© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 9, 690-698,
May 3, 2000
© 2000 Oxford University Press
REVIEW |
Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis
Correspondence to: Harald zur Hausen, M.D., Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (e-mail: zurhausen{at}dkfz-heidelberg.de).
During the past 20 years, several types of human papillomaviruses (HPVs) have been identified that cause specific types of cancers. The etiology of cancer of the cervix has been linked to several types of HPV, with a high preponderance of HPV16. The role of these virus infections has been established 1) by the regular presence of HPV DNA in the respective tumor biopsy specimens, 2) by the demonstration of viral oncogene expression (E6 and E7) in tumor material, 3) by the identification of transforming properties of these genes, 4) by the requirement for E6 and E7 expression for maintaining the malignant phenotype of cervical carcinoma cell lines, 5) by the interaction of viral oncoproteins with growth-regulating host-cell proteins, and 6) by epidemiologic studies pointing to these HPV infections as the major risk factor for cervical cancer development. In addition to cancer of the cervix, a major proportion of anal, perianal, vulvar, and penile cancers appears to be linked to the same HPV infections. In addition, close to 20% of oropharyngeal cancers contain DNA from the same types of HPV. Recent evidence also points to a possible role of other HPV infections in squamous cell carcinomas of the skin. This review covers recent developments in understanding molecular mechanisms of HPV carcinogenesis, mainly discussing functions of viral oncoproteins and the regulation of viral oncogenes by host-cell factors. Modifications in host-cell genes, most likely engaged in the control of HPV gene expression in proliferating cells, emerge as important events in HPV-mediated carcinogenesis.
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R. B. Park and E. J. Androphy Genetic Analysis of High-Risk E6 in Episomal Maintenance of Human Papillomavirus Genomes in Primary Human Keratinocytes J. Virol., October 11, 2002; 76(22): 11359 - 11364. [Abstract] [Full Text] [PDF]
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E. Ringstrom, E. Peters, M. Hasegawa, M. Posner, M. Liu, and K. T. Kelsey Human Papillomavirus Type 16 and Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., October 1, 2002; 8(10): 3187 - 3192. [Abstract] [Full Text] [PDF]
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 A. J. Berger, A. Baege, T. Guillemette, J. Deeds, R. Meyer, G. Disbrow, R. Schlegel, and R. Schlegel Insulin-Like Growth Factor-Binding Protein 3 Expression Increases during Immortalization of Cervical Keratinocytes by Human Papillomavirus Type 16 E6 and E7 Proteins Am. J. Pathol., August 1, 2002; 161(2): 603 - 610. [Abstract] [Full Text] [PDF]
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 R. G. Ziegler, S. J. Weinstein, and T. R. Fears Nutritional and Genetic Inefficiencies in One-Carbon Metabolism and Cervical Cancer Risk J. Nutr., August 1, 2002; 132(8): 2345S - 2349. [Abstract] [Full Text] [PDF]
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D. Spitkovsky, S. P. Hehner, T. G. Hofmann, A. Moller, and M. L. Schmitz The Human Papillomavirus Oncoprotein E7 Attenuates NF-kappa B Activation by Targeting the Ikappa B Kinase Complex J. Biol. Chem., July 5, 2002; 277(28): 25576 - 25582. [Abstract] [Full Text] [PDF]
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R. Franconi, P. Di Bonito, F. Dibello, L. Accardi, A. Muller, A. Cirilli, P. Simeone, M. G. Dona, A. Venuti, and C. Giorgi Plant-derived Human Papillomavirus 16 E7 Oncoprotein Induces Immune Response and Specific Tumor Protection Cancer Res., July 1, 2002; 62(13): 3654 - 3658. [Abstract] [Full Text] [PDF]
