Oral Cancer Aetiology Viruses

Question 1

What does oral cancer exclude?

Answer 1

posterior 1/3 of the tongue and soft palate because by definition they are a part of the oropharyngeal system

Question 2

what are the infectious agents-viruses?

Answer 2

• Human papilloma virus (HPV)
• Epstein-barr virus (EBV) (HHV 4)
• Human immunodeficiency virus (HIV)

Question 3

What are 5 types of HPV?

Answer 3

• Alpha
• Beta
• Gamma
• Mu
• Nu

Question 4

Describe Epidermodysplasia verruciformis or tree man illness

Answer 4

• A rare autosomal recessive genetic
• Affects your skin and increases the risk of carcinoma of the skin

Question 5

Describe Human papillomaviruses (HPVs)

Answer 5

high-risk types of HPV cause the following cancers
- cervical
- anal
- oropharyngeal
- vaginal
- vuvlar
- penile
- spread through direct sexual contact
- white, non-smoking males aged 35 to 55 are most at risk, 4 to 1 over females

Question 6

Describe HPV

Answer 6

• ds DNA circular virus
• epitheliotrophic - targets mucosa
• only 1% progress to malignant disease
• widespread in humans and other animals

Question 7

What does human papillomaviruses (HPVs) consist of?

Answer 7

• belong to the papvavirus group
• are small, non-enveloped DNA viruses of a symmetrical icosahedral shape
• Papillomavirus particles consist of a single molecule of double-stranded, circular DNA with approximately 8000 bp, contained in a capsid (spherical protein coat) composed of 72 capsomeres
• 200 types have already have identified
• HPV viruses can be grouped into high-risk (HR) and low-risk (LR) HPV types
• HR-HPVs are associated with carcinogenesis, 16,18, 31, 33, 35, 39, 45, and 52
• say high risk HPV 16 and 18 in exam

Question 8

why is HPV 16 is of interest?

Answer 8

• due to oncogenic properties
• 6 early genes (E1, E2, E4, E5, E6 AND E7)
• 2 Late genes
  (L1 and L2)
• E6 and E7 have oncogenic properties they target tumour suppressor genes

Question 9

What does HPV do?

Answer 9

• HPV infects undifferentiated proliferative basal cells, which are capable of dividing
• viral DNA localizes into the nucleus and establishes itself as an episome
• the viral proteins E1, E2, E6, and E7 are transcribed from the early promoter are expressed at a low level
• E6 and E7 may disturb the normal terminal differentiation by stimulating cellular proliferation and DNA synthesis
• the capsid proteins L1 and L2 accumulate in the mature epithelial cells
• the assembly of infectious virions takes place in terminally differentiated cells of the upper epithelial layers, and the virions are shed to the environment

Question 10

What does HPV result in?

Answer 10

• Latency and malignant transformation through interactions of viral E6 and E7 a proteins with p53 and pRB
• E7 protein binds and inactivates a human tumour suppressor gene product, the retinoblastoma protein (pRB)
• viral E6 protein binds p53 and earmarks it for destruction by the ubiquitin pathway
• During the normal HPV life cycle, viral DNA is maintained episomally in the nucleus of the affected cell, a state predominately associated with “low-risk” HPV types such as HPV-6 and -11

Question 11

describe oral HPV lesions

Answer 11

Benign
- Papilloma
- Condylomata
Malignant
- Cancer - SCC

Question 12

List risk factors

Answer 12

• Number of sexual partners
• Weakened immune systems

Question 13

HPV detection

Answer 13

• P16 staining
• In-situ hybridisation (ISH)

Question 14

List the vaccinations

Answer 14

• quadrivalent Gardasil (HVP 6, 11, 16, 18)
• bivalent Cervarix (16, 18)
• nonvalent Gardasil 9 (16, 18, 31, 33, 45, 52 and 58)

Question 15

Significance of HPV on cancer treatment outcome

Answer 15

In retrospective studies, HR-HPV - and/or p16INK4a positive tumours have been found to respond better to multimodal therapies as compared to HPV negative tumours, thereby favouring patient survival

Question 16

An explanation for the favourable response

Answer 16

• although the pRb- pathway and p53 - pathway are compromised in HPV- positive tumours, they retain some function
• presence of wild-type p53 in combination with low levels of Bcl-2/Bcl-xL and EGFR, which are features of HPV-positive tumours in non-smokers, may enhance this treatment advantage
• limited tobacco and/or alcohol use reduces field cancerisation and the chance of developing a second primary tumour or distant metastasis in HPV-positive tumours

Question 17

Describe Epstein- Barr virus (EBV)

Answer 17

• a type of herpes virus
• mononucleosis
• lymphoma
• nose and throat cancers
• transmitted by contact with saliva, sexual contact, blood transfusions, and organ transplantation
• infection is lifelong
• there is no vaccine to prevent EBV infection and no specific treatment for EBV infection
• the human herpes virus family consists of three subfamilies, i.e. alpha, beta and gamma
• EBV belongs to the gamma subfamily, which is split into two, lymphocryptovirus and rhadinovirus
• it latently infects B-lymphocytes
• EBV has a toroid-shaped protein core, wrapped with DNA; a nucleocapsid with 162 capsomeres; a protein tegument between the nucleocapsid and the envelope; and an outer envelope with external glycoprotein spikes
• genome in the form of a linear, double-stranded, 172 kbp DNA molecule

Question 18

describe human immunodeficiency virus (HIV)

Answer 18

• acquired immunodeficiency syndrome (AIDS)
• infection with HIV weakens the immune system and makes the body less able to fight off other infections that cause cancer
• increased risks of kaposi sarcoma, lymphomas (including both r Hodgkin lymphoma and Hodgkin disease), and cancers of the cervix, anus, lung, liver, and throat
• transmitted via blood and through sexual contact and share needles
• Oral symptoms include candidiasis, hairy leukoplakia, accelerate periodontal disease, Kaposis’s sarcoma, salivary gland disease, oral ulcers

Question 19

What is HIV treatment?

Answer 19

• highly effective antiviral treatment (HAART)

Question 20

describe kaposi sarcoma-associated herpesvirus (KSHV)

Answer 20

• Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 IHHV-8), can cause Kaposi sarcoma. KSHV can also cause primary effusion lymphoma and multicentric castleman disease
• KSHV is most commonly spread through saliva. It can also be spread through organ or bone marrow transplantation, and there is some evidence that it can be spread by blood transfusion
• there is no vaccine to prevent KSHV infection and no therapy to treat infection
• people who are infected with HIV can lower their risk of KSHV- related complications by using antiretroviral therapy
• kaposi’s sarcoma is a rare type of cancer that affects the skin, mouth and occasionally the internal organs
• the first symptoms of Kaposi’s sarcoma are usually red, purple, or brown patches, plaques or nodules on the skin (the abnormal growth of small blood vessels just below the skin gives the lesions their purplish hue)

Question 21

Answer 21