© 2002 Journal of Clinical Pathology
REVIEW
The causal relation between human papillomavirus and cervical cancer
1 Institut Català d'Oncologia, Servei d'Epidemiologia i Registre del Càncer, Gran Via Km 2.7 s/n 08907 L'Hospitalet de Llobregat, 08907 Barcelona, Spain
2 Digene Corporation, 1201 Clopper Road, Gaithersburg, MD 20878, USA
3 International Agency for Research on Cancer (IARC), Unit of Field and Intervention Studies, 150 Cours Albert-Thomas, F-69372 Lyon, Cedex 08, France
4 Vrije Universiteit Medical Center, Department of Pathology, De Boelelaan 1117, PO Box 70571007, 1081 HV Amsterdam, The Netherlands
5 The John Hopkins School of Public Health, Department of Molecular Microbiology and Immunology, 615 North Wolfe Street, Baltimore, MD 21205, USA
Correspondence to:
Correspondence to:
Dr F X Bosch, Epidemiology and Cancer Registry Unit (SERC), Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Gran Via km 2,7, L'Hospitalet de Llobregat, 08907 Barcelona, Spain;
x.bosch{at}ico.scs.es
The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
Keywords: human papillomavirus; cervical cancer; causality; review
Abbreviations: AF, attributable fraction; ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN, cervical intraepithelial neoplasia; EBV, Epstein-Barr virus; GP, general primer; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HPV, human papillomavirus; HSIL, high grade squamous intraepithelial lesion; HSV-2; type 2 herpes simplex virus; IARC, International Agency for Research on Cancer; IBSCC, international biological study on cervical cancer; OC, oral contraceptive; OR, odds ratio; ORF, open reading frame; Pap, Papanicolaou; PF, protective fraction; PCR, polymerase chain reaction; RB, retinoblastoma; RR, relative risk; STD, sexually transmitted disease; Th1, T helper cell type 1
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Smits, P. H. M., Bakker, R., Jong, E., Mulder, J. W., Meenhorst, P. L., Kleter, B., van Doorn, L.-J., Quint, W. G. V.
(2005). High Prevalence of Human Papillomavirus Infections in Urine Samples from Human Immunodeficiency Virus-Infected Men. J. Clin. Microbiol.
43: 5936-5939
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Fiedler, M., Ressler, S., Campo-Fernandez, B., Laich, A., Jansen, L., Widschwendter, A., Viertler, H.-P., Bacher, N., Morandell, D., Muller-Holzner, E., Durst, M., Jansen-Durr, P., Zwerschke, W.
(2005). Expression of the high-risk human papillomavirus type 18 and 45 E7 oncoproteins in cervical carcinoma biopsies. J. Gen. Virol.
86: 3235-3241
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Lowndes, C. M, Gill, O N.
(2005). Cervical cancer, human papillomavirus, and vaccination. BMJ
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Hesselink, A. T., van den Brule, A. J. C., Groothuismink, Z. M. A., Molano, M., Berkhof, J., Meijer, C. J. L. M., Snijders, P. J. F.
(2005). Comparison of Three Different PCR Methods for Quantifying Human Papillomavirus Type 16 DNA in Cervical Scrape Specimens. J. Clin. Microbiol.
43: 4868-4871
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De la Cruz-Hernandez, E., Garcia-Carranca, A., Mohar-Betancourt, A., Duenas-Gonzalez, A., Contreras-Paredes, A., Perez-Cardenas, E., Herrera-Goepfert, R., Lizano-Soberon, M.
(2005). Differential splicing of E6 within human papillomavirus type 18 variants and functional consequences. J. Gen. Virol.
86: 2459-2468
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Bray, F., Carstensen, B., Moller, H., Zappa, M., Zakelj, M. P., Lawrence, G., Hakama, M., Weiderpass, E.
(2005). Incidence Trends of Adenocarcinoma of the Cervix in 13 European Countries. Cancer Epidemiol. Biomarkers Prev.
14: 2191-2199
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Fontaine, J., Gravitt, P., Duh, L.-M., Lefevre, J., Pourreaux, K., Hankins, C., Coutlee, F., The Canadian Women's HIV Study Group,
(2005). High Level of Correlation of Human Papillomavirus-16 DNA Viral Load Estimates Generated by Three Real-time PCR Assays Applied on Genital Specimens. Cancer Epidemiol. Biomarkers Prev.
