Campion M.,et al.,Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm.J Virol,1991.65(2):p.606-12.
    75.Cooper K.,Herrington C.S.,Lo E.S.,et al.,Integration of human papillomavirus types 16 and 18 in cervical adenocarcinoma.J Clin Pathol,1992.45(5):p.382-4.
    76.Das B.C.,Sharma J.K.,Gopalakrishna V.,et al.,Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions.J Gen Virol,1992.73(Pt 9):p.2327-36.
    77.Chen C.M.,Shyu M.P.,Au L.C.,et al.,Analysis of deletion of the integrated human papillomavirus 16 sequence in cervical cancer:a rapid multiplex polymerase chain reaction approach.J Med Virol,1994.44(2):p.206-11.
    78.Kristiansen E.,Jenkins A.,and Holm R.,Coexistence of episomal and integrated HPV16 DNA in squamous cell carcinoma of the cervix,J Clin Pathol,1994.47(3):p.253-6.
    79.Daniel B.,Mukherjee G.,Seshadri L.,et al.,Changes in the physical state and expression of human papillomavirus type 16 in the progression of cervical intraepithelial neoplasia lesions analysed by PCR.J Gen Virol,1995.76(Pt 10):p.2589-93.
    80.Unger E.R.,Vernon S.D.,Thorns W.W.,et al.,Human papillomavirus and disease-free survival in FIGO stage Ib cervical cancer.J Infect Dis,1995.172(5):p.1184-90.
    81.Park J.S.,Hwang E.S.,Park S.N.,et al.,Physical status and expression of HPV genes in cervical cancers.Gynecol Oncol,1997.65(1):p.121-9.
    82.Pirami L.,Giache V.,and Becciolini A.,Analysis of HP V16,18,31,and 35 DNA in pre-invasive and invasive lesions of the uterine cervix.J Clin Pathol,1997.50(7):p.600-4.
    83.Vernon S.D.,Unger E.R.,Miller D.L.,et al.,Association of human papillomavirus type 16 integration in the E2 gene with poor disease-free survival from cervical cancer.Int J Cancer,1997.74(1):p.50-6.
    84.Kalantari M.,Karlsen F.,Kristensen G.,et al.,Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis.Int J Gynecol Pathol,1998.17(2):p.146-53.
    85.Casas L.,Galvan S.C.,Ordonez R.M.,et al.,Asian-american variants of human papillomavirus type 16 have extensive mutations in the E2 gene and are highly amplified in cervical carcinomas.Int J Cancer,1999.83(4):p.449-55.
    86.Corden S.A.,Sant-Cassia L.J.,Easton A.J.,et al.,The integration of HPV-18 DNA in cervical carcinoma.Mol Pathol,1999.52(5):p.275-82.
    87.Eriksson A.,Herron J.R.,Yamada T.,et al.,Human papillomavirus type 16 variant lineages characterized by nucleotide sequence analysis of the E5 coding segment and the E2 hinge region.J Gen Virol,1999.80(Pt 3):p.595-600.
    88.Kim C.J.,Um S.J.,Hwang E.S.,et al.,The antibody response to HPV proteins and the genomic state of HPVs in patients with cervical cancer.Int J Gynecol Cancer,1999.9(1):p.1-11.
    89.Klaes R.,Woerner S.M.,Ridder R.,et al.,Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integratedpapillomavirus oncogenes.Cancer Res,1999.59(24):p.6132-6.
    90.Yoshinouchi M.,Hongo A.,Nakamura K.,et al.,Analysis by multiplex PCR of the physical status of human papillomavirus type 16 DNA in cervical cancers.J Clin Microbiol,1999.37(11):p.3514-7.
    91.Graham D.A.and Herrington C.S.,HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix:relation to numerical chromosome abnormalities.Mol Pathol,2000.53(4):p.201-6.
    92.Szarka K.,Veress G.,Juhasz A.,et al.,Integration status of virus DNA and p53codon 72 polymorphism in human papillomavirus type 16positive cervical cancers.Anticancer Res,2000.20(3B):p.2161-7.
    93.Giannoudis A.,Duin M.,Snijders P.J.,et al.,Variation in the E2-binding domain of HPV 16 is associated with high-grade squamous intraepithelial lesions of the cervix.Br J Cancer,2001.84(8):p.1058-63.
    94.Tonon S.A.,Picconi M.A.,Bos P.D.,et al.,Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.J Clin Virol,2001.21(2):p.129-34.
    95.Evans M.F.,Mount S.L.,Beatty B.G.,et al.,Biotinyl-tyramide-based in situ hybridization signal patterns distinguish human papillomavirus type and grade of cervical intraepithelial neoplasia.Mod Pathol,2002.15(12):p.1339-47.
    96.Nagao S.,Yoshinouchi M.,Miyagi Y.,et al.,Rapid and sensitive detection of physical status of human papillomavirus type 16 DNA by quantitative real-time PCR.J Clin Microbiol,2002.40(3):p.863-7.
