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.
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site; with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from the Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Enforcement of copyright
The IJMS takes the protection of copyright very seriously.
If the IJMS discovers that you have used its copyright materials in contravention of the license above, the IJMS may bring legal proceedings against you seeking reparation and an injunction to stop you using those materials. You could also be ordered to pay legal costs.
If you become aware of any use of the IJMS' copyright materials that contravenes or may contravene the license above, please report this by email to firstname.lastname@example.org
If you become aware of any material on the website that you believe infringes your or any other person's copyright, please report this by email to email@example.com