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L. M. Nelson, R. C. Rose, and J. Moroianu Nuclear Import Strategies of High Risk HPV16 L1 Major Capsid Protein J. Biol. Chem., June 21, 2002; 277(26): 23958 - 23964. [Abstract] [Full Text] [PDF]
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J. Hu, R. Han, N. M. Cladel, M. D. Pickel, and N. D. Christensen Intracutaneous DNA Vaccination with the E8 Gene of Cottontail Rabbit Papillomavirus Induces Protective Immunity against Virus Challenge in Rabbits J. Virol., June 5, 2002; 76(13): 6453 - 6459. [Abstract] [Full Text] [PDF]
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F X Bosch, A Lorincz, N Munoz, C J L M Meijer, and K V Shah The causal relation between human papillomavirus and cervical cancer J. Clin. Pathol., April 1, 2002; 55(4): 244 - 265. [Abstract] [Full Text] [PDF]
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A. C. Baege, A. Berger, R. Schlegel, T. Veldman, and R. Schlegel Cervical Epithelial Cells Transduced with the Papillomavirus E6/E7 Oncogenes Maintain Stable Levels of Oncoprotein Expression but Exhibit Progressive, Major Increases in hTERT Gene Expression and Telomerase Activity Am. J. Pathol., April 1, 2002; 160(4): 1251 - 1257. [Abstract] [Full Text] [PDF]
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P. Peitsaro, B. Johansson, and S. Syrjanen Integrated Human Papillomavirus Type 16 Is Frequently Found in Cervical Cancer Precursors as Demonstrated by a Novel Quantitative Real-Time PCR Technique J. Clin. Microbiol., March 1, 2002; 40(3): 886 - 891. [Abstract] [Full Text] [PDF]
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A. Bachmann, B. Hanke, R. Zawatzky, U. Soto, J. van Riggelen, H. zur Hausen, and F. Rosl Disturbance of Tumor Necrosis Factor Alpha-Mediated Beta Interferon Signaling in Cervical Carcinoma Cells J. Virol., January 1, 2002; 76(1): 280 - 291. [Abstract] [Full Text] [PDF]
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I. Renard, D. Mezzanzanica, S. Canevari, S. Ferrini, J. Boniver, P. Delvenne, and N. Jacobs Anti-CD3/Anti-Epidermal Growth Factor Receptor-Bispecific Antibody Retargeting of Lymphocytes against Human Neoplastic Keratinocytes in an Autologous Organotypic Culture Model Am. J. Pathol., January 1, 2002; 160(1): 113 - 122. [Abstract] [Full Text] [PDF]
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 R. D'Anna, H. Le Buanec, G. Alessandri, A. Caruso, A. Burny, R. Gallo, J.-F. Zagury, D. Zagury, and P. D'Alessio Selective Activation of Cervical Microvascular Endothelial Cells by Human Papillomavirus 16-E7 Oncoprotein J Natl Cancer Inst, December 19, 2001; 93(24): 1843 - 1851. [Abstract] [Full Text] [PDF]
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 I. H. Frazer, R. D. Kluyver, G. R. Leggatt, H. Yang Guo, L. Dunn, O. White, C. Harris, A. Liem, and P. Lambert Tolerance or Immunity to a Tumor Antigen Expressed in Somatic Cells Can Be Determined by Systemic Proinflammatory Signals at the Time of First Antigen Exposure J. Immunol., December 1, 2001; 167(11): 6180 - 6187. [Abstract] [Full Text] [PDF]
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K. Szuhai, E. Sandhaus, S. M. Kolkman-Uljee, M. Lemaitre, J.-C. Truffert, R. W. Dirks, H. J. Tanke, G. J. Fleuren, E. Schuuring, and A. K. Raap A Novel Strategy for Human Papillomavirus Detection and Genotyping with SybrGreen and Molecular Beacon Polymerase Chain Reaction Am. J. Pathol., November 1, 2001; 159(5): 1651 - 1660. [Abstract] [Full Text] [PDF]
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C. Leder, J. A. Kleinschmidt, C. Wiethe, and M. Muller Enhancement of Capsid Gene Expression: Preparing the Human Papillomavirus Type 16 Major Structural Gene L1 for DNA Vaccination Purposes J. Virol., October 1, 2001; 75(19): 9201 - 9209. [Abstract] [Full Text] [PDF]
