4.25 - HPV and cervical cancer

Question 1

Discuss the relative incidence of and mortality from cervical cancer in developed versus
developing countries.

Answer 1

cervical cancer is not a top 10 in the US
worldwide: incidence rate - 13.3/100,000 women (#4), mortality rate - 7.3/100,000 women (#3)

Question 2

Describe the ethnic/racial groups at highest risk for cervical cancer. Distinguish between
the risk of incidence and mortality

Answer 2

hispanic = highest rate
black = highest death

Question 3

Propose an explanation for the discrepancy between the incidence rate and mortality
rate for cervical cancer in various ethnic groups. Why might Black women in the US have
a lower incidence rate of cervical cancer than Hispanic women, but a higher death rate?

Answer 3

?

Question 4

Why is it significant that the CDC data show that cervical cancer is not a top 10 newly
diagnosed cancer or cause of death in the US?

Answer 4

?

Question 5

Describe the structure of HPV in terms of its genetic and protein components. Include
mention of capsids, L1, L2, and VLP

Answer 5

-double stranded circular DNA episome
-surrounded by 72 pentameric (5-sided) capsids
–>each capsid is a viral protein
L1 and L2 genes encode for capsid proteins
-individual capsids will assemble into virus-like particles (VLPs) when expressed in microbial organisms
-VLPs lack viral DNA

Question 6

Define oncogene

Answer 6

gene that causes transformation of normal cells into cancerous tumor cells; especially viral gene that transforms host cell into tumor cell

Question 7

Explain how some types of HPV are non-ocogenic while other are oncogenic. Include a
classification of HPVs 6, 11, 16 and 18 and the diseases that are associated with them.

Answer 7

oncogenic - affect anal and genital areas, about 40 types: high risk (16+18) and low risk types (6+11)
non-oncogenic - common body warts around hand and feet
HPV 16: 50-60% cervical cancer
HPV 18: 10-20% of all cerv cancers
HPV 6 and 11 (low risk): 90% genital warts
-each type of HPV has a unique capsid protein

Question 8

Describe the anatomy of the cervix, including the location of the squamous cell

Answer 8

-cervix separates uterus from vagina
-cervix has flat squamous cells (plate-like, thin and flat) in region near vagina

Question 9

Define squamous, dysplasia, carcinoma, and malignant neoplasm

Answer 9

squamous - plate-like ; thin and flat
dysplasia - alteration in size, shape, and organization of adult cells
carcinoma - abnormal cells have not spread beyond where they first formed
CIN - cervical intraepithelial neoplasia (dysplasia)
malignant neoplasm - abnormal cells tending to infiltrate surrounding tissues

Question 10

Describe the progression of mild/moderate dysplasia LSIL) to moderate/severe dysplasia
(HSIL; carcinoma in situ) to invasive cancer at the cellular level.

Answer 10

HPV infection doesn’t always lead to cervical cancer
-80% of infections are transient, asymptomatic, and resolve without treatment and HPV is no longer detectable in cervix
-in women with intact immune systems, HPV infection generally resolves without intervention within 18 to 24 months
LSIL - low grade squamous intraepithelial lesion (also called mild dysplasia)
HSIL - high grade squamous intraepithelial lesion (moderate to severe dysplasia)
-average time from infection to invasive cervical cancer is 15 years

Question 11

Explain why not all HPV infection leads to invasive cervical cancer. Include mention of
the typical time course for infection to invasive cancer

Answer 11

Question 12

Explain the progression of HPV infection to invasive cervical cancer at the molecular
level. Include mention of cervical epithelium, basal cells, basement membrane,
midzone, superficial zone, microabrasions, early HPV genes, late HPV genes, progeny
virions, shed virus, and genome integration

Answer 12

1. Basal cells in cervical epithelium rest on basement membrane (basal cells divide and migrate toward superficial zone)
2. Sexually transmitted HPV is thought to access basal cells through micro-abrasians in cervical eptihelium
3. Following infection, early HPV genes (E1, E2, E4, E5, E6, and E7) are expressed and viral DNA replicates from episomal DNA
4. In upper layers of epithelium (midzone and superficial zone) viral genome is replicated further, and late genes (L1 and L2) are expressed
5. L1 and L2 encapsidate viral genomes to form progeny virions in nucleus
6. Shed virus can then initiate a new infection
7. Low-grade intraepithelial lesions support productive viral replication
8. Unknown number of high risk HPV infections progress to high-grade cervical intraepithelial neoplasia (HSIL)
9. Progression of untreated lesions to invasive cancer is associated with integration of HPV genome into host chromosomes (red nuclei), with subsequent up-regulation of E6 and E7 oncogene expression

Question 13

Answer 13

up regulation of E6 and E7 oncogenes

Question 14

Discuss the age at which most women are exposed to transient HPV infection

Answer 14

among women during their teens and 20s after initiation of sexual activity

Question 15

Discuss the age at which peak prevalence of cervical precancerous conditions is
observed

Answer 15

approximately 10 yrs later

Question 16

Discuss the age at which peak prevalence of invasive cervical cancers is observed

Answer 16

40 to 50 years of age

Question 17

Explain the timing of screening for cervical cancer and the types of screenings that are
performed

Answer 17

repeated rounds of cytologic examination including pap smears, HPV vaccination of adolescents, one or 2 rounds of HPV screening during peak ages of treatable precancerous conditions

Question 18

Explain what the Pap smear and HPV DNA test are and what can be identified in each of
these screening tests

Answer 18

screening test to detect premalignant and malignant (cancerous) cells in cervix
-cervical cells are collected from squamous cells near transition zone, checked under microscope for abnormalities
-molecular testing can detect presence of high risk-types of HPV on same sample (normal, precancerous lesion, or invasive carcinoma)

Question 19

Explain how abnormal Pap or HPV DNA tests are treated. Include mention of LEEP and
cryotherapy and why some cases do not require treatment

Answer 19

LSIL doesnt require treatment in younger women bc it usually goes away by itself
if LSIL progresses to HSIL, then it is treated
-Loop electrosurgical excision procedure (LEEP) - thin wire loop that carries electric current is used to remove abnormal areas of cervix
-cryotherapy

Question 20

Explain how the HPV vaccine works. Include mention of VLPs and the specific VLPs
included in Gardasil

Answer 20

-HPV capsid proteins can assemble into virus-like particles (VLPs)
–> *VLPs lack viral DNA and cannot cause infection
-specific HPV VLPs elicit robust antibody response specific to HPV type (HPV 16)
*Gardasil now includes VLPS from HPV 16, 18, 31, 33, 45, 52, 58, 6, and 11

Question 21

Explain who should get the HPV vaccine and why. Include mention of specific age
groups, gender, and other health-related factors.

Answer 21

approved for females 9-26 yrs
-prior/after onset of sex, vax can protect against HPV types not already acquired
-rcmded for immunosuppressed women
-not for newborns
approved for males 9-26yrs
-for prevention against genital warts (6 and 11)
-males are less likely to be dxd with HPV related cancers, but are invloved in transmission