8.2 Viral infections & cancers Flashcards
cell cycle machinery controls what ?
cell proliferation
Cancer is a disease of ?
inappropriate cell proliferation
What’s oncogene ?
genetic material that carries the ability to induce cancer
A checkpoint is a ….. mechanism in the cell cycle
regulatory
What is p53 ?
human suppressor gene
What are 2 checkpoints in cell cycle ?
- G1/S checkpoint
- G2/M checkpoint
p53 exerts its effects mainly through what protein ?
p21
what does p21 inhibit ? which does what ?
cyclin-dependent kinases (CDKs), prevent the progressing to next phase
what does p53 arrest ?
cell cycle for DNA repair if damage is detected
When p53 arrests cell cycle for DNA repair if damage is detected what does it ensure ? [change ?!]
DNA repair before cell division induces DNA repair genes
If the DNA damage is irreparable , what does p53 do ?
promotes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX and activation of caspases
What are oncogenic viruses ?
viruses that can cause cancer by altering the genetic material of host cells
Cancers caused by human papillomavirus (HPV) ?
- cervical
- anal
- oropharyngeal
- vulvar
- vaginal
- penile
Types of HPV ?
- high-risk HPV types include HPV-16 and HPV-18
cancers caused by epstein-barr virus ?
- Burkitt lymphoma
- Hodgkin lymphoma
- nasopharyngeal carcinoma
- gastric cancer
What is the primary mechanism by which epstein-barr virus (EBV) contributes to cancer development?
** latent infection of B cells and epithelial cells.**
[extra] During latency, the virus expresses specific genes that drive cell proliferation, prevent apoptosis, and evade immune detection.
cancers caused by heptitis B virus (HBV) ?
- hepatocellular carcinoma (liver cancer)
Mechanism of how hepatitis B virus leads to cancer ?
HBV can cause chronic liver infection, which may lead to liver cirrhosis, inflammation, and eventually hepatocellular carcinoma
cancers caused by hepatitis C virus (HCV )?
- hepatocellular carcinoma (liver cancer)
Mechanism of how hepatitis C virus leads to cancer ?
HCV can cause chronic liver infection, which may lead to liver cirrhosis, fibrosis, and eventually hepatocellular carcinoma
Cancers caused by human T-cell lymphotropic virus type 1 (HTLV-1) ?
adult T-cell leukemia/ lymphoma (ATLL)
mechanism of HTLV-1 (human T-cell lymphotropic virus type 1) to result in cancer ?
integration of viral DNA into host T-cell genome
cancers caused by Kaposi’s Sarcoma-associated Herpesvirus or Human Herpesvirus 8 (KSHV/HHV-8)
- Kaposi’s sarcoma
- primary effusion lymphoma
- multicentric Castleman disease.
mechanism of Kaposi’s Sarcoma-associated Herpesvirus or Human Herpesvirus 8 (KSHV/HHV-8) leading to causing cancer ?
latent infection in endothelial cells
cancers caused by merkel cell polyomavirus (MCV) ?
merkel cell carcinoma
mechanism for merkel cell polyomavirus (MCV) to cause cancer ?
integration of viral DNA leading to mutations
HPV is the most common….
sexually transmitted infection (STI)
Percentage of sexually active unvaccinated men and women that get the HPV virus at some point in their life ?
80%
Transmission of HPV ?
- more likely transmitted through direct contact
- with infected skin (i.e. wart is present)
testing for HPV ? males & females
- males - only visual exam
- females - visual exam & detection through smears
early proteins with HPV
E1- E7
what are HPV 6 and HPV 11 the cause of ? [remove]
- benign lesions of skin (warts)
- mucous membrane of the genital and anal areas
- extragenital (papillomas of the mouth )
- respiratory (recurrent respiratory papillomatosis)
What are HPV 16 and HPV 18 involved in the development of ?
- precancerous lesions
- cancers of various organs first and foremost the cervix
What are condylomata acuminata ?
benign anogenital warts most often caused by HPV types 6 and 11
What other types of warts other than condylomata acuminata can HPV types 6 and 11 cause?
laryngeal and oropharyngeal warts
How long is the incubation period for warts caused by HPV?
1 to 6 months
What are the characteristics of visible anogenital warts?
soft, moist, minute pink or gray polyps that can enlarge, become pedunculated, have rough surfaces, and may occur in clusters
What symptoms might patients with anogenital warts experience?
Although usually asymptomatic, some patients may experience itching, burning, or discomfort
Where do anogenital warts commonly occur in men?
commonly under the foreskin, on the coronal sulcus, within the urethral meatus, and on the penile shaft.
They may occur around the anus and in the rectum, especially in homosexual men
Where do anogenital warts commonly occur in women?
the vulva, vaginal wall, cervix, and perineum.
The urethra and anal region may also be affected.
Which HPV types usually cause flat endocervical or anal warts, and why are they difficult to diagnose?
HPV types 16 and 18
If condylomata acuminata (anogenital warts caused by HPV) gone untreated what happens ?