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I. Kukimoto and T. Kanda Displacement of YY1 by Differentiation-Specific Transcription Factor hSkn-1a Activates the P670 Promoter of Human Papillomavirus Type 16 J. Virol., October 1, 2001; 75(19): 9302 - 9311. [Abstract] [Full Text] [PDF]
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 P. Corstjens, M. Zuiderwijk, A. Brink, S. Li, H. Feindt, R. S. Niedbala, and H. Tanke Use of Up-Converting Phosphor Reporters in Lateral-Flow Assays to Detect Specific Nucleic Acid Sequences: A Rapid, Sensitive DNA Test to Identify Human Papillomavirus Type 16 Infection Clin. Chem., October 1, 2001; 47(10): 1885 - 1893. [Abstract] [Full Text] [PDF]
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F. Noya, W.-M. Chien, T. R. Broker, and L. T. Chow p21cip1 Degradation in Differentiated Keratinocytes Is Abrogated by Costabilization with Cyclin E Induced by Human Papillomavirus E7 J. Virol., July 1, 2001; 75(13): 6121 - 6134. [Abstract] [Full Text] [PDF]
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S.-J. Lee, Y.-S. Cho, M.-C. Cho, J.-H. Shim, K.-A. Lee, K.-K. Ko, Y. K. Choe, S.-N. Park, T. Hoshino, S. Kim, et al. Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-{{gamma}} Production in Human Peripheral Blood Mononuclear and NK Cells J. Immunol., July 1, 2001; 167(1): 497 - 504. [Abstract] [Full Text] [PDF]
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S. T. Oh, S. Kyo, and L. A. Laimins Telomerase Activation by Human Papillomavirus Type 16 E6 Protein: Induction of Human Telomerase Reverse Transcriptase Expression through Myc and GC-Rich Sp1 Binding Sites J. Virol., June 15, 2001; 75(12): 5559 - 5566. [Abstract] [Full Text]
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 C. Miracco, N. Palummo, D. Lavergne, A. Nyongo, P. Tosi, and E.-M. de Villiers Malignant Melanomas: Search for Human Papillomaviruses Arch Dermatol, June 1, 2001; 137(6): 826 - 827. [Full Text] [PDF]
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M. Giarrè, S. Caldeira, I. Malanchi, F. Ciccolini, M. J. Leão, and M. Tommasino Induction of pRb Degradation by the Human Papillomavirus Type 16 E7 Protein Is Essential To Efficiently Overcome p16INK4a-Imposed G1 Cell Cycle Arrest J. Virol., May 15, 2001; 75(10): 4705 - 4712. [Abstract] [Full Text]
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T. Veldman, I. Horikawa, J. C. Barrett, and R. Schlegel Transcriptional Activation of the Telomerase hTERT Gene by Human Papillomavirus Type 16 E6 Oncoprotein J. Virol., May 1, 2001; 75(9): 4467 - 4472. [Abstract] [Full Text]
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Y. Kawana, K. Kawana, H. Yoshikawa, Y. Taketani, K. Yoshiike, and T. Kanda Human Papillomavirus Type 16 Minor Capsid Protein L2 N-Terminal Region Containing a Common Neutralization Epitope Binds to the Cell Surface and Enters the Cytoplasm J. Virol., March 1, 2001; 75(5): 2331 - 2336. [Abstract] [Full Text]
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F X Bosch, T Rohan, A Schneider, I Frazer, H Pfister, X Castellsague, S de Sanjose, V Moreno, L M Puig-Tintore, P G Smith, et al. Papillomavirus research update: highlights of the Barcelona HPV 2000 international papillomavirus conference J. Clin. Pathol., March 1, 2001; 54(3): 163 - 175. [Abstract] [Full Text] [PDF]
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H. z. Hausen Cervical Carcinoma and Human Papillomavirus: On the Road to Preventing a Major Human Cancer J Natl Cancer Inst, February 21, 2001; 93(4): 252 - 253. [Full Text] [PDF]
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A. Hengstermann, L. K. Linares, A. Ciechanover, N. J. Whitaker, and M. Scheffner Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells PNAS, January 23, 2001; (2001) 31470698. [Abstract] [Full Text]
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