14: 2200-2207
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Dias, D., Van Doren, J., Schlottmann, S., Kelly, S., Puchalski, D., Ruiz, W., Boerckel, P., Kessler, J., Antonello, J. M., Green, T., Brown, M., Smith, J., Chirmule, N., Barr, E., Jansen, K. U., Esser, M. T.
(2005). Optimization and Validation of a Multiplexed Luminex Assay To Quantify Antibodies to Neutralizing Epitopes on Human Papillomaviruses 6, 11, 16, and 18. CVI
12: 959-969
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Cao, B., Tian, X., Li, Y., Jiang, P., Ning, T., Xing, H., Zhao, Y., Zhang, C., Shi, X., Chen, D., Shen, Y., Ke, Y.
(2005). LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. Carcinogenesis
26: 1280-1284
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Bossis, I., Roden, R. B. S., Gambhira, R., Yang, R., Tagaya, M., Howley, P. M., Meneses, P. I.
(2005). Interaction of tSNARE Syntaxin 18 with the Papillomavirus Minor Capsid Protein Mediates Infection. J. Virol.
79: 6723-6731
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Poland, G. A., Jacobson, R. M., Koutsky, L. A., Tamms, G. M., Railkar, R., Smith, J. F., Bryan, J. T., Cavanaugh, P. F. Jr, Jansen, K. U., Barr, E.
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80: 601-610
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Tsezou, A., Oikonomou, P., Kollia, P., Mademtzis, I., Kostopoulou, E., Messinis, I., Vamvakopoulos, N.
(2005). The Role of Human Telomerase Catalytic Subunit mRNA Expression in Cervical Dysplasias. Exp. Biol. Med.
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Aldrich, T, Becker, D, Garcia, S G, Lara, D
(2005). Mexican physicians' knowledge and attitudes about the human papillomavirus and cervical cancer: a national survey. Sex. Transm. Infect.
81: 135-141
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Berg, M., DiFatta, J., Hoiczyk, E., Schlegel, R., Ketner, G.
(2005). Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit. Proc. Natl. Acad. Sci. USA
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Bray, F., Loos, A. H., McCarron, P., Weiderpass, E., Arbyn, M., Moller, H., Hakama, M., Parkin, D. M.
(2005). Trends in Cervical Squamous Cell Carcinoma Incidence in 13 European Countries: Changing Risk and the Effects of Screening. Cancer Epidemiol. Biomarkers Prev.
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Parkin, D. M., Bray, F., Ferlay, J., Pisani, P.
(2005). Global Cancer Statistics, 2002. CA Cancer J Clin
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Molden, T., Kraus, I., Karlsen, F., Skomedal, H., Nygard, J. F., Hagmar, B.
(2005). Comparison of Human Papillomavirus Messenger RNA and DNA Detection: A Cross-sectional Study of 4,136 Women >30 Years of Age with a 2-Year Follow-up of High-Grade Squamous Intraepithelial Lesion. Cancer Epidemiol. Biomarkers Prev.
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Youshya, S, Purdie, K, Breuer, J, Proby, C, Sheaf, M T, Oliver, R T D, Baithun, S
(2005). Does human papillomavirus play a role in the development of bladder transitional cell carcinoma? A comparison of PCR and immunohistochemical analysis. J. Clin. Pathol.
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Carrilho, C, Cirnes, L, Alberto, M, Buane, L, Mendes, N, David, L
(2005). Distribution of HPV infection and tumour markers in cervical intraepithelial neoplasia from cone biopsies of Mozambican women. J. Clin. Pathol.
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Baud, D., Ponci, F., Bobst, M., De Grandi, P., Nardelli-Haefliger, D.
(2004). Improved Efficiency of a Salmonella-Based Vaccine against Human Papillomavirus Type 16 Virus-Like Particles Achieved by Using a Codon-Optimized Version of L1. J. Virol.
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Shields, T. S., Brinton, L. A., Burk, R. D., Wang, S. S., Weinstein, S. J., Ziegler, R. G., Studentsov, Y. Y., McAdams, M., Schiffman, M.
(2004). A Case-Control Study of Risk Factors for Invasive Cervical Cancer among U.S. Women Exposed to Oncogenic Types of Human Papillomavirus. Cancer Epidemiol. Biomarkers Prev.
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Anhang, R., Goodman, A., Goldie, S. J.
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