Oncogenic Viruses and Microbes
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Direct answer
Epstein-Barr virus was the first virus convincingly linked to a human tumour when Denis Burkitt mapped the geographic distribution of the childhood lymphoma bearing his name, and EBV remains the exam's richest oncogenic virus — causing Burkitt lymphoma, nasopharyngeal carcinoma, a share of Hodgkin lymphoma, and post-transplant lymphoproliferative disease. HPV drives cervical and oropharyngeal carcinoma by disabling both guardian genes (E6 degrades p53, E7 disables Rb), while hepatitis B and C, HHV-8, HTLV-1 and Merkel cell polyomavirus complete the viral list, with Helicobacter pylori the chief bacterial contributor via gastric MALT lymphoma and adenocarcinoma. Understanding the mechanism (latent episomal expression, chronic inflammation, or immune suppression) explains both the latency and the prevention strategy.
What you must remember
- HPV high-risk types 16 and 18 express E6 (ubiquitin-mediated degradation of p53) and E7 (inactivation of Rb) — the two hits delivered by one virus; E7 releases E2F, and integration into the host genome marks progression from CIN to carcinoma.
- HPV vaccination under India's immunisation programme now targets cervical cancer prevention; vaccination prevents infection but treats nothing.
- EBV infects B cells via CD21 (CR2), expresses latent genes including LMP-1 (a constitutive CD40 mimic driving survival) and EBNA; associated tumours are Burkitt lymphoma (endemic, MYC-driven — EBV is a co-factor), nasopharyngeal carcinoma (undifferentiated type, commonest in southern China), Hodgkin lymphoma (a subset), post-transplant lymphoproliferative disorder (driven by immunosuppression), and NK/T-cell lymphoma.
- HHV-8 (Kaposi sarcoma-associated herpesvirus) causes Kaposi sarcoma, the classic AIDS-defining vascular tumour of skin and viscera, especially when CD4 counts fall.
- HTLV-1 causes adult T-cell leukaemia/lymphoma after decades of latency, with flower cells on smear and hypercalcaemia; transmission is vertical, sexual and by blood.
- Hepatitis B and C cause hepatocellular carcinoma largely through chronic inflammation, regeneration and oxidative damage rather than direct viral oncogenes; HBV vaccination is the first vaccine proven to prevent a human cancer.
- Merkel cell polyomavirus contributes to Merkel cell carcinoma of skin in the elderly and immunosuppressed.
- Helicobacter pylori, CagA-positive strains, drive gastric adenocarcinoma (Correa sequence) and gastric MALT lymphoma — the clearest bacterium-cancer link and reversible at the lymphoma stage by eradication.
- Immunosuppression unmasking viral oncogenesis: post-transplant lymphoproliferative disorder and AIDS-related lymphomas; reducing immunosuppression can regress PTLD.
How to work through a virus-tumour question
A 40-year-old from southern India with nasal obstruction, epistaxis and a cervical node: biopsy of the nasopharyngeal mass shows undifferentiated carcinoma infiltrated by lymphocytes, with high IgA antibodies to EBV capsid antigen. Undifferentiated nasopharyngeal carcinoma is EBV-associated in nearly all cases, with clonal viral genomes and LMP-1 expression in tumour nuclei; the virus acts together with dietary cofactors such as nitrosamines in preserved fish.
Now a woman with postcoital bleeding and a high-grade cervical intraepithelial lesion, clonal and HPV-16 positive: E6 has degraded p53 and E7 has freed E2F from Rb. Integration of viral DNA disrupts E2, which normally represses E6/E7 transcription — integration, not mere infection, marks the high-grade step. Pap smear detects the precursor and HPV DNA testing sharpens it; prevention is prophylactic vaccination plus screening.
Finally, a renal transplant patient on tacrolimus develops a polymorphic EBV-positive B-cell proliferation — post-transplant lymphoproliferative disorder — where reducing immunosuppression, not immediate chemotherapy, is the first move, illustrating that viral oncogenesis is a dance between microbe and host immunity.
Where students slip
The commonest error is assigning Burkitt lymphoma wholly to EBV: endemic (African) Burkitt is nearly always EBV-positive, but sporadic Burkitt is usually EBV-negative — the constant in all variants is MYC dysregulation from the immunoglobulin-heavy-chain translocation. Second, candidates mix up the HPV oncoproteins' targets: E6 attacks p53 and E7 attacks Rb; a memory hook is that the numbers pair in order — E6 with p53 does not rhyme, so instead anchor on "E7 loves Rb" (both contain seven letters... or simply recall E6 degrades, E7 disables). Third, remember that hepatitis viruses cause cancer through chronic inflammation and cirrhosis, without viral oncogenes, which is why the risk falls with antiviral suppression and why HBV vaccine prevents cancer. Finally, Kaposi sarcoma in a young man is a sentinel for HIV in the Indian exam setting — order the HIV test.
Frequently asked questions
Which HPV oncoproteins disable which tumour suppressors?
E6 ubiquitinates and degrades p53 while E7 binds and inactivates Rb, releasing E2F and driving S-phase entry.
Which tumour was first linked to Epstein-Barr virus and what is its signature translocation?
Endemic Burkitt lymphoma of African children, carrying t(8;14) with MYC dysregulation; EBV acts as a co-factor rather than the sole driver.
Which virus causes adult T-cell leukaemia/lymphoma and what cell is seen on the smear?
HTLV-1, producing flower cells (pleomorphic lobated lymphocytes), often with hypercalcaemia and skin lesions after decades of latency.
How do hepatitis B and C cause hepatocellular carcinoma without viral oncogenes?
Through chronic hepatocyte death and regeneration with oxidative DNA damage and fibrosis, making cirrhosis the strongest risk state.
Which bacterium causes two distinct gastric malignancies?
Helicobacter pylori — gastric adenocarcinoma through the Correa sequence and gastric MALT lymphoma, which can regress with eradication therapy.
What is post-transplant lymphoproliferative disorder and its first-line management?
An EBV-driven B-cell proliferation under iatrogenic immunosuppression, treated initially by reducing immunosuppression, with rituximab or chemotherapy reserved for progression.