    97.Watts K.J.,Thompson C.H.,Cossart Y.E.,et al.,Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia.Int J Cancer,2002.97(6):p.868-74.
    98.do Horto dos Santos Oliveira L.,Rodrigues Ede V.,de Salles Lopes A.P.,et al.,HPV 16 detection in cervical lesions,physical state of viral DNA and changes in p53 gene.Sao Paulo Med J,2003.121(2):p.67-71.
    99.Gallo G.,Bibbo M.,Bagella L.,et al.,Study of viral integration of HPV-16 in young patients with LSIL.J Clin Pathol,2003.56(7):p.532-6.
    100.Lukaszuk K.,Liss J.,Wozniak I.,et al.,Human papillomavirus type 16 status in cervical carcinoma cell DNA assayed by multiplex PCR.J Clin Microbiol,2003.41(2):p.608-12.
    101.Alazawi W.,Pert M.,Strauss S.,et al.,Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions:associations with lesion grade,state of the HPV16 E2 gene and clinical outcome.Br J Cancer,2004.91(12):p.2063-70.
    102.Hudelist G.,Manavi M.,Pischinger K.I.,et al.,Physical state and expression of HPV DNA in benign and dysplastic cervical tissue:different levels of viral integration are correlated with lesion grade.Gynecol Oncol,2004.92(3):p.873-80.
    103.Sathish N.,Abraham P.,Peedicayil A.,et al.,Human papillomavirus 16 E6/E7transcript and E2 gene status in patients with cervical neoplasia.Mol Diagn,2004.8(1):p.57-64.
    104.Chen Q.Y.,Bian M.L.,Chen Z.H.,et al.,[Detection of integration status of human papillomavirus 16 in cervicalprecancerous lesions].Zhonghua Yi Xue Za Zhi,2005.85(6):p.400-4.
    105.Swan D.C.,Rajeevan M.,Tortolero-Luna G.,et al.,Human papillomavirus type 16E2 and E6/E7 variants.Gynecol Oncol,2005.96(3):p.695-700.
    106.Arias-Pulido H.,Peyton C.L.,Joste N.E.,et al.,Human papillomavirus type 16integration in cervical carcinoma in situ and in invasive cervical cancer..J Clin Microbiol,2006.44(5):p.1755-62.
    107.Bhattacharjee B.and Sengupta S.,HPV16 E2 gene disruption and polymorphisms of E2 and LCR:some significant associations with cervical cancer in lndian women.Gynecol Oncol,2006.100(2):p.372-8.
    108.Bryan J.T.,Taddeo F.,Skulsky D.,et al.,Detection of specific human papillomavirus types in paraffin-embedded sections of cervical carcinomas.J Med Virol,2006.78(1):p.117-24.
    109.Ho C.M.,Chien T.Y.,Huang S.H.,et al.,Integrated human papillomavirus types 52and 58 are infrequently found in cervical cancer,and high viral loads predict risk of cervical cancer.Gynecol Oncol,2006.102(1):p.54-60.
    110.Kulmala S.M.,Syrjanen S.M.,Gyllensten U.B.,et al.,Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology.J Clin Pathol,2006.59(5):p.513-7.
    111.Zheng Y.,Peng Z.L.,Lou J.Y.,et al.,[Detection of physical status of human papillomavirus 16 in cervical cancer tissue and SiHa cell line by multiplex real-time polymerase chain reaction].Ai Zheng,2006.25(3):p.373-7.
    112.Vinokurova S.,Wentzensen N.,Einenkel J.,et al.,Clonal history of papillomavirus-induced dysplasia in the female lower genital tract.J Natl Cancer Inst,2005.97(24):p.1816-21.
    113.Wilke C.M.,Hall B.K.,Hoge A.,et al.,FRA3B extends over a broad region and contains a spontaneous HPV16 integration site:direct evidence for the coincidence of viral integration sites and fragile sites.Hum Mol Genet,1996.5(2):p.187-95.
    114.Thorland E.C.,Myers S.L.,Persing D.H.,et al.,Human papillomavirus type 16integrations in cervical tumors frequently occur in common fragile sites.Cancer Res, 2000.60(21):p.5916-21.
    115.Ferber M.J.,Montoya D.P.,Yu C.,et al.,Integrations of the hepatitis B virus(HBV)and human papillomavirus(HPV)into the human telomerase reverse transcriptase (hTERT)gene in liver and cervical cancers.Oncogene,2003.22(24):p.3813-20.
    116.Ferber M.J.,Thodand E.C.,Brink A.A.,et al.,Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma.Oncogene,2003.22(46):p.7233-42.
