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Case Study on Human
PapillomavirusTeresa DominguezLaTasha HardyFrancisca Mata
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25-five-year-old carpenter
Several hyperkeratotic papules (warts) onPalm inside of index finger
Do not change size
Cause only minimal discomfort
Spontaneously disappear after a year
Case Study Overview
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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
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Fig. 1 HPV infecting theepidermis
Fig. 2 More extreme case of common warts.
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Question I
Will this virus infection spread toother 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.
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Question IIAfter its disappearance, is the infection
likely to be completely resolvedor persist in the host?
Immunocompetent persons:
Once infected with a specific HPV type, it is unlikely
Immunosuppressed persons:
Can present with numerous treatment resistant wartsRecurrent infections with same HPV type
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Question IIIWhat viral, cellular, and host conditions regulate
the replication of this virus and other HPV’s?
Question IIIWhat viral, cellular, and host conditions regulate
the replication of this virus and other HPV’s?
• The Virus– icosahedral particle, 72 capsomers– Closed, circular dsDNA
• The Virus– icosahedral particle, 72 capsomers– Closed, circular dsDNA
computer colorized EM image of Papillomavirus
capsid
Genomic organization of HPV-16
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DNA ReplicationDNA Replication– Replicates and assembles in the nucleus– Dependent on:
• transcription is tightly regulated by the differentiation state of the infected epithelial cell
– Replicates and assembles in the nucleus– Dependent on:
• transcription is tightly regulated by the differentiation state of the infected epithelial cell
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DNA ReplicationDNA Replication
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QIV:How would the papilloma type causing this
infection be identified?
QIV:How would the papilloma type causing this
infection be identified?
What is knownWhat is known
Disease HPV type
Common warts 2, 7
Plantar warts 1, 2, 4
Flat cutaneous warts 3, 10
Anogenital warts6, 11, 42, 43, 44, 55 and
others
Genital malignancies16, 18, 31, 33, 35, 39,
45, 51
Epidermodysplasia verruciformis more than 15 types
Focal epithelial hyperplasia (oral) 13, 32
Oral papillomas 6, 7, 11, 16, 32
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Detection MethodsDetection Methods
• Clinical Recognition• PCR and RT-PCR• PCR Cloning and Sequencing• Standard enzyme linked
immunosorbent assay (ELISA)• Histological Analysis
• Clinical Recognition• PCR and RT-PCR• PCR Cloning and Sequencing• Standard enzyme linked
immunosorbent assay (ELISA)• Histological Analysis
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QV: Is it likely that this type of HPV is associated with human cancer?
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
• 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
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Which types of HPV are associated with cancer?Which types of HPV are associated with cancer?
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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)
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)
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oAnal cancer, vulvar cancer, penile cancer, and throat cancer
o3 classified as probable high-risk (HPV-26,53, &66)
o12 classified as “low-risk” (HPV-6,11,40,42,43,44,54,61,70,72,81, &CP6108)
HPV and Cancer
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HPV- Induced CancersHPV- Induced Cancers
http://HPV_tree_1.png
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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 2007Desante, C., and Demeret, C. Control of papillomavirus DNA replication and transcription. Seminars in Cancer
Biology, 1996: (51): 339–347Kari, 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;6:14Lambert, 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):537-539McBride 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):427-8Reddout, 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):21Stanley, 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):12-9Werness 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_papillomavirushttp://www.gsbs.utmb.edu/microbook/ch066.htmhttp://www.healthscout.com/ency/68/384/main.htmlhttp://www.medicinenet.com/genital_warts_in_women/article.htmhttp://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=131&id=9531http://www.oralcancerfoundation.org/facts/humanpapillomavirus.htm
References
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THANK YOU!