HPV 1 Flashcards
4 steps in cervical cancer development (IPPI)
infection of metaplastic epithelium at cervical transformation zone, persistence of infection, progression to cervical precancer, invasion thru basement memb below epithel
most women worldwide infected w at least ? HPV types
1 or several
do most infections persist
most clear in 1-2 yrs & 10% persist, a fraction progress to precancer (depend on HPV type), another invade (20-30% large precancers invade 5 or 10 yrs later)
cervical transformation zone
cervical cancer ~arise from ring of mucosa = CTZ. stratified squamous epithel replaces glandular epithel
how are genital HPV infections transmitted
mucosa-to-mucosa contact
viral particles reach germinal cells in basal layer how?
via tiny tears to mucosa
how many types HPV? what they infect?
over 40, infect epithel lining of anogenital tract
how many types HPV assoc w cervical cancer & high risk? probable risk? low risk?
15 (cause cancer), 3, 12
2 most carcinogenic HPV types? responsible for 70% cervical cancer & ~50% pre cervical cancer?
HPV16 & 18
2 HPV types responsible for ~90% genital warts (NOT pre-cancer)?
HPV6 & 11
natural history IRPP
infection, resolution, persistence, progression
strongest factor affecting absolute risk of viral persistence, progression
HPV type
HPV16 absolute risk of precancer diagnosis
HPV16 40% cases progress after 3-5 yrs of persistent infection
lag time bw infection & appearance of 1st microscopic evidence of precancer
~within 5 yrs. (histological precancer within as little as 2 yrs)
avg age of precancer diagnosis
25-35
human papillomavirus genome encodes only ? genes
8
primary HPV oncoproteins? how many cellular targets? most key?
E6, E7. numerous targets, esp. p53 & pRB (retinoblastoma tumor suppressor protein)
E6 inhibition of p53
block apoptosis
E7 inhib of pRB
abrogate/escape cell cycle arrest
E7 is?
primary transforming protein
E6 & E7 expressed at ? levels during infection
low levels
at undefined pt in progression, E6 & E7 expression deregulated by ? what happens?
genetic/epigenetic changes. lead to overexpression in full thickness epithel lesion
diagnostic classification NLHC
normal, LSIL, HSIL, carcinoma (after dysplasia)
LSIL
low grade squamous intraepithelial lesion. viral infection but not pre-cancer … change shape of halo (clear space around nuclei)
HSIL
high grade. pre-cancer (progression) … lose halos, little cytoplasm throughout
normal squamous mucosa
lots nucleus, little cytoplasm, but more cytoplasm, spread on top
invasive cancer assoc w
integration of HPV genome into host genome = key biomarker distinguish infection from precancer
why might integration not be necessary to cause invasion?
not all women w invasive cancers have measurable integration
risk of cervical cancer ~fxn of
HPV infection & lack effective screening (external factors minor compared to high primary risks of most carcinogenic HPV types)
what can double risk of pre-cancer, cancer among women infected w carcinogenic HPV
smoking, multi-parity, LT use of OCPs
cervical cancer prevention
- screening. pap smear
- triage of equivocal results
- colposcopy guided biopsy of abnormal results
- decide to treat or not
- treat / post-treat follow up.
- return to normal screening
screening - cytology
[bethesda system], normal, [ASCUS, LSIL, HSIL], carcinoma
ASCUS
atypical squamous cells of undetermined significance… equivocal changes (some but criteria to diagnose HPV not met)
glass slide
smear stain vs wet mount
LSIL
binucleate or large nucleus, with halo
carcinoma
huge nucleus, red nucleoli
traditional triage
normal - repeat every 3 yrs
ascus & lsil - repaet pap in 6 months, refer to colposcopy if still abnormal
hsil/carcinoma - straight to colposcopy
colposcopy
close up look at cervix.
CIN
cervical intra-epithelial neoplasia
colposcopic biopsy. depend on diagnosis & age of patient, treatment could be ?
cryotherapy, LEEP, cold knife cone biopsy
loop electrosurgical excision procedure
wire w current running thru, slice out tissue, reduce bleeding
post treatment follow up
colposcopy, pap smear. return to routine screening
direct HPV testing
screen in ontario, pay $100 to get HPV test along w screening (test neg to reassure/confirm cure post-treatment, indicate who should go to colposcopy & can use post-colposcopy if no pre-cancer found)