    117.Ferber M.J.,Eilers P.,Schuuring E.,et al.,Positioning of cervical carcinoma and Burkitt lymphoma translocation breakpoints with respect to the human papillomavirus integration cluster in FRA8C at 8q24.13.Cancer Genet Cytogenet,2004.154(1):p.1-9.
    118.Thorland E.C.,Myers S.L.,Gostout B.S.,et al.,Common fragile sites are preferential targets for HPV16 integrations in cervical tumors.Oncogene,2003.22(8):p.1225-37.
    119.Yu T.,Ferber M.J.,Cheung T.H.,et al.,The role of viral integration in the development of cervical cancer.Cancer Genet Cytogenet,2005.158(1):p.27-34.
    120.Wentzensen N.,Ridder R.,Klaes R.,et al.,Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions.Oncogene,2002.21(3):p.419-26.
    121.Ziegert C.,Wentzensen N.,Vinokurova S.,et al.,A comprehensive analysis of HPV integration loci in anogenital lesions combining transcript and genome-based amplification techniques.Oncogene,2003.22(25):p.3977-84.
    122.Wentzensen N.,Vinokurova S.,and von Knebel Doeberitz M.,Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract.Cancer Res,2004.64(11):p.3878-84.
    123.Peter M.,Rosty C.,Couturier J.,et al.,MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors.Oncogene,2006. 25(44):p.5985-93.
    124.Melsheimer P.,Vinokurova S.,Wentzensen N.,et al.,DNA aneuploidy and integration of human papillomavirus type 16 e6/e7 oncogenes in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix uteri.Clin Cancer Res,2004.10(9):p.3059-63.
    125.Pett M.R.,Herdman M.T.,Palmer R.D.,et al.,Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response.Proc Natl Acad Sci U S A,2006.103(10):p.3822-7.
    126.Bechtold V.,Beard P.,and Raj K.,Human papillomavirus type 16 E2 protein has no effect on transcription from episomal viral DNA.J Virol,2003.77(3):p.2021-8.
    127.Herdman M.T.,Pett M.R.,Roberts I.,et al.,Interferon-beta treatment of cervical keratinocytes naturally infected with human papillomavirus 16 episomes promotes rapid reduction in episome numbers and emergence of latent integrants.Carcinogenesis,2006.27(11):p.2341-53.
    128.Kjaer S.K.,Munk C.,Winther J.F.,et al.,Acquisition and persistence of human papillomavirus infection in younger men:a prospective follow-up study among Danish soldiers.Cancer Epidemiol Biomarkers Prev,2005.14(6):p.1528-33.
    129.Lajous M.,Mueller N.,Cruz-Valdez A.,et al.,Determinants of prevalence,acquisition,and persistence of human papillomavirus in healthy Mexican military men.Cancer Epidemiol Biomarkers Prev,2005.14(7):p.1710-6.
    130.Giuliano A.R.,Papenfuss M.,Abrahamsen M.,et al.,Differences in factors associated with oncogenic and nononcogenic human papillomavirus infection at the United States-Mexico border.Cancer Epidemiol Biomarkers Prev,2002.11(9):p.930-4.
    131.Rousseau M.C.,Abrahamowicz M.,Villa L.L.,et al.,Predictors of cervical coinfection with multiple human papillomavirus types.Cancer Epidemiol Biomarkers Prey,2003.12(10):p.1029-37.
    132.Weissenborn S.J.,Funke A.M.,Hellmich M.,et al.,Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive women with high-grade cervical lesions are strongly elevated.J Clin Microbiol,2003.41(6):p.2763-7.
    133.Badaracco G.and Venuti A.,Physical status of HPV types 16 and 18 in topographically different areas of genital turnouts and in paired turnout-free mucosa.hat J Oncol,2005.27(1):p.161-7.
    134.Kim K.,Garner-Hamrick P.A.,Fisher C.,et al.,Methylation patterns of papillomavirus DNA,its influence on E2 function,and implications in viral infection.J Virol,2003.77(23):p.12450-9.
    135.Badal S.,Badal V.,Calleja-Macias I.E.,et al.,The human papillomavirus-18 genome is efficiently targeted by cellular DNA methylation.Virology,2004.324(2):p.483-92.
    136.Kalantari M.,Calleja-Macias I.E.,Yewari D.,et al.,Conserved methylation patterns of human papillomavirus type 16 DNA in asymptomatic infection and cervical neoplasia.J Virol,2004.78(23):p.12762-72.
    137.Turan Y.,Kalantari M.,Calleja-Macias I.E.,et al.,Methylation of the human papillomavirus-18 L1 gene:a biomarker of neoplastic progression? Virology,2006.349(1):p.175-83.
    138.Remus R.,Kammer C.,Heller H.,et al.,Insertion of foreign DNA into an established mammalian genome can alter the methylation of cellular DNA sequences.J Virol,1999.73(2):p.1010-22.
