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Case Study on Human Papillomavirus Teresa Dominguez LaTasha Hardy Francisca Mata Case Study Overview 25-five-year-old carpenter Several hyperkeratotic papules (warts) on Palm inside of index finger Do not change size Cause only minimal discomfort Spontaneously disappear after a year What are Warts? Non-cancerous skin growths in the epidermis Caused mostly by HPV-1, 2 and 4 Usually skin-colored and feel rough to the touch Several types: Common warts Foot (planar) warts Flat warts Fig. 1 HPV infecting the epidermis Fig. 2 More extreme case of common warts. Question I Will this virus infection spread to other body parts? Transmission via contact Infection of basal cells of epidermis Breach in the skin predisposing factor There is a possibility of spreading warts to other parts of your body through breaks in the skin. Question II After its disappearance, is the infection likely to be completely resolved or persist in the host? Immunocompetent persons: Once infected with a specific HPV type, it is unlikely Immunosuppressed persons: Can present with numerous treatment resistant warts Recurrent infections with same HPV type Question III What viral, cellular, and host conditions regulate the replication of this virus and other HPV’s? • The Virus – icosahedral particle, 72 capsomers – Closed, circular dsDNA computer colorized EM image of Papillomavirus capsid Genomic organization of HPV-16 – Replicates and assembles in the nucleus – Dependent on: DNA Replication • transcription is tightly regulated by the differentiation state of the infected epithelial cell DNA Replication QIV: How would the papilloma type causing this infection be identified? What is known Disease HPV type Common warts 2, 7 Plantar warts 1, 2, 4 Flat cutaneous warts 3, 10 Anogenital warts 6, 11, 42, 43, 44, 55 and others Genital malignancies 16, 18, 31, 33, 35, 39, 45, 51 Epidermodysplasia verruciformis more than 15 types Focal epithelial hyperplasia (oral) Oral papillomas 13, 32 6, 7, 11, 16, 32 Detection Methods • • • • Clinical Recognition PCR and RT-PCR PCR Cloning and Sequencing Standard enzyme linked immunosorbent assay (ELISA) • Histological Analysis QV: Is it likely that this type of HPV is associated with human cancer? • This type of HPV is not associated with human cancer • HPV-2 (hand warts) • Common skin wart • Does not cause genital warts • Not associated with development of cancer Which types of HPV are associated with cancer? 15 classified as “high-risk” HPV Strains: o 16,18,31,33,35,39,45,51,52,56,58,59,68,73, &82 o 16 & 18 cause 70% of cervical cancers o 2 types of cervical cancer (squamous cell cancer and adenocarcinoma) HPV and Cancer oAnal cancer, vulvar cancer, penile cancer, and throat cancer o3 classified as probable high-risk (HPV-26,53, &66) o12 classified as “low-risk” (HPV6,11,40,42,43,44,54,61,70,72,81, &CP6108) HPV- Induced Cancers http://HPV_tree_1.png References Antonsson, A, et.al. The Ubiquity and Impressive Genomic Diversity of Human Skin Papillomaviruses Suggest a Commensalic Nature of These Viruses. J. Virol. 2000. Vol. (74) Centers for Disease Control and Prevention. 2007 Human Papillomavirus: HPV Information for Clinicians (Brochure). Washington, DC. April 2007 Desante, C., and Demeret, C. Control of papillomavirus DNA replication and transcription. Seminars in Cancer Biology, 1996: (51): 339–347 Kari, I. et. al. Antisense RNA directed to the human papillomavirus type 16 E7 mRNA from herpes simplex virus type 1 derived vectors is expressed in CaSki cells and downregulates E7 mRNA. J. Virol. 2007, 4:47 Kingsley K, Johnson D, O’Malley, S. Transfection of oral squamous cell carcinoma with human papillomavirus-16 induces proliferative and morphological changes in vitro. Cancer Cell Int. 2006 May 22;6:14 Lambert, P. Papillomavirus Replication. J. Virol. 1991, (65):3417-3420. Lehtinen, M. Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. BMJ 1996;(312):537-539 McBride AA, Romanczuk H, Howley PM. The Papillomavirus E2 Regulatory Proteins. J Biol Chem 1991 Oct. 266(28); 18411-18414 Mino T, Mori T, Aoyama Y, Sera T. Development of protein-based antiviral drugs for human papillomaviruses. Nucleic Acids Symp Ser (Oxf). 2007; (51):427-8 Reddout, N. et. al. High Risk HPV types 18 and 16 are potent modulators of oral squamous cell carcinoma phenotypes in vitro. Infect Agent Cancer. 2007 Nov. 14;2(1):21 Stanley, MA. et. al. HPV: From infection to cancer. Biochem Soc Trans. 2007 Dec;35(Pt 6): 1456-60. Walboomers, JM, Jacobs MV, Manos MM, et. al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathology. 1999 Oct. 189(1):12-9 Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990 Apr 6; 248(4951):76-9. http://en.wikipedia.org/wiki/Human_papillomavirus http://www.gsbs.utmb.edu/microbook/ch066.htm http://www.healthscout.com/ency/68/384/main.html http://www.medicinenet.com/genital_warts_in_women/article.htm http://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=131&id=9531 http://www.oralcancerfoundation.org/facts/humanpapillomavirus.htm THANK YOU!