SN6 SHORT NOTE 5M ★ High-yield

Describe the oncogenic viruses with their associated malignancies and mechanisms.

Microbiology · 2nd Professional — Para-Clinical

Concept and Criteria

An oncogenic (tumour) virus is one capable of causing malignant transformation of cells. Viruses are implicated in roughly 15 to 20% of all human cancers, and are the second most important identifiable cause after tobacco.

Transformation is recognised in vitro by loss of contact inhibition, anchorage-independent growth, immortalisation, and the ability to form tumours in animals
Viral infection is necessary but not sufficient — most infected people never develop cancer. Cofactors and a long latent period of years to decades are the rule

Virus	Genome	Malignancy	Mechanism and cofactors
HPV 16, 18	DNA	Cervical carcinoma; anal, penile, vulval, oropharyngeal cancer	E6 inactivates p53 and E7 inactivates Rb — both tumour suppressors; smoking and immunosuppression are cofactors
Hepatitis B	DNA	Hepatocellular carcinoma	Integration into the host genome, chronic inflammation and regeneration, and the HBx protein; may cause cancer without cirrhosis. Aflatoxin and alcohol are cofactors
Hepatitis C	RNA	Hepatocellular carcinoma	Chronic inflammation and cirrhosis — it does not integrate, so cancer nearly always follows cirrhosis
EBV	DNA	Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma, post-transplant lymphoproliferative disease	Immortalises B cells; malaria is a cofactor in Burkitt lymphoma, and dietary and genetic factors in nasopharyngeal carcinoma
HHV-8	DNA	KAPOSI sarcoma; primary effusion lymphoma	Requires immunosuppression — it is an AIDS-defining malignancy
HTLV-1	RNA (retrovirus)	Adult T-cell leukaemia/lymphoma; and tropical spastic paraparesis	The Tax protein; a very long latency of decades, and a low lifetime risk
Merkel cell polyomavirus	DNA	Merkel cell carcinoma	Clonal integration
HIV	RNA (retrovirus)	Kaposi sarcoma, lymphoma, cervical cancer	Indirect — through immunosuppression permitting other oncogenic viruses, rather than by transforming cells itself

CLINICAL PEARL

HIV causes cancer without ever transforming a cell. It carries no oncogene and does not integrate near one in any consistent way. What it does is destroy the CD4 cells that normally keep HHV-8, EBV and HPV in check — so the malignancies of AIDS are almost all caused by other viruses that immune surveillance was previously containing. This is why antiretroviral therapy reduces these cancers: it restores the surveillance rather than treating the tumour.

Mechanisms of Viral Carcinogenesis

Insertion of a viral oncogene — the virus carries a gene whose product transforms the cell, as with HPV E6 and E7
Insertional mutagenesis — integration of viral DNA next to a host proto-oncogene activates it, or disrupts a tumour suppressor
Inactivation of tumour suppressors — p53 and Rb are the common targets, and it is notable that several unrelated viruses converge on the same two proteins
Chronic inflammation with regeneration — repeated cell division multiplies the chance of a mutation; this is the dominant mechanism in hepatitis C and in H. Pylori-associated gastric cancer
Immunosuppression — permitting other oncogenic viruses to escape surveillance, as in HIV and in transplantation
Inhibition of apoptosis, allowing damaged cells to survive

Prevention and Applied Aspects

Vaccination is the most powerful intervention — the hepatitis B vaccine was the first cancer vaccine, and universal infant immunisation has already reduced childhood hepatocellular carcinoma where it has been implemented; the HPV vaccine is expected to eliminate most cervical cancer
Screening — cervical cytology and HPV DNA testing; ultrasound and alpha-fetoprotein surveillance in chronic hepatitis B and C
Treating the infection prevents the cancer — direct-acting antivirals curing hepatitis C reduce hepatocellular carcinoma; suppressing hepatitis B reduces it; eradicating H. Pylori reduces gastric cancer and can cure gastric malt lymphoma outright
Reducing cofactors — alcohol, smoking, aflatoxin exposure in stored grain and groundnuts (a real problem in parts of India), and malaria control
Screening blood and organ donors for HBV, HCV, HIV and HTLV
Cervical cancer is the second commonest cancer in Indian women and is almost entirely preventable; this makes HPV vaccination and screening among the highest-value cancer interventions available in the country

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