- Transmission to sex partners and newborns
- Warts may grow and spread if left untreated
- May cause cervical cancer
- Block openings from anus, vagina and urethra
Cervical cancer develops from ..?
pre-cancerous stage of cervix known as cervical intraepithelial neoplasia (CIN)
change by persistence infection (dysplasia)
Cervical cancer appears to be cause by infection with what HPV types ? what’s the different between the types ?
- 16 , 18 = most common high risk , associated with pre-malignant regions
- 31, 33, 35, 39 =high risk
HPV type 16 most common which carcinoma ?
squamous cell
HPV type 18 more associated with what carcinoma ?
adenocarcinoma
Type of HPV makes a difference in terms of the likelhood of …. ?
malignancy
Type of HPV makes a difference in terms of the likelihood of malignancy:
- subtypes 2, 4 :
- HPV types 6 & 11 :
- HPV types 16 & 18:
- common , skin warts
- associated with benign genital warts, low risk
- mainly found in CIN 2 and 3 and in invasive carcinoma, high risk
List 4 risk factors for cervical cancer
- younger age at first intercourse
- a high lifetime number of sex partners
- cigarette smoking - weakens immune system
- immunodeficiency - weaken immune system
- oral contraceptives
- sexually transmitted disease
Why is a younger age at first intercourse a risk factor for cervical cancer ?
the cells in the transformation zone are actively dividing and replicating, making them more vulnerable to HPV-induced changes.
Regardless of sexual history, what shoudl clinicians assume with women and HPV infection ?
women have been exposed to someone with HPV because it’s present (ubiquitous)
symptoms of cervical cancer?
- often asymptomatic
- irregular vaginal bleeding
Larger cervical cancers (tumours grown significant size) symptoms more likely ?
- to bleed spontaneously
- may cause foul-smelling vaginal discharge
- pelvic pain
What are some indicators of advanced (widespread) cervical cancer?
- obstructive uropathy, resulting in urinary issues
- back pain
- leg swelling due to venous or lymphatic obstruction
How might cervical cancer be detected during a pelvic examination?
detect an exophytic necrotic tumor in the cervix
What is CIN ?
cervical intraepithelial neoplasia
how is CIN graded ?
based on histology
CIN grades for cervical cancer ?
- CIN Grade 1: Mild cervical dysplasia (1/3)
- CIN Grade 2: Moderate dysplasia (2/3)
- CIN Grade 3: Severe dysplasia or carcinoma in situ (CIS) (more than 2/3)
- full thickness involvement or carcinoma in situ
Differences in risk between the 3 CIN grades ?
CIN 1: low risk.
CIN 2 & 3: high risk.
CIN 3 is unlikely to regress ..1…; if untreated, it may, over months or years, …2… the basement membrane, becoming …3…
- spontaneously
- penetrate
- invasive carcinoma
What happens when HPV infects cells in the cervix?
HPV viral DNA integrates into host cell’s DNA
How can integration of viral DNA contribute to carcinogenesis (the development of cancer)?
can lead to alterations in genes, disrupting normal cellular functions and potentially triggering carcinogenesis
What are some effects of these alterations in genes caused by HPV integration?
loss of function of certain genes and the enhanced expression of oncogenes, which are genes that promote cell growth and division
How might genetic rearrangement contribute to cancer development in the context of HPV infection?
can lead to further disruptions in cellular processes, potentially promoting the development of cancerous cells
What is meant by viral DNA, when episomal ?
state of viral DNA when exists as a separate entity within host cell’s nucleus rather than being integrated into the host cell’s genome
How does Human Papillomavirus (HPV) contribute to cervical cancer development, and what are the steps involved?
- HPV infects cervical epithelial cells via micro-abrasions, entering through clathrin-coated pits.
- When the viral DNA is episomal, the E2 gene regulates expression of oncogenes E6 and E7.
- Integration into the host genome disrupts E2 gene function.
- Disruption of E2 leads to uncontrolled E6 and E7 expression.
- E6 degrades tumor suppressor gene p53; & E7 inactivates tumor suppressor gene Rb.
- These interactions drive cell cycle progression, potentially leading to cervical cancer development.
How does HPV initially infect epithelial cells in the cervix?
through micro-abrasions, entering the cells via clathrin-coated pits by endocytosis
When the viral DNA is episomal, what role does the E2 gene play in the regulation of viral oncogenes E6 and E7?
crucial role in regulating the expression of the viral oncogenes E6 and E7.
What happens to the viral DNA after integration into the host genome, and how does this affect the E2 gene?
viral DNA integrates into the host genome, disrupting the viral E2 gene
How does the disruption of the E2 gene contribute to cervical cancer development?
leads to uncontrolled expression of viral oncogenes E6 and E7, which are associated with cervical cancer development
What are the specific actions of the viral oncogenes E6 and E7 in promoting cervical cancer?
E6 binds to tumor suppressor gene p53, promoting its degradation, while E7 binds to tumor suppressor gene Rb, causing its inactivation.