    139.Badal V.,Chuang L.S.,Tan E.H.,et al.,CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens:genomie hypomethylation correlates with carcinogenic progression.J Virol,2003.77(11):p.6227-34.
    140.Van Tine B.A.,Kappes J.C.,Banerjee N.S.,et al.,Clonal selection for transcriptionally active viral oncogenes during progression to cancer.J Virol,2004.78(20):p.11172-86.
    141.Esteller M.,Epigenetics provides a new generation of oncogenes and tumour-suppressor genes.Br J Cancer,2006.94(2):p.179-83.
    142.Kang G.H.,Lee S.,Kim W.H.,et al.,Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylatorphenotype-positive gastric carcinoma.Am J Pathol,2002.160(3):p.787-94.
    143.Vo Q.N.,Geradts J.,Gulley M.L.,et al.,Epstein-Barr virus in gastric adenocarcinomas." association with ethnicity and CDKN2A promoter methylation.J Clin Pathol,2002.55(9):p.669-75.
    144.Yang B.,Guo M.,Herman J.G.,et al.,Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma.Am J Pathol,2003.163(3):p.1101-7.
    145.Li X.,Hui A.M.,Sun L.,et al.,p16INK4A hypermethylation is associated with hepatitis virus infection,age,and gender in hepatocellular carcinoma.Clin Cancer Res,2004.10(22):p.7484-9.
    146.Sakuma K.,Chong J.M.,Sudo M.,et al.,High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma.Int J Cancer,2004.112(2):p.273-8.
    147.Sudo M.,Chong J.M.,Sakuma K.,et al.,Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma.Int J Cancer,2004.109(2):p.194-9.
    148.Kim N.R.,Lin Z.,Kim K.R.,et al.,Epstein-Barr virus and p16INK4A methylation in squamous cell carcinoma and precancerous lesions of the cervix uteri.J Korean Med Sci,2005.20(4):p.636-42.
    149.Suzuki M.,Toyooka S.,Shivapurkar N.,et al.,Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection.Oncogene,2005.24(7):p.1302-8.
    150.Chang M.S.,Uozaki H.,Chong J.M.,et al.,CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus.Clin Cancer Res,2006.12(10):p.2995-3002.
    151.Jicai Z.,Zongtao Y.,Jun L.,et al.,Persistent infection of hepatitis B virus is involved in high rate of p16 methylation in hepatocellular carcinoma.Mol Carcinog,2006.45(7):p.530-6.
    152.Katoh H.,Shibata T.,Kokubu A.,et al.,Epigenetic instability and chromosomal instability in hepatocellular carcinoma.Am J Pathol,2006.168(4):p.1375-84.
    153.Kusano M.,Toyota M.,Suzuki H.,et al.,Genetic,epigenetic,and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus.Cancer,2006.106(7):p.1467-79.
    154.O'Nions J.,Brooks L.A.,Sullivan A.,et al.,p73 is over-expressed in vulval cancer principally as the Delta 2 isoform.Br J Cancer,2001.85(10):p.1551-6.
    155.Gasco M.,Bell A.K.,Heath V.,et al.,Epigenetic inactivation of 14-3-3 sigma in oral carcinoma:association with p16(INK4a)silencing and human papillomavirus negativity.Cancer Res,2002.62(7):p.2072-6.
    156.Dong S.M.,Sun D.I.,Benoit N.E.,et al.,Epigenetic inactivation of RASSF1A in head and neck cancer.Clin Cancer Res,2003.9(10 Pt 1):p.3635-40.
    157.Marsit C.J.,MeClean M.D.,Furniss C.S.,et al.,Epigenetic inactivation of the SFRP genes is associated with drinking,smoking and HPV in head and neck squamous cell carcinoma,Int J Cancer,2006.119(8):p.1761-6.
    158.Santin A.D.,Zhan F.,Bignotti E.,et al.,Gene expression profiles ofprimary HPV16-and HPV18-infected early stage cervical cancers and normal cervical epithelium:identification of novel candidate molecular markers for cervical cancer diagnosis and therapy.Virology,2005.331(2):p.269-91.
    159.Wilting S.M.,Snijders P.J.,Meijer G.A.,et al.,Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix.J Pathol,2006.209(2):p.220-30.
    160.Tsai C.N.,Tsai C.L.,Tse K.P.,et al.,The Epstein-Barr virus oncogeneproduct,latent membrane protein 1,induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases.Proc Natl Acad Sci U S A,2002.99(15):p.10084-9.
    161.Etoh T.,Kanai Y.,Ushijima S.,et al.,Increased DNA methyltransferase 1(DNMT1)protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers.Am J Pathol,2004.164(2):p.689-99.
    162.Lee J.O.,Kwun H.J.,Jung J.K.,et al.,Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1.Oncogene,2005.24(44):p.6617-25.
