Aetiology - viruses Flashcards
what are causes of oral cancer?
tobacco, alcohol, HPV, poor nutrition, UV light, immunocompromise, genetic, potentially malignant conditions
describe the structure of HPV
double stranded DNA
circular
small
non-enveloped
capsid
72 capsomeres
what does HPV target?
mucosa
what are the types of HPV?
Alpha
beta
gamma
Mu
Nu
what are high risk HPV types associated with carncinogens?
16 and 18
what does HPV 16 target?
tumorous suppressor genes E6+7
what types of cells does HPV16 infect?
undifferentiated proliferative basal cells capable of dividing
what is an episome?
when DNA localises into the nucleus
with HPV16 infection, what viral proteins are transcribed from the early promotor?
E1,2,6,7
what do E6+7 do in HPV infection?
disturb the normal terminal differentiation by stimulating cellular proliferation and DNA synthesis
where do capsid proteins L1 and 2 accumulate during HPV infection?
mature epithelial cells
where does assembly of infectious virions take place?
terminally differentiated cells of upper epithelial layers
what is an epidermodysplasia verruciformis?
exuberant growth by HPV
rare autosomal recessive genetic condition that effects skin and increases the risk of carcinoma of the skin
what is a papilloma?
harmless/ benign
common on soft palate
small raised white lesion
how would you treat a papilloma?
X vision
what types of cancers may high risk HPV cause?
cervical, anal, oropharyngeal, vaginal, vulvar, penile
how are most oropharyngeal cancers spread?
sexual contact
who are most at risk of HPV cancers?
white, non-smoking males aged 35 to 55
where is HPV associated oropharyngeal cancer commonly seen?
base of tongue and tonsillar bed
how may HPV infection result in latency and malignant transformation?
interactions of E6 and E7 with p53 and PrB.
where is DNA kept during the normal HPV cycle?
episomally in the nucleus of affected cell
,what are low risk HPV types?
6 and 11
where does the HPV lifecyle start?
basement membrane
in the HPV lifecycle, where do mutagenic changes occur?
stratum spinosium
what is angiogenesis?
formation of new blood vessels
what are the differences between low risk and high risk HPV?
low risk doesn’t have:
E6 products that knock out tumour suppressor genes
no binding of PdX protein domains (doesn’t inhibit apoptosis)
after infection of low risk you don’t get bypass of growth arrest, i.e., weaker inhibition of interferon response.
what are the 2 types of benign oral HPV lesions?
papilloma
condylomata
describe an oral papilloma
layers of finger like projections
where would you find oral papillomas?
soft palate
are oral papillomas high or low risk?
low
transmission of oral papilloma?
sexual contact
what are the types of malignant oral HPV lesions?
keratinised lesion on ventral tongue
SCC mucosa of gingivae surrounding teeth
keratotic attached gingivae
mixed red/white indurated alveolar surrounding teeth
what makes the lingual gutter a high risk site?
saliva pools and if contained carcinogens from tobacco and alcohol it will be in direct contact with mucosa
why may a SCC of gingivae be mistaken for perio disease?
mobile teeth
what does indurated mean?
hard and rubbery
what does exophytic mean?
growing out the way
what does endophytic mean?
breaks down underlying structure
what are HPV risk factors?
high number of sexual partners
weakened immune system
what are the 2 HPV detection methods?
p16 staining
in-situ hybridisation
how does p16 staining work?
looks for p16 protein down streaming of p53 and retinoblastoma gene (when these 2 genes are targeted by HPV, there is an increase in p16 expression)
how does in-situ hybridisation work?
looks for HPV RNA/DNA in cells (dark brown staining within epithelial cells
what are the 3 vaccines for HPV
Quadrivalent Gardasil
Bivalent Cervarix
Nonvalent Gardasil
what types of HPV is quadrivalent gardasil for?
6 11 16 18
what types of HPV is Bivalent cervarix for?
16 18
what types of HPV is nonvalent gardasil for?
16 18 31 33 45 52 58
what are low risk HPV types?
6 11
genital warts, papillomas
what are high risk HPV types?
16 18
mouth cancer
what is EPV?
a type of herpes
what can EBV present as?
- Mononucleosis
- Lymphoma
- Nose and throat cancers
how is EBV transmitted?
saliva
sexual
blood transfusions
organ transplantation
what are the 3 herpes subfamilies?
alpha
beta
gamma
what is EBV categorised in to?
lymphocryptovirus
Rhadinovirus
what does EBV infect?
B-lymphocytes
features of EBV?
- Toroid-shaped protein core, wrapped in DNA.
- Nucleocapsid with 162 capsomeres.
- Protein tegument between nucleocapsid and envelope.
- Outer envelope with external glycoprotein spikes.
What is the common impact of EBV in african countries?
direct impact on the nasopharynx causing a tumour called nasopharyngeal carcinoma
what does EBV in mononucleic form cause?
glandular fever
what are symptoms of glandular fever?
- Lymphadenopathy (enlargement of tonsillar bed)
- Sore throat
- Hepatomegaly and splenomegaly
- Rash
what is Burkitt’s lymphoma?
cancer of nasopharynx associated with EBV
what does HIV increase risk of?
- Kaposi sarcoma
- Lymphomas
- Cancers of cervix, anus, lungs, liver, and throat
how is HIV transmitted?
blood
sexual
what are oral symptoms of HIV?
- Candidiasis
- Hairy leucoplakia (unusual white patch)
- Accelerated periodontal disease.
- Kaposis’s sarcoma
- Salivary gland disease
- Oral ulcers
Who is at risk of HIV?
- Men who have unprotected sex with other men.
- People who share needles for drug injection
- Heterosexual individuals who have unprotected sex with multiple partners
how is HIV treated?
HAART
what is human herpesvirus - 8?
kaposi sarcoma- associated herpesvirus
what can KSHV cause?
Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease
how may people with HIV lower their risks of KSHV complications?
antiviral therapy
what is kaposi sarcoma?
rare type of cancer that affects skin mouth and internal organs
what causes kaposi sarcoma?
HHV-8 and HIV infection
symptoms of kaposi sarcoma?
- Red, purple, or brown patches.
- Plaques, or nodules on skin.
what gives lesions purplish blue colour?
Abnormal growth of small blood vessels just below skin
