7.2 Viruses and cancer

Question 1

Briefly describe the 4 stages of the Eukaryotic cell cycle and what occurs in each

Answer 1

G1: cellular content (excluding chromosomes) are duplicated
S: genetic material is amplified
G2: proof reading and repair mechanisms
M: mitosis occurs

Between M and G1 phase: the cell may enter GO, where the cells reside at a not dividing state

Question 2

What is an oncogene?

Answer 2

An oncogene is a sequence of deoxyribonucleic acid (DNA) that has been altered or mutated from its original form, the proto- oncogene

Genetic material carries the ability to induce cancer

Question 3

What is the fastest growing STI among young adults

Answer 3

HPV

Question 4

How is HPV classified

Answer 4

Classified as high risk or low risk

Question 5

What is the most likely mode of transmission of HPV

Answer 5

Through direct contact with infected skin

Question 6

How do we test males vs females for HPV

Answer 6

Males –Only visual exam

Females –Visual exam and detection through smears

Question 7

Describe the structure of HPV

Answer 7

• double stranded DNA virus
• enveloped
• has a capsid
• base pairs (bp) arranged in a circle and contain 2 vital proteins

Question 8

What are the 2 classes of proteins contained in the HPV virus and what is each responsible for?

Answer 8

L1 and L2 (late proteins) responsible for viral structure

E1-E6 (early proteins) responsible for virus replication

Question 9

What is the main characteristic of HPV infection?

What happens if these aren’t treated?

Answer 9

Warts that range in size and can have a “cauliflower” like appearance called a condyloma which appears on the skin surface, usually small but if left untreated can grow dangerously large and can undergo necrosis

Question 10

List 4 things that may occur if HPV goes untreated

Answer 10

1) Transmission to sex partners and newborns
2) Warts may grow and spread if left untreated
3) May cause cervical cancer
4) Block openings from anus, vagina and urethra

Question 11

What is a koilocyte when is it seen?

Answer 11

A koilocyte is a squamous epithelial cell that has undergone a number of structural changes due to HPV infection.

Seen on a HPV smear test (females)

Question 12

What does CIN stand for?

Answer 12

cervical intraepithelial neoplasia

Question 13

What is meant by Grade?

What does “low grade” vs “high grade” tell us?

Answer 13

Grade: The degree of differentiation of the neoplasm

Low grade: implies slow growth, resembles parent tissue
High grade: implies fast growth, tissue is poorly differentiated

Question 14

How do we divide CIN into grades?

Answer 14

1, 2 and 3 (It is often difficult to distinguish between grades)

CIN 1: low risk.
CIN 2 and 3: high risk

Question 15

What changes might we see in the squamous epithelium in a cervical biopsy? How do we classify these

Answer 15

Koilocytosis, indicating viral infection

Use CIN, grade 1, 2 or 3.

Question 16

List 3 things associated with an increased incidence of CIN

Answer 16

1) Infection with Trichomonas Vaginalis
2) Early age of first sexual intercourse
3) Number of different sexual partners

Question 17

What’s the term used to indicate how far a tumour has spread?

Answer 17

Staging
S1- confined to the cervix
S4- extensive spread beyond the genital tract

Question 18

Describe the prognosis of a microinvasion vs a deeper invasion of HPV

Answer 18

The prognosis of microinvasion is good and treatment can be relatively conservative

If the invasion is more deep, the prognosis is serious, because the likelihood of further spread increases dramatically

Question 19

Which HPV types are low risk and associated with benign warts?

Which HPV types are high risk and associated with CIN 2 and 3 and invasive carcinomas

Answer 19

HPV types 6 and 11: associated with benign warts: low risk

HPV types 16 and 18: mainly found in CIN 2 and 3 and in invasive carcinoma: high risk

Question 20

Which HPV type is the most common In squamous cell carcinoma

Which HPV type is most commonly associated with adenocarcinoma

Answer 20

HPV type 16 is commonest in squamous cell carcinoma.

HPV type 18 is more associated with adenocarcinoma

Question 21

Why are types 16 and 18 most high risk?

