Summary
Most cervical cancers are preventable when the precursor lesions are detected in time. Human papilloma viruses (HPVs) are the main risk factors for cervical cancer development, but there is a high percentage of healthy women infected with HPV that never develop a lesion. Only a small percentage of low-grade dysplasias finally grow out to invasive cancer. Several biomarkers can be used to identify lesions at risk for malignant progression. Overexpression of p16INK4a is induced by the viral oncoprotein E7 and distinguishes dysplastic lesions from benign changes. Integration of human papillomavirus DNA into the host genome is mainly found in high-grade dysplastic lesions and invasive cancers, and points to an increased progression potential.
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References
Ho, G. Y., Bierman, R., Beardsley, L., Chang, C. J., and Burk, R. D. (1998) Natural history of cervicovaginal papillomavirus infection in young women. N. Engl. J. Med. 338, 423–428.
Duensing, S. and Munger, K. (2004) Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int. J. Cancer 109, 157–162.
Mantovani, F. and Banks, L. (2001) The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20, 7874–7887.
Munger, K., Basile, J. R., Duensing, S., et al. (2001) Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene 20, 7888–7898.
Khleif, S. N., DeGregori, J., Yee, C. L., et al. (1996) Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc. Natl. Acad. Sci. USA 93, 4350–4354.
Von Knebel Doeberitz, M. (2002) New markers for cervical dysplasia to visualise the genomic chaos created by aberrant oncogenic papillomavirus infections. Eur. J. Cancer 38, 2229–2242.
Klaes, R., Woerner, S. M., Ridder, R., et al. (1999) Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res. 59, 6132–6136.
Klaes, R., Friedrich, T., Spitkovsky, D., et al. (2001) Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int. J. Cancer 92, 276–284.
Sahebali, S., Depuydt, C. E., Segers, K., et al. (2004) p16INK4a as an adjunct marker in liquid-based cervical cytology. Int. J. Cancer 108, 871–876.
Trunk, M. J., Dallenbach-Hellweg, G.., Ridder, R., et al. Morphological characteristics of p16ink4a positive cells in cervical cytology samples. Acta Cytologica 48, 771–782.
Klaes, R., Benner, A., Friedrich, T., et al. (2002) p16INK4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. Am. J. Surg. Pathol. 26, 1389–1399.
Jeon, S., Allen-Hoffmann, B. L., and Lambert, P. F. (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J. Virol. 69, 2989–2997.
Jeon, S. and Lambert, P. F. (1995) 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. USA 92, 1654–1658.
Melsheimer, P., Vinokurova, S., Wentzensen, N., Bastert, G., and von Knebel Doeberitz, M. (2004) DNA aneuploidy and integration of HPV-16 E6/E7 oncogenes in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix uteri. Clin. Cancer Res. 10,3059–3063.
Wentzensen, N., Vinokurova, S., and von Knebel Doeberitz, M. (2004) Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 64, 3878–3884.
Ziegert, C., Wentzensen, N., Vinokurova, S., et al. (2003) A comprehensive analysis of HPV integration loci in anogenital lesions combining transcript and genome-based amplification techniques. Oncogene 22, 3977–3984.
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Vinokurova, S., Wentzensen, N., Doeberitz, M.v.K. (2005). Analysis of p16INK4a and Integrated HPV Genomes as Progression Markers. In: Davy, C., Doorbar, J. (eds) Human Papillomaviruses. Methods in Molecular Medicine, vol 119. Humana Press. https://doi.org/10.1385/1-59259-982-6:073
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DOI: https://doi.org/10.1385/1-59259-982-6:073
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