# Oncogenic viruses

Source: https://onco.cc/pathways/oncogenic-viruses/  
OnCo record `oncogenic-viruses` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

About one cancer in eight worldwide is caused by a virus. HPV, hepatitis B and C, Epstein-Barr, HTLV-1, KSHV and Merkel cell polyomavirus each hijack the same brakes cancer normally has to mutate, which is why vaccines against HPV and HBV are among the most effective anti-cancer drugs ever made.

## Summary

Direct carcinogens express viral oncoproteins: HPV E6 degrades p53 and E7 inactivates RB (cervical, anal, oropharyngeal; p16 overexpression is the surrogate); EBV LMP1 mimics CD40 to drive NF-κB and EBNA proteins immortalise B cells (nasopharyngeal, Burkitt, Hodgkin, post-transplant lymphoma; plasma EBV DNA is a biomarker); HTLV-1 Tax/HBZ (adult T-cell leukaemia); KSHV vFLIP/vCyclin (Kaposi sarcoma); MCPyV truncated large T antigen (Merkel cell). Indirect carcinogens act via chronic inflammation and regeneration: HBV (also integrates and expresses HBx) and HCV cause cirrhosis and HCC; H. pylori (a bacterium) drives gastric cancer via CagA and inflammation. Virus-driven tumours carry foreign antigens, explaining high immunotherapy response in Merkel cell carcinoma and HPV+ head and neck cancer, and enabling viral-antigen TCR-T and vaccines. Prevention: HPV (Gardasil 9) and HBV vaccination, HCV cure with direct-acting antivirals, H. pylori eradication.

## Fields

- Kind: Pathway
- Last checked: 2026-09-09
- Tags: mechanism; mechanics-atlas
- Analogy: A burglar who does not need to pick the locks because he carries a master key: E6 and E7 are keys that open p53 and RB directly, saving the virus the years of mutation a spontaneous cancer needs. The upside is that the burglar's face is on every camera, so the immune system can be taught to spot him.
- Interventions: HPV vaccination (Gardasil 9) and HBV vaccination prevent the infection; HCV direct-acting antivirals and H. pylori eradication remove the driver; HPV testing and colposcopy find and excise precursor lesions; Checkpoint inhibitors work well in Merkel cell (avelumab, retifanlimab) and HPV+ cancers; EBV- and HPV-specific TCR-T and vaccines are in trials; Plasma EBV DNA screens for nasopharyngeal carcinoma and tracks response

## Notes

- Lymphoma: two viruses, two mechanisms. Epstein-Barr virus causes different diseases depending on which latency programme the infected cell runs, from EBNA1 alone in Burkitt lymphoma to the full set in post-transplant disease, and the programme tracks how closely T cells are watching (Young and Rickinson 2004). HTLV-1 works by starting a process the host genome then finishes along the lines the virus drew: across 426 adult T-cell leukaemia/lymphoma cases, the acquired alterations overlapped significantly with the Tax interactome and concentrated in T-cell receptor and NF-kB signalling, trafficking and immune surveillance (Kataoka 2015).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Oncovirus
- Mesri, Feitelson & Munger, Human viral oncogenesis: a cancer hallmarks analysis (Cell Host Microbe 2014): https://doi.org/10.1016/j.chom.2014.02.011
- IARC Monographs, biological agents (volume 100B): https://publications.iarc.fr/119
- Young and Rickinson, Nat Rev Cancer 2004: Epstein-Barr virus, 40 years on: https://doi.org/10.1038/nrc1452
- Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases: https://doi.org/10.1038/ng.3415

## Connected records

- cancers: [Adult T-cell leukaemia/lymphoma](https://onco.cc/cancers/adult-t-cell-leukaemia-lymphoma/), [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Cervical cancer](https://onco.cc/cancers/cervical/), [EBV-positive diffuse large B-cell lymphoma](https://onco.cc/cancers/ebv-positive-dlbcl/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Kaposi sarcoma](https://onco.cc/cancers/kaposi-sarcoma/), [Merkel cell carcinoma](https://onco.cc/cancers/merkel-cell-carcinoma/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Penile cancer](https://onco.cc/cancers/penile/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/), [Primary effusion lymphoma](https://onco.cc/cancers/primary-effusion-lymphoma/), [Urethral cancer](https://onco.cc/cancers/urethral/), [Vaginal cancer](https://onco.cc/cancers/vaginal/)
- technologies: [Circulating tumour HPV DNA (ctHPV-DNA)](https://onco.cc/technologies/cthpv-dna/), [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [HCC surveillance in cirrhosis (ultrasound + AFP)](