    163.Li H.P.,Leu Y.W.,and Chang Y.S.,Epigenetic changes in virus-associated human cancers.Cell Res,2005.15(4):p.262-71.
    164.Liu J.,Lian Z.,Han S.,et al.,Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma.Oncogene,2006.25(7):p.1008-17.
    165.Burgers W.A.,Blanchon L.,Pradhan S.,et al.,Viral oncoproteins target the DNA methyltransferases.Oncogene,2007.26(11):p.1650-5.
    166.Robertson K.D.,Ait-Si-Ali S.,Yokochi T.,et al.,DNMTlforms a complex with Rb,E2F1 and HDAC1 and represses transcription from E2F-responsive promoters.Nat Genet,2000.25(3):p.338-42.
    167.McCabe M.T.,Davis J.N.,and Day M.L.,Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway.Cancer Res,2005.65(9):p.3624-32.
    168.McCabe M.T.,Low J.A.,Imperiale M.J.,et al.,Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway.Oncogene,2006.25(19):p.2727-35.
    169.Uren A.,Fallen S.,Yuan H.,et al.,Activation of the canonical Wntpathway during genital keratinocyte transformation:a model for cervical cancer progression.Cancer Res,2005.65(14):p.6199-206.
    170.Yukawa K.,Butz K.,Yasui T.,et al.,Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc-1/skn-1a.J Virol,1996.70(1):p.10-6.
    171.Sun S.and Steinberg B.M.,PTEN is a negative regulator of STAT3 activation in human papillomavirus-infected cells.J Gen Virol,2002.83(Pt 7):p.1651-8.
    172.Kamio M.,Yoshida T.,Ogata H.,et al.,SOCS1[corrected]inhibits HPV-E7-mediated transformation by inducing degradation of E7 protein.Oncogene,2004.23(17):p.3107-15.
    173.Liu L.,Zhang J.,Bates S.,et al.,A methylation profile of in vitro immortalized human cell lines.Int J Oncol,2005.26(1):p.275-85.
    174.Gustafson K.S.,Furth E.E.,Heitjan D.E,et al.,DNA methylation profiling of cervical squamous intraepithelial lesions using liquid-based cytology specimens:an approach that utilizes receiver-operating characteristic analysis.Cancer,2004.102(4):p.259-68.
    175.Maliukova A.V.,Loginov V.I.,Khodyrev D.S.,et al.,[Methylation of the putative tumor suppressor gene,RASSF1A,in primary cervical tumors].Mol Biol(Mosk),2004.38(6):p.1005-13.
    1.Lorincz A.T.and Richart R.M.,Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs.Arch Pathol Lab Med,2003.127(8):p.959-68.
    2.Cuzick J.,Szarewski A.,Cubic H.,et al.,Management of women who test positive for high-risk types of human papillomavirus:the HART study.Lancet,2003.362(9399):p.1871-6.
    3.Bais A.G.,Rebolj M.,Snijders P.J.,et al.,Triage using HPV-testing in persistent borderline and mildly dyskaryotic smears:proposal for new guidelines.Int J Cancer,2005.116(1):p.122-9.
    4.Zielinski G.D.,Bais A.G.,Helmerhorst T.J.,et al.,HPV testing and monitoring of women after treatment of CIN 3:review of the literature and recta-analysis.Obstet Gynecol Surv,2004.59(7):p.543-53.
    5.Scheffner M.,Werness B.A.,Huibregtse J.M.,et al.,The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p5 3.Cell,1990.63(6):p.1129-36.
    6.Dyson N.,Howley P.M.,Munger K.,et al.,The human papilloma virus-16 E7oncoprotein is able to bind to the retinoblastoma gene product.Science,1989.243(4893):p.934-7.
    7.Bosch EX.,Lorincz A.,Munoz N.,et al.,The causal relation between human papillomavirus and cervical cancer.J Clin Pathol,2002.55(4):p.244-65.
    8.Munoz N.,Bosch F.X.,de Sanjose S.,et al.,Epidemiologic classification of human papillomavirus types associated with cervical cancer.N Engl J Med,2003.348(6):p.518-27.
    9.de Villiers E.M.,Fauquet C.,Broker T.R.,et al.,Classification ofpapillomaviruses.Virology,2004.324(1):p.17-27.
    10.Werness B.A.,Levine A.J.,and Howley P.M.,Association of human papillomavirus types 16 and 18 E6 proteins with p53.Science,1990.248(4951):p.76-9.
    11.Gage J.R.,Meyers C.,and Wettstein F.O.,The E7 proteins of the nononcogenic human papillomavirus type 6b(HPV-6b)and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties.J Virol,1990.64(2):p.723-30.
    12.Kirii Y.and Matsukura T.,Nucleotide sequence and phylogenetic classification of human papillomavirus type 67.Virus Genes,1998.17(2):p.117-21.
