Micro: HPV Flashcards

1
Q

What is the basic virology of HPV?

A

non-enveloped, icosahedral capsid
dsDNA, circular
highly species specific

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2
Q

What is the genome expression of HPV?

A

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

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3
Q

What are the genotypes and tropism of HPV?

A

cutaneous: common warts
mucocutaneous: classified by relationship to cervical cancer

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4
Q

What are the phases of HPV inf?

A

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

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5
Q

What are the main HPV infection types?

A

subclinical, cancer, warts, latent, productive neoplastic

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6
Q

How is HPV diagnosed?

A

clinical = indirect: cytology (koilocytosis), colposcopy, histology (parakeratosis, acanthosis)
HPV DNA detection = direct: in situ hybridization, PCR, probes

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7
Q

What are the 3 clinical indications for clinical testing of high risk HPV types?

A

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

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8
Q

What are the characteristics of latent inf?

A

genome episomal, intranuclear, in basal layer
1 copy/cell
no clinical manifestations
may be reactivated later if immune status change

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9
Q

What are the characteristics of productive inf?

A
benign, little malignant potential
HPV DNA episomal
minimal oncogene expression
clinical warts or subclinical lesions
cell death/shedding releases inf particles (not immortalized)
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10
Q

What are the characteristics of neoplastic inf?

A

circular genome interrupted at E2
integration of viral DNA into host DNA
unrestrained translation of E6 and E7 oncogenes

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11
Q

What do E6 and E7 oncoproteins do and what factors can influence their action?

A

bind with and accelerate degradation of host p53 and Rb tumor suppressors
influenced by age, immune status, immature cervix, parity, tobacco

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12
Q

What is the relationship b/w HPV and cervical cancer?

A

HPV is necessary but not sufficient

HPV 16 is most oncogenic

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13
Q

What are the characteristics of anal carcinoma in regards to HPV?

A

most HPV related (16)
MSM, HIV inf (even w HAART), tobacco use
more common in women but increasing in both
no screening prevention guidelines

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14
Q

What are the characteristics of head and neck cancers in regard to HPV?

A

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

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15
Q

How is HPV transmitted?

A

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

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16
Q

What are risk factors common to HPV inf and cervical cancer?

A

number of sex partners
male partner sexual behavior
immune compromise
lower socioeconomic status

17
Q

What can cause morbidity due to HPV inf in men?

A

genital warts, anal cancer, head and neck cancers

18
Q

What is the natural history of HPV?

A

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

19
Q

What is the general treatment for HPV?

A

only if symptomatic warts, no treatment for subclinical, spontaneous regression 60-70%
treating male has no effect on female

20
Q

What are the treatments for genital warts?

A

topical - antimitotics, immunomodulators, tea extracts

mechanical removal

21
Q

What is the treatment for HPV related neoplasia?

A

observe low grade, treat high grade (ablation or excision)

invasive cervix cancer: radical surgery, XRT

22
Q

How does HPV evade immune detection?

A

natural humoral response is weak
intraepithelial inf
capsid expressed late or not at all
oncogene products blunt local immune response

23
Q

How is the HPV life cycle tied to squamous epithelium maturation?

A

early genes expressed in less mature cells

late genes expressed in more mature cells

24
Q

What are the different fxns of the HPV vaccine?

A

prophylactic: mimic L1 capsid protein and stimulate humoral response
treatment: E6/7 products, efficacy not proven

25
Q

What are the two types of prophylactic HPV vaccines?

A

quadrivalent - 6, 11, 16, 18 - men and women

bivalent - 16, 18 - women only

26
Q

What are the features of the prophylactic HPV vaccines?

A

highly efficacious and safe

virus-like particles: empty protein capsids, self assemble, no HPV genetic material