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
What are risk factors common to HPV inf and cervical cancer?
number of sex partners
male partner sexual behavior
immune compromise
lower socioeconomic status
What can cause morbidity due to HPV inf in men?
genital warts, anal cancer, head and neck cancers
What is the natural history of HPV?
usually transient - clears in avg of 8 mos, esp if young and low risk type
most persistent inf is actually re-inf
persistent, high risk type, older more risk for cancer
What is the general treatment for HPV?
only if symptomatic warts, no treatment for subclinical, spontaneous regression 60-70%
treating male has no effect on female
What are the treatments for genital warts?
topical - antimitotics, immunomodulators, tea extracts
mechanical removal
What is the treatment for HPV related neoplasia?
observe low grade, treat high grade (ablation or excision)
invasive cervix cancer: radical surgery, XRT
How does HPV evade immune detection?
natural humoral response is weak
intraepithelial inf
capsid expressed late or not at all
oncogene products blunt local immune response
How is the HPV life cycle tied to squamous epithelium maturation?
early genes expressed in less mature cells
late genes expressed in more mature cells
What are the different fxns of the HPV vaccine?
prophylactic: mimic L1 capsid protein and stimulate humoral response
treatment: E6/7 products, efficacy not proven
What are the two types of prophylactic HPV vaccines?
quadrivalent - 6, 11, 16, 18 - men and women
bivalent - 16, 18 - women only
What are the features of the prophylactic HPV vaccines?
highly efficacious and safe
virus-like particles: empty protein capsids, self assemble, no HPV genetic material