    13.Munoz N.,Bosch F.X.,Castellsague X.,et al.,Against which human papillomavirus types shall we vaccinate and screen? The international perspective.Int J Cancer,2004.111(2):p.278-85.
    14.Schiffman M.,Khan M.J.,Solomon D.,et al.,A study of the impact of adding HPV types to cervical cancer screening and triage tests.J Natl Cancer Inst,2005.97(2):p.147-50.
    15.Galloway D.A.,Papillomavirus vaccines in clinical trials.Lancet Infect Dis,2003.3(8):p.469-75.
    16.Beskow A.H.,Moberg M.,and Gyllensten U.B.,HLA class Ⅱ allele control of HPV load in carcinoma in situ of the cervix uteri.Int J Cancer,2005.117(3):p.510-4.
    17.Beskow A.H.and Gyllensten U.B.,Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri.Int J Cancer,2002.101(6):p.526-31.
    18.Bulkmans N.W.,Bleeker M.C.,Berkhof J.,et al.,Prevalence of types 16 and 33 is increased in high-risk human papillomavirus positive women with cervical intraepithelial neoplasia grade 2 or worse.Int J Cancer,2005.117(2):p.177-81.
    19.Bulk S.,Berkhof J.,Bulkmans N.W.,et al.,Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands.Br J Cancer,2006.94(1):p.171-5.
    20.Khan M.J.,Castle P.E.,Lorincz A.T.,et al.,The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus(HPV)type 16 or 18and the possible utility of type-specific HPV testing in clinical practice.J Natl Cancer Inst,2005.97(14):p.1072-9.
    21.Castle P.E.,Solomon D.,Schiffman M.,et al.,Human papillomavirus type 16infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities.J Natl Cancer Inst,2005.97(14):p.1066-71.
    22.Gravitt P.E.,Peyton C.L.,Apple R.J.,et al.,Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization,reverse line blot detection method.J Clin Microbiol,1998.36(10):p.3020-7.
    23.Tieben L.M.,ter Schegget J.,Minnaar R.P.,et al.,Detection of cutaneous and genital HPV types in clinical samples by PCR using consensus primers.J Virol Methods,1993.42(2-3):p.265-79.
    24.van den Brule A.J.,Pol R.,Fransen-Daalmeijer N.,et al.,GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes.J Clin Microbiol,2002.40(3):p.779-87.
    25.Gregoire L.,Arella M.,Campione-Piccardo J.,et al.,Amplification of human papillomavirus DNA sequences by using conserved primers.J Clin Microbiol,1989.27(12):p.2660-5.
    26.Kleter B.,van Doorn L.J.,Schrauwen L.,et al.,Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus.J Clin Microbiol,1999.37(8):p.2508-17.
    27.Gravitt P.E.,Peyton C.L.,Alessi T.Q.,et al.,Improved amplification of genital human papillomaviruses.J Clin Microbiol,2000.38(1):p.357-61.
    28.Monsonego J.,Bohbot J.M.,Pollini G.,et al.,Performance of the Roche AMPLICOR human papillomavirus(HPV)test in prediction of cervical intraepithelial neoplasia (CIN)in women with abnormal PAP smear.Gynecol Oncol,2005.99(1):p.160-8.
    29.Jacobs M.V.,Snijders P.J.,van den Brule A.J.,et al.,A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings.J Clin Microbiol,1997.35(3):p.791-5.
    30.Kleter B.,van Doorn L.J.,ter Schegget J.,et al.,Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses.Am J Pathol,1998.153(6):p.1731-9.
    31.Cho N.H.,An H.J.,Jeong J.K.,et al.,Genotyping of 22 human papillomavirus types by DNA chip in Korean women:comparison with cytologic diagnosis.Am J Obstet Gynecol,2003.188(1):p.56-62.
    32.Schmitt M.,Bravo I.G.,Snijders P.J.,et al.,Bead-based multiplex genotyping of human papillomaviruses.J Clin Microbiol,2006.44(2):p.504-12.
    33.Jiang H.L.,Zhu H.H.,Zhou L.F.,et al.,Genotyping of human papillomavirus in cervical lesions by L1 consensus PCR and the Luminex xMAP system.J Med Microbiol,2006.55(Pt 6):p.715-20.
    34.Forslund O.,Antonsson A.,Nordin P.,et al.,A broad range of human papillomavirus types detected with a general PCR method suitable for analysis of cutaneous tumours and normal skin.J Gen Virol,1999.80(Pt 9):p.2437-43.
    35.Shamanin V.,Glover M.,Rausch C.,et al.,Specific types of human papillomavirus found in benign proliferations and carcinomas of the skin in immunosuppressed patients.Cancer Res,1994.54(17):p.4610-3.
    36.Lungu O.,Wright T.C.,Jr.,and Silverstein S.,Typing of human papillomaviruses by polymerase chain reaction amplification with L1 consensus primers and RFLP analysis.Mol Cell Probes,1992.6(2):p.145-52.