What cellular outcome is induced by the interactions of E6 and E7 with tumor suppressor genes?
lead to the transition of the cell to the S phase
[extra] promoting cell proliferation and potentially contributing to the development of cancer.
What is the role of the E6 gene product in HPV infection?
gene product binds to the human p53 tumor suppressor protein, impeding its ability to regulate cell growth.
How does the E7 gene product affect apoptosis in HPV-infected cells?
exerts an anti-apoptotic effect through mutations in the p53 protein, preventing programmed cell death.
What is the consequence of the actions of E6 and E7 on cell growth?
actions of E6 and E7 lead to unregulated and unimpeded cell growth, which can result in cancer transformation.
when does squamous cell carcinoma become invasive ?
when it penetrates the basement membrane
What is cervical screening not for cancer ?
a test
What is cervical screening ? if left untreated it could lead to …?
- method of preventing cancer by detecting and treating early abnormalities
- age 25 - 64
- if left untreated, could lead to cancer in a woman’s cervix
Steps of cervical screening ?
- sample of cells taken from cervix for analysis
- speculum is inserted to open woman’s vagina & spatula used to sweep around the cervix
Most women consider cervical screening procedure to be ?
mildly uncomfortable
Early detection and treatment of cervical cancer can prevent ….1…. % of cancers developing but like other screening tests it may …2.. detect ..3…. that could lead to cancer
- 75%
- not always
- early cell changes
What is the primary method of screening for cervical cancer used in England, Scotland, and Wales?
HPV primary screening
What does the lab do with your sample in HPV primary screening?
The lab tests your sample for high-risk HPV most common (16 and 18)
What determines the next steps after an HPV primary screening?
the test results and tailored to your individual risk
Why is it important to determine the grade of a neoplasm?
it measures the degree of differentiation and helps predict the tumor’s growth rate and aggressiveness
What does a low-grade neoplasm indicate?
well-differentiated and resembles the parent normal tissue, implying that it will grow slowly
What are the characteristics of a high-grade neoplasm?
poorly differentiated and does not resemble normal tissue well, implying that it will grow more quickly than a low-grade neoplasm
How does the grade of a neoplasm affect its growth rate?
low-grade neoplasms growing slowly and high-grade neoplasms growing more quickly
What is koliocyte ?
squamous epithelial cell that has undergone a number of structural changes,
which occur as a result of infection of the cell by human papillomavirus
2 features of a koliocyte ?
- condensed chromatin
- perinuclear halo
When are people invited for colposcopy ?
if high-risk HPV and cell changes are found
What does the colposcope provide a view of ?
magnified view of the cervix and tissues to see abnormalities that are not visible to the naked eye
What is a colposcopy ?
a test to take a closer look at the cervix, further tests biopdy
Prognosis of microinvasion ?
good & treatment can be relatively conservative
Why is prognosis serious if invasion is more deep ?
likelihood of further spread increases dramatically
What is the purpose of a loop electrosurgical excision procedure (LEEP)?
to remove abnormal cells from the cervix or vagina
How does a loop electrosurgical excision procedure (LEEP) work?
a loop is heated by an electric current to function similarly to a surgical knife, allowing it to remove cells and tissues from the cervix or vagina
- loop inserted
- tissue removed from cervix
- medicine applied to reduce bleeding
What is an important aspect of cervical carcinoma ?
its prevention
List groups of people that should be vaccinated against HPV infection
- young women
- all children aged 12 to 14
- all girls under 25
- boys born after 1 September 2006
- man under 45 (GBMSM are at higher risk)
- transgender people
Why is it important to vaccinate against specific types of HPV?
some types are more likely to cause cervical cancer, so knowing about them helps target the vaccination effectively
% of oral cancers that are HPV-related in the UK ?
25 % and 35 %
Who are HPV-related oral cancers most common in ?
heterosexual men in their 40s and 50s
approximately 90% of anal cancer cases are linked to what infection ?
HPV
List risk factors for developing anal cancer
- Being over age 50
- Having another type of cancer (such as penile, cervical, vaginal or vulvar cancer)
- Having a weakened immune system (whether due to having HIV, taking certain medications or another reason)
- Regularly experiencing anal abnormalities (such as fistulas, soreness, swelling and redness)
- Having multiple sex partners
- Engaging in receptive anal sexual activity
- Smoking
What’s the most common HPV genotype detected in about 70% of anal cancers ?
HPV16
Do all HPV infections develop into anal cancer?
No, most HPV infections do not develop into anal cancer
Why is having a weakened immune system a risk factor for anal cancer?
it reduces the body’s ability to fight off HPV infections, increasing the likelihood of developing cancer
How does engaging in receptive anal sexual activity increase the risk of anal cancer?
increasing the likelihood of HPV transmission and potential infection
Anal cancer is not always linked to what ?
analreceptive intercourse
what can significantly reduce the risk of cancer development ?
early detection through screenings
What should public health initiatives focus on with HPV ?
increasing vaccination rates and awareness of HPV and its risks
Why is continued research essential with HPV ?
to fully understand the virus-cancer link and improve prevention and treatment strategies
