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31 Cards in this Set
- Front
- Back
Structure of HPV
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Circular dsDNA, icosahedral, non-structural proteins with viral DNA replication, cause condylomas, 15 high risk serotypes
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Family name for HPV
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Papillomaviruses (close to polyomaviruses)
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Classification of HPV
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>100 serotypes, 16 and 18 are high risk for cervical carcinoma
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HPV gene expression
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early promoter drives expression of genes for viral DNA replication
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Replication cycle
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Linked to differentiation state of epithelial layer
-virus has to gain entry so basal daughter cells will contain episomal DNA |
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What regulates vegetative DNA replication?
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E2/E1 heterodimer (helps unwind origin of replication)
E2/E2 homodimer (binds and negatively regulates early E6 and E7 promoters, build up E6 and E7 potential) |
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Where do structural proteins collect with HPV?
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Upper layers of epidermis
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Clinical manifestations of HPV
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incubation of 2-6 mo (have to establish genomes in basal layer)
epithelial dysplasia (common warts on hands/feet) condylomas (on mucosal epithelium, usually flat, non-fluid filled, usually regress, prolonged acute infection) |
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ID of condylomas
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on mucosal epithelium, usually flat, non-fluid filled, usually regress, prolonged acute infection
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Persistence of keratinocyte nucleus as cells rise in stratum corneum, keeps in state for DNA replication
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Parakeratosis
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Hypertrophy of stratum corneum
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hyperkeratosis
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Squamous cells with enlarged nuclei and perinuclear clearing in upper and middle layers of epithelium
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koilocytes
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Single or clusters of slightly raised papules, 50-90% resolve within 1-5 yrs
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cutaneous warts
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Autosomal recessive disease with heightened susceptibility to HPV, can lead to invasive SCC
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Epidermodysplasia verruciformis
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Hyperkeratotic papules present in genital area
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anogenital warts
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Most common laryngeal neoplasm in children; papillomas common on vocal cords
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recurrent respiratory papillomatosis
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Transmission of HPV
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direct contact with lesions or surfaces harboring virus (have to have break in the skin)
incredibly common (75% have had >1 infection) |
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Clinical features of cervical cancer
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discharge and abnormal vaginal bleeding, detect with Pap smear and follow up biopsy
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2 cancer types causing cervical cancer by HPV
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SCC (about 80-85%) + adenocarcinoma (15%, originating in glandular tissue)
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CIN1,2,3
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cervical intraepithelial neoplasia
1: lower 1/3 2: basal 2/3 3: full thickness |
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At what stage is viral DNA integrated into the host?
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CIN 3
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Initiating step of HPV oncogenesis
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Rare integration of viral DNA into host chromosome
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Role of E7
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Increases leads to loss of cell cycle regulation
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Role of E6
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Blocks apoptosis
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Two main proteins driving uncontrolled growth of HPV lesions/oncogenic transformation
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E6 and E7
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Synergy between E6 and E7 for SCC
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E7 drives differentiation, E6 blocks apoptosis through p53, both combine to unchecked growth, no p53 to check tumor cells
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HPV16 is frequently associated with what non-cervical cancer?
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Oral SCCC, 20% are HPV associatedl 21% contained both EBV and HPV DNA
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Dx of HPV
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genital warts by visual inspection, cervical changes ID'd by routine Pap tests
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Prevention of HPV
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limited # of partners, use of condoms, regular Pap smears
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VLP vaccines contain...
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no viral DNA, only proteins expressed by viruses
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Tx of HPV
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-surgery or cryotherapy for warts, but common recurence
-podophyllin, an anti-mitotic |