Wednesday, August 31, 2011

Role of viruses and vaccines in head and neck malignancies

Oncovirus is a virus that causes cancer. Majority of viruses dont cause tumors due to their long evolutional history and coexistance with the human host. It has been estimated that about 20% of all malignant lesions are caused by oncogenic viruses. These oncogenic viruses can either be a RNA virus or DNA virus. Oncogenic tumors can hence be prevented by developing vaccines against appropriate oncoviruses.

Characteristics of oncogenic viruses:

1. The oncogenic viruses doesn't obey Koch's postulates
2. These viruses cause little or no symptoms after infection
3. Oncoviruses can either be DNA virus or RNA virus

Bradford Hill criteria is usually used to ascertain the association between oncogenic viruses and causation of tumors since oncogenic viruses don't fullfill Koch's criteria.

Hill criteria:

1. Strength – Also known as strength of assoication. A small association doesn't mean that it is not a causal effect. Larger the association more likely it is to be causal.
2. Consistency – Consistent findings observed by different examiners from different locations strengthens the likelihood of causal effect
3. Specificity – More specific the association between a factor and an effect the higher the probablity of causal relationship
4. Temporality – The effect has to occur after the cause
5. Biological gradient – Greater exposure leads to greater incidence of the effect
6. Plausibility – Plausible mechanism between cause and effect is helpful
7. Coherence – Between epidemiological and laboratory findings increases the likelihood of the effect
8. Experiment – If possible experimental evidence should be sought
9. Analogy – Effect of similar factors should always be considered

Classification of oncoviruses:

1. Viruses with DNA genome – Adenoviruses
2. Viruses with RNA genome – Hepatitis C virus
3. Retroviruses having both DNA and RNA genome – Human T lymphotrophic virus / Hepatitis B virus
4. Viruses that present as Eisomes / plasmids with an ability to replicate separately from host cell DNA e.g. Epstein Barr virus and Kaposi sarcoma associated herpes virus.

Mechanism of viral tumerogenecity:

1. Direct mechanism which involves insertion of oncogenetic material to the host cell
2. Enhancing already present oncogenetic genes (proto oncogenes) in the genome

Direct tumor viruses should atleast have one virus copy in each tumor cell. This viral genome is capable of expressing atleast one protein / RNA. These cells express surface viral antigens to which immune mechanism can be sensitized. In normal individuals the immune mechanism is capable of destroying these cells in a targetted manner. These type of viruses hence commonly cause tumors in patients who are immunosuppressed.

Common viruses causing Head and Neck malignancies:

1. Human papilloma viruses (Squamous cell carcinoma of oropharynx)
2. Epstein Barr virus (Nasopharyngeal carcinoma)
3. Kaposi sarcoma associated Herpes virus (Kaposi sarcoma)

Role of vaccines in preventing virus induced head and neck malignancies:

Most commonly available vaccine is HPV vaccine (Human Papilloma virus vaccine). It is of two types containing serotypes 16 and 18.

Hepatitis B and Hepatitis C vaccines are also commonly used to prevent Hepatitis B and C infections.

Another vaccine which is undergoing extensive clinical trial is the Epstein Barr virus vaccine. This again holds much promise.

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