Micro: HPV Flashcards
What is the basic virology of HPV?
non-enveloped, icosahedral capsid
dsDNA, circular
highly species specific
What is the genome expression of HPV?
non-coding regions: regulatory elements
ORFs (only 8-9): early genes = E1, E2 - transcription, translation, and E6, E7 - oncogenes, late genes = major (L1) and minor (L2) capsid proteins
What are the genotypes and tropism of HPV?
cutaneous: common warts
mucocutaneous: classified by relationship to cervical cancer
What are the phases of HPV inf?
inoculation: viral particles enter areas of microtrauma and infect basal cells
incubation: 6 wks - 8 mos, no apparent lesions, can remain latent or progress
active expression: rapid viral replication, lasts 3-6 mos
host containment phase: at least 3 mos after active expression
What are the main HPV infection types?
subclinical, cancer, warts, latent, productive neoplastic
How is HPV diagnosed?
clinical = indirect: cytology (koilocytosis), colposcopy, histology (parakeratosis, acanthosis)
HPV DNA detection = direct: in situ hybridization, PCR, probes
What are the 3 clinical indications for clinical testing of high risk HPV types?
primary screening for cervical cancer: women age >30 yrs combined w pap reduces to pap/5 yrs
triage low grade pap abnormalities
post treatment surveillance
What are the characteristics of latent inf?
genome episomal, intranuclear, in basal layer
1 copy/cell
no clinical manifestations
may be reactivated later if immune status change
What are the characteristics of productive inf?
benign, little malignant potential HPV DNA episomal minimal oncogene expression clinical warts or subclinical lesions cell death/shedding releases inf particles (not immortalized)
What are the characteristics of neoplastic inf?
circular genome interrupted at E2
integration of viral DNA into host DNA
unrestrained translation of E6 and E7 oncogenes
What do E6 and E7 oncoproteins do and what factors can influence their action?
bind with and accelerate degradation of host p53 and Rb tumor suppressors
influenced by age, immune status, immature cervix, parity, tobacco
What is the relationship b/w HPV and cervical cancer?
HPV is necessary but not sufficient
HPV 16 is most oncogenic
What are the characteristics of anal carcinoma in regards to HPV?
most HPV related (16)
MSM, HIV inf (even w HAART), tobacco use
more common in women but increasing in both
no screening prevention guidelines
What are the characteristics of head and neck cancers in regard to HPV?
increasing in men and women - most in younger non-smokers/non-use of alcohol
risk increased w multiple vaginal and oral partners, genital neoplasia, HIV, anal neoplasia
lots of oropharyngeal - mostly HPV 16
How is HPV transmitted?
mostly sexual: rare, but happens, w no penetration
1/3 to 1/2 partners inf, often w different types
non-sexual = rare vertical transmission: conjunctival, perianal, laryngeal (can be life threatening obstruction/malignant transformation), maybe fomites