    37.Szuhai K.,Sandhaus E.,Kolkman-Uljee S.M.,et al.,A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction.Am J Pathol,2001.159(5):p.1651-60.
    38.Walboomers J.M.,Jacobs M.V.,Manos M.M.,et al.,Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.J Pathol,1999.189(1):p.12-9.
    39.Josefsson A.,Livak K.,and Gyllensten U.,Detection and quantitation of human papillomavirus by using the fluorescent 5′ exonuclease assay.J Clin Microbiol,1999. 37(3):p.490-6.
    40.Hesselink A.T.,van den Brule A.J.,Groothuismink Z.M.,et al.,Comparison of three different PCR methods for quantifying human papillomavirus type 16 DNA in cervical scrape specimens.J Clin Microbiol,2005.43(9):p.4868-71.
    41.Moberg M.,Gustavsson I.,and Gyllensten U.,Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer.J Clin Microbiol,2003.41(7):p.3221-8.
    42.Josefsson A.M.,Magnusson P.K.,Ylitalo N.,et al.,Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ:a nested case-control study.Lancet,2000.355(9222):p.2189-93.
    43.Ylitalo N.,Sorensen P.,Josefsson A.M.,et al.,Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ:a nested case-control study.Lancet,2000.355(9222):p.2194-8.
    44.van Duin M.,Snijders P.J.,Schrijnemakers H.F.,et al.,Human papillomavirus 16load in normal and abnormal cervical scrapes:an indicator of CIN Ⅱ/Ⅲ and viral clearance.Int J Cancer,2002.98(4):p.590-5.
    45.Snijders P.J.,Hogewoning C.J.,Hesselink A.T.,et al.,Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16,18,31 and 33-positive women with normal cytology.Int J Cancer,2006.119(5):p.1102-7.
    46.Snijders P.J.,van den Brule A.J.,and Meijer C.J.,The clinical relevance of human papillomavirus testing:relationship between analytical and clinical sensitivity.J Pathol,2003.201(1):p.1-6.
    47.Sotlar K.,Stubner A.,Dierner D.,et al.,Detection of high-risk human papillomavirus E6 and E7 oncogene transcripts in cervical scrapes by nested RT-polymerase chain reaction.J Med Virol,2004.74(1):p.107-16.
    48.Smits H.L.,van Gemen B.,Schukkink R.,et al.,Application of the NASBA nucleic acid amplification method for the detection of human papillomavirus type 16 E6-E7transcripts.J Virol Methods,1995.54(1):p.75-81.
    49.Cuschieri K.S.,Whitley M.J.,and Cubic H.A.,Human papillomavirus type specific DNA and RNA persistence--implications for cervical disease progression and monitoring.J Med Virol,2004.73(1):p.65-70.
    50.Kraus I.,Molden T.,Erno L.E.,et al.,Human papillomavirus oncogenic expression in the dysplastic portio;an investigation of biopsies from 190 cervical cones.Br J Cancer,2004.90(7):p.1407-13.
    51.Molden T.,Kraus I.,Karlsen F.,et al.,Comparison of human papillomavirus messenger RNA and DNA detection:a cross-sectional study of 4,136 women＞30years of age with a 2-year follow-up of high-grade squamous intraepithelial lesion.Cancer Epidemiol Biomarkers Prev,2005.14(2):p.367-72.
    52.Molden T.,Nygard J.F.,Kraus I.,et al.,Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR:A 2-year follow-up of women with ASCUS or LSIL Pap smear.Int J Cancer,2005.114(6):p.973-6.
    53.Molden T.,Kraus I.,Karlsen F.,et al.,Human papillomavirus E6/E7 mRNA expression in women younger than 30 years of age.Gynecol Oncol,2006.100(1):p.95-100.
    54.Klaes R.,Woerner S.M.,Ridder R.,et al.,Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes.Cancer Res,1999.59(24):p.6132-6.
    55.Wentzensen N.,Ridder R.,Klaes R.,et al.,Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions.Oncogene,2002.21(3):p.419-26.
    56.Vinokurova S.,Wentzensen N.,Einenkel J.,et al.,Clonal history of papillomavirus-induced dysplasia in the female lower genital tract.J Natl Cancer Inst,2005.97(24):p.1816-21.
    57.Clavel C.,Masure M.,Putaud I.,et al.,Hybrid capture Ⅱ,a new sensitive test for human papillomavirus detection.Comparison with hybrid capture Ⅰ and PCR results in cervical lesions.J Clin Pathol,1998.51(10):p.737-40.
    58.Castle P.E.,Schiffman M.,Burk R.D.,et al.,Restricted cross-reactivity of hybrid capture 2 with nononcogenic human papillomavirus types.Cancer Epidemiol Biomarkers Prey,2002.11(11):p.1394-9.