Answer 21

They encode the E6 and E7 proteins that bind p53 and pRB ➞ locks the suppression activity allowing neoplasms to occur

Question 22

What is p53 and pRB

Answer 22

Both tumour suppressor genes, promotes apoptosis of genetically damaged cells

p53 = guardian of the genome
pRB = restriction point in cell cycle

Question 23

List the 3 main ways integration of the HPV virus occurs and how these may lead to neoplasms

Answer 23

1) Linear virus integrating into a tumour suppressor gene (eg. integration with p53) ➞ produces a non-functional protein which no longer suppresses the activity of TSG’s
2) Enhanced expression of oncogenes ➞ virus DNA may integrate upstream of the oncogene and into nearby regions causing enhanced oncogene expression
3) Viral DNA integrates into areas causes chromosomal rearrangement ➞ leads to altered expression of genes involved and cellular instability

Question 24

Explain how Initial infection of HPV occurs

Answer 24

Infection of mucosal epithelium through micro-injury allows virus to enter and infect the basal cell layer of stratified squamous epithelial cells through E6 and E7 proteins

This promotes continuous cell proliferation ➞ infected cells can move up through the skin layers and shed new virions in the squamous epithelia which can infect other cells

Note: the body immune system in some cases will be able to detect and resolve this infection

Question 25

Explain how a chronic HPV infection can occur

Answer 25

If immune system of the host does not resolve the viral infection and it persists for a long period of time, the viral DNA can integrate into the host genome leading to uncontrolled viral oncogene production and host cell transformation If low risk type ➞ warts will form If high risk type ➞ cells may undergo a malignant change which can lead to a HPV induced malignancy

Question 26

Explain the effect of E6 and E7 proteins on the host

Answer 26

E6 binds to the p53 ➞ results in degradation of the p53 protein E7 binds to the retinoblastoma protein ➞ promotes progression through the cell cycle.

Question 27

Once we do a cervical smear, what 2 things must we identify and how? If sample is positive for both, what is the following step?

Answer 27

1) Is there a malignant change 2) Is there the presence of the HPV virus (use hybridisation) (+) for both: visual examination of the cervix ➞ diluted acetic acid is put onto the cervix which will cause a slight change in the appearance of cells that are damaged (white colour) which will indicated the degree of change in the cervix

Question 28

How do we prevent cervical carcinoma?

Answer 28

vaccinate young women against HPV infection

Question 29

What are the 2 types of Herpes virus and how do they differ? | What is the characteristic of Herpes and what can these lead to?

Answer 29

HSV-1: Oral Herpes HSV-2: Genital Herpes Herpes is characterised by small blisters occuring around the mouth or the genitals and rectum can in some cases lead to painful ulcerative lesions

Question 30

List 3 ways in which Herpes can be transmitted

Answer 30

1) Sexual Contact 2) Contact with herpes sore 3) Mother to child can be transmitted anywhere there is a break in the skin and mucous membrane.

Question 31

Is genital herpes associated with cervical cancer?

Answer 31

NO!!!

Question 32

Explain the mechanism of a Herpes infection

Answer 32

1) Herpes attaches and fuses to the cell membrane 2) initial attachment triggers a cascade of molecular interactions involving viral and host cell proteins 3) Leads to penetration of the viral nucleocapsid which is then transported to the nuclear membrane 4) viral DNA is released and new viruses are synthesised and assembled 5) virions use the nuclear membrane to create an envelop and exit the cell As HSV kills the epithelia, blisters filled with clear straw coloured fluid form ➞ blisters eventually burst, releasing a large number of virus particles and can turn into an ulcer

Question 33

Why does genital Herpes significantly increase your risk of HIV?

Answer 33

open Herpes lesions provide an easy route of entry into the body (hence very prone to secondary infections, especially HIV)

Question 34

How do we treat Herpes

Answer 34

No cure but can use antivirals ➞ Acyclovir competitively inhibits and inactivates HSV-specific DNA polymerases preventing further viral DNA syntheses without effecting the normal cellular processes. This can reduce number of herpes lesions and reduce risk of spreading between sexual partners or childbirth

Question 35

What cancer is highly associated with the Epstein-Barr virus? How can this occur?

Answer 35

Burkitt’s Lymphomas EBV infects B lymphocytes and promotes cell survival and proliferation This increases the chance of genetic mutation occurring during replication ➞ i.e. the virus is not directly mutagenic but acts as a polyclonal B cell mitogen which sets the stage for acquisition of mutations that produce cancer.