The Role of the Human Papillomavirus (HPV) in Cervical Cancer: A Review about HPV-Induced Carcinogenesis and Its Epidemiology, Diagnosis, Management and Prevention
The human papillomavirus (HPV) was the first virus known to induce carcinogenesis and is associated with cancers of the uterine cervix, anogenital tumors and malignancies of the head and neck. This paper reviews the structure and basic genomic characteristics of the virus and outlines the clinical involvement of the main HPV serotypes, focusing on the carcinogenic role of HPV-16 and 18. The mechanisms that occur in the development of cervical neoplasia due to the oncogenic proteins E6 and E7 which interfere with the regulation of the cell cycle through their interaction with p53 and retinoblastoma protein are described. Epidemiological factors, diagnostic tools and the management of the disease are also reviewed, along with the available vaccines to prevent the viral infection. Insights on current research on involvement of oxidative stress and micro-RNAs in cervical carcinogenesis are also explored as they may unlock new means of diagnosis and treatment in the future.
2. Cubie HA, Cuschieri KS, Tong CYW. Papillomaviruses and polyomaviruses. In: Greenwood D, Barer M, Slack R, Irving W, eds. Medical microbiology. 18th ed. United Kingdom: Churchill Livingstone Elsevier; 2012.
3. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. United Kingdom: World Health Organization, Inter¬national Agency for Research on Cancer; 1995.
4. Howley PM. Warts, cancer and ubiquitylation: lessons from the papillo¬maviruses. Trans Am Clin Climatol Assoc. 2006;117:113-26; discussion 126-7.
5. Blundell R, Camilleri G. The human papillomaviruses (HPVs) and HPV DNA testing. In: Blundell R, ed. Infertility. Saarbrücken (Germany): Lambert Acade¬mic Publishing; 2013. p. 57-82.
6. Dunne EF, Markowitz LE. Genital human papillomavirus infection. Clin In¬fect Dis. 2006 Sep 1;43(5):624-9.
7. Cason J, Rice P, Best JM. Transmission of cervical cancer-associated human papilloma viruses from mother to child. Intervirology. 1998;41(4-5):213-8.
8. Ferenczy A, Wright TC. Anatomy and histology of the cervix. In: Blaustein A, Kurman RJ, ed. Blaustein's pathology of the female genital tract. USA: Springer; 2002. p. 207-24.
9. Narisawa-Saito M, Kiyono T. Basic mechanisms of high-risk human papi¬llomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci. 2007 Oct;98(10):1505-11.
10. Munger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M, et al. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 2001 Nov 26;20(54):7888-98.
11. Blundell R, Camilleri G. The mechanisms of HPV-induced carcinogenesis and the HPV vaccine. In: Blundell R, ed. Infertility. Saarbrücken (Germany): Lambert Academic Publishing; 2013. p. 83-100.
12. Shackelford RE, Kaufmann WK, Paules RS. Cell cycle control, checkpoint mechanisms, and genotoxic stress. Environ Health Perspect. 1999 Feb;107 Suppl 1:5-24.
13. De Marco F. Oxidative stress and HPV carcinogenesis. Viruses. 2013 Feb 12;5(2):708-31.
14. Gomez-Gomez Y, Organista-Nava J, Gariglio P. Deregulation of the miRNAs expression in cervical cancer: human papillomavirus implications. Biomed Res Int. 2013;2013:407052.
15. Martin-Hirsch PL, Wood NJ. Cervical cancer. BMJ Clin Evid. 2011 Jul 27;2011: 0818.
16. Dawar M, Deeks S, Dobson S. Human papillomavirus vaccines launch a new era in cervical cancer prevention. CMAJ. 2007 Aug 28;177(5):456-61.
17. Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and ce¬llular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013;2013:519619.
18. Duenas-Gonzalez A, Serrano-Olvera A, Cetina L, Coronel J. New molecular targets against cervical cancer. Int J Womens Health. 2014 Dec 5;6:1023-31.
19. Scatchard K, Forrest JL, Flubacher M, Cornes P, Williams C. Chemotherapy for metastatic and recurrent cervical cancer. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006469.
20. Candelaria M, Arias-Bonfill D, Chavez-Blanco A, Chanona J, Cantu D, Perez C, et al. Lack in efficacy for imatinib mesylate as second-line treatment of recurrent or metastatic cervical cancer expressing platelet-derived growth factor receptor alpha. Int J Gynecol Cancer. 2009 Dec;19(9):1632-7.
21. Duenas-Gonzalez A, Lizano M, Candelaria M, Cetina L, Arce C, Cervera E. Epigenetics of cervical cancer. An overview and therapeutic perspectives. Mol Cancer. 2005 Oct 25;4:38.
22. Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43.
23. Fau CC, Chandra AF, Febo-Vazquez I. Sexual behavior, sexual attraction, and sexual orientation among adults aged 18-44 in the United States: data from the 2011-2013 National Survey of Family Growth. National Health Statis¬tics Reports JID - 101479519 0115.
24. Geipert N. Vaccinating men for HPV: new strategy for preventing cervical cancer in women? J Natl Cancer Inst. 2005 May 4;97(9):630-1.
25. Katz IT, Wright AA. Preventing cervical cancer in the developing world. N Engl J Med. 2006 Mar 16;354(11):1110.
26. Mello CF. Vaccination against human papillomavirus. Einstein (Sao Paulo). 2013 Dec;11(4):547-9.
27. Schiller JT, Castellsague X, Garland SM. A review of clinical trials of hu¬man papillomavirus prophylactic vaccines. Vaccine. 2012 Nov 20;30 Suppl 5:F123-38.
28. Kitchener H, Almonte M, Wheeler P, Desai M, Gilham C, Bailey A et al. HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial. Br J Cancer. 2006;95(1):56-61.
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