HPV 1

Question 1

4 steps in cervical cancer development (IPPI)

Answer 1

infection of metaplastic epithelium at cervical transformation zone, persistence of infection, progression to cervical precancer, invasion thru basement memb below epithel

Question 2

most women worldwide infected w at least ? HPV types

Answer 2

1 or several

Question 3

do most infections persist

Answer 3

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)

Question 4

cervical transformation zone

Answer 4

cervical cancer ~arise from ring of mucosa = CTZ. stratified squamous epithel replaces glandular epithel

Question 5

how are genital HPV infections transmitted

Answer 5

mucosa-to-mucosa contact

Question 6

viral particles reach germinal cells in basal layer how?

Answer 6

via tiny tears to mucosa

Question 7

how many types HPV? what they infect?

Answer 7

over 40, infect epithel lining of anogenital tract

Question 8

how many types HPV assoc w cervical cancer & high risk? probable risk? low risk?

Answer 8

15 (cause cancer), 3, 12

Question 9

2 most carcinogenic HPV types? responsible for 70% cervical cancer & ~50% pre cervical cancer?

Answer 9

HPV16 & 18

Question 10

2 HPV types responsible for ~90% genital warts (NOT pre-cancer)?

Answer 10

HPV6 & 11

Question 11

natural history IRPP

Answer 11

infection, resolution, persistence, progression

Question 12

strongest factor affecting absolute risk of viral persistence, progression

Answer 12

HPV type

Question 13

HPV16 absolute risk of precancer diagnosis

Answer 13

HPV16 40% cases progress after 3-5 yrs of persistent infection

Question 14

lag time bw infection & appearance of 1st microscopic evidence of precancer

Answer 14

~within 5 yrs. (histological precancer within as little as 2 yrs)

Question 15

avg age of precancer diagnosis

Answer 15

25-35

Question 16

human papillomavirus genome encodes only ? genes

Answer 16

8

Question 17

primary HPV oncoproteins? how many cellular targets? most key?

Answer 17

E6, E7. numerous targets, esp. p53 & pRB (retinoblastoma tumor suppressor protein)

Question 18

E6 inhibition of p53

Answer 18

block apoptosis

Question 19

E7 inhib of pRB

Answer 19

abrogate/escape cell cycle arrest

Question 20

E7 is?

Answer 20

primary transforming protein

Question 21

E6 & E7 expressed at ? levels during infection

Answer 21

low levels

Question 22

at undefined pt in progression, E6 & E7 expression deregulated by ? what happens?

Answer 22

genetic/epigenetic changes. lead to overexpression in full thickness epithel lesion

Question 23

diagnostic classification NLHC

Answer 23

normal, LSIL, HSIL, carcinoma (after dysplasia)

Question 24

LSIL

Answer 24

low grade squamous intraepithelial lesion. viral infection but not pre-cancer … change shape of halo (clear space around nuclei)

Question 25

HSIL

Answer 25

high grade. pre-cancer (progression) ... lose halos, little cytoplasm throughout

Question 26

normal squamous mucosa

Answer 26

lots nucleus, little cytoplasm, but more cytoplasm, spread on top

Question 27

invasive cancer assoc w

Answer 27

integration of HPV genome into host genome = key biomarker distinguish infection from precancer

Question 28

why might integration not be necessary to cause invasion?

Answer 28

not all women w invasive cancers have measurable integration

Question 29

risk of cervical cancer ~fxn of

Answer 29

HPV infection & lack effective screening (external factors minor compared to high primary risks of most carcinogenic HPV types)

Question 30

what can double risk of pre-cancer, cancer among women infected w carcinogenic HPV

Answer 30

smoking, multi-parity, LT use of OCPs

Question 31

cervical cancer prevention

Answer 31

1. screening. pap smear 2. triage of equivocal results 3. colposcopy guided biopsy of abnormal results 4. decide to treat or not 5. treat / post-treat follow up. 6. return to normal screening

Question 32

screening - cytology

Answer 32

[bethesda system], normal, [ASCUS, LSIL, HSIL], carcinoma

Question 33

ASCUS

Answer 33

atypical squamous cells of undetermined significance... equivocal changes (some but criteria to diagnose HPV not met)

Question 34

glass slide

Answer 34

smear stain vs wet mount

Question 35

LSIL

Answer 35

binucleate or large nucleus, with halo

Question 36

carcinoma

Answer 36

huge nucleus, red nucleoli

Question 37

traditional triage

Answer 37

normal - repeat every 3 yrs ascus & lsil - repaet pap in 6 months, refer to colposcopy if still abnormal hsil/carcinoma - straight to colposcopy

Question 38

colposcopy

Answer 38

close up look at cervix.

Question 39

CIN

Answer 39

cervical intra-epithelial neoplasia

Question 40

colposcopic biopsy. depend on diagnosis & age of patient, treatment could be ?

Answer 40

cryotherapy, LEEP, cold knife cone biopsy

Question 41

loop electrosurgical excision procedure

Answer 41

wire w current running thru, slice out tissue, reduce bleeding

Question 42

post treatment follow up

Answer 42

colposcopy, pap smear. return to routine screening

Question 43

direct HPV testing

Answer 43

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)