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31 Cards in this Set

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