Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis
TLDR
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.Abstract:
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.read more
Citations
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Journal ArticleDOI
Papillomaviruses and cancer: from basic studies to clinical application
TL;DR: Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago and DNA of specific HPV types has since been found in almost all cervical cancer biopsies.
Journal ArticleDOI
The causal relation between human papillomavirus and cervical cancer
TL;DR: It is the right time for medical societies and public health regulators to consider the causal role of human papillomavirus infections in cervical cancer and to define its preventive and clinical implications.
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The 2001 Bethesda System: terminology for reporting results of cervical cytology.
Diane Solomon,Diane D. Davey,Robert J. Kurman,Marianne U. Prey,Stephen S. Raab,Mark E. Sherman,David C. Wilbur,Nancy A. Young +7 more
TL;DR: The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology.
Journal ArticleDOI
The epidemiology of genital human papillomavirus infection.
Helen Trottier,Eduardo L. Franco +1 more
TL;DR: Persistent infection with HR-HPVs is now unequivocally established as a necessary cause of cervical cancer and is likely to be responsible for a substantial proportion of other anogenital neoplasms and upper aero-digestive tract cancers.
Journal ArticleDOI
Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri
Ruediger Klaes,Tibor Friedrich,Dimitry Spitkovsky,Ruediger Ridder,Wolfgang Rudy,Ulrich Petry,Gisela Dallenbach-Hellweg,Dietmar Schmidt,Magnus von Knebel Doeberitz +8 more
TL;DR: Data demonstrate that p16INK4a is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears and that Dysplastic cells could also be identified in cervicalsmears using a specific p16ink4a monoclonal antibody.
References
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The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product
TL;DR: The results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.
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TL;DR: This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein, providing further evidence that the human papillomaviruses, the adenovirus type 5, and SV40 may effect similar cellular pathways in transformation.
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The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
TL;DR: The purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of p53 are reported, and E 6-AP appears to have ubiquitin-protein ligase activity in the absence of E6.
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Structure and transcription of human papillomavirus sequences in cervical carcinoma cells
Elisabeth Schwarz,U K Freese,Lutz Gissmann,Wolfgang Mayer,Birgit Roggenbuck,Armin Stremlau,Harald zur Hausen +6 more
TL;DR: It is found that the HPV 18 DNA is integrated into the cellular genome and is amplified in HeLa and 756 cells, and some of the transcripts are composed of HPV 18 and cellular sequences.
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Papillomavirus infections — a major cause of human cancers
TL;DR: Reports on the presence of HPV infections in cancers of the oral cavity, the larynx, and the esophagus further emphasize the importance of this virus group as proven and suspected human carcinogens.