    59.Qureshi M.N.,Rudelli R.D.,Tubbs R.R.,et al.,Role of HPV DNA testing in predicting cervical intraepithelial lesions:comparison of HC HPV and ISH HPV.Diagn Cytopathol,2003.29(3):p.149-55.
    60.Hesselink A.T.,van den Brule A.J.,Brink A.A.,et al.,Comparison of hybrid capture 2 with in situ hybridization for the detection of high-risk human papillomavirus in liquid-based cervical samples.Cancer,2004.102(1):p.11-8.
    61.Hopman A.H.,Smedts F.,Dignef W.,et al.,Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities.J Pathol,2004.202(1):p.23-33.
    62.Kerstens H.M.,Poddighe P.J.,and Hanselaar A.G.,A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine.J Histochem Cytochem,1995.43(4):p.347-52.
    63.Impraim C.C.,Saiki R.K.,Erlich H.A.,et al.,Analysis of DNA extracted from formalin-fixed,paraffin-embedded tissues by enzymatic amplification and hybridization with sequence-specific oligonucleotides.Biochem Biophys Res Commun,1987.142(3):p.710-6.
    64.Slebos R.J.,Boerrigter L.,Evers S.G.,et al.,A rapid and simple procedure for the routine detection of ras point mutations in formalin-fixed,paraffin-embedded tissues.Diagn Mol Pathol,1992.1(2):p.136-41.
    65.Mattosinho de Castro Ferraz Mda G.,Nicolau S.M.,Stavale J.N.,et al.,Cervical biopsy-based comparison of a new liquid-based thin-layer preparation with conventional Pap smears.Diagn Cytopathol,2004.30(4):p.220-6.
    66.Taha N.S.,Focchi J.,Ribalta J.C,et al.,Universal Collection Medium(UCM)is as suitable as the Standard Transport Medium(STM)for Hybrid Capture Ⅱ(HC-2) assay.J Clin Virol,2006.36(1):p.32-5.
    67.de Roda Husman A.M.,Snijders P.J.,Stel H.V.,et al.,Processing of long-stored archival cervical smears for human papillomavirus detection by the polymerase chain reaction.Br J Cancer,1995.72(2):p.412-7.
    68.Tarkowski T.A.,Rajeevan M.S.,Lee D.R.,et al.,Improved detection of viral RNA isolated from liquid-based cytology samples.Mol Diagn,2001.6(2):p.125-30.
    69.Lie A.K.,Risberg B.,Borge B.,et al.,DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia.Gynecol Oncol,2005.97(3):p.908-15.
    70.Lewis F.,Maughan N.J.,Smith V.,et al.,Unlocking the archive--gene expression in paraffin-embedded tissue.J Pathol,2001.195(1):p.66-71.
    71.Qureshi M.N.,Bolick D.,Ringer P.J.,et al.,HPV testing in liquid cytology specimens:comparison of analytic sensitivty and specificity for in situ hybridization and chemiluminescent nucleic acid testing.Acta Cytol,2005.49(2):p.120-6.
    72.Vassilakos P.,Petignat P.,Boulvain M.,et al.,Primary screening for cervical cancer precursors by the combined use of liquid-based cytology,computer-assisted cytology and HPV DNA testing.Br J Cancer,2002.86(3):p.382-8.
    73.Davis-Devine S.,Day S.J.,and Freund G.G.,Test performance comparison of inform HPV and hybrid capture 2 high-risk HPV DNA tests using the SurePath liquid-based Pap test as the collection method.Am J Clin Pathol,2005.124(1):p.24-30.
    74.Zielinski G.D.,Rozendaal L.,Voorhorst F.J.,et al.,HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3.Gynecol Oncol,2003.91(1):p.67-73.
    75.Nobbenhuis M.A.,Meijer C.J.,van den Brule A.J.,et al.,Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia.Br J Cancer,2001.84(6):p.796-801.
    76.Hawley-Nelson P.,Vousden K.H.,Hubbert N.L.,et al.,HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes.Embo J,1989.8(12):p. 3905-10.
    77.Choo K.B.,Pan C.C.,and Han S.H.,Integration of human papillomavirus type 16into cellular DNA of cervical carcinoma:preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames.Virology,1987.161(1):p.259-61.
    78.Hesselink A.T.,Bulkmans N.W.,Berkhof J.,et al.,Cross-sectional comparison of an automated hybrid capture 2 assay and the consensus GP5+/6+ PCR method in a population-based cervical screening program.J Clin Microbiol,2006.44(10):p.3680-5.
    79.Rozendaal L.,Westerga J.,van der Linden J.C.,et al.,PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN Ⅲin women with normal cytology and borderline changes.J Clin Pathol,2000.53(8):p.606-11.
    80.Rozendaal L.,Walboomers J.M.,van der Linden J.C.,et al.,PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears.Int J Cancer,1996.68(6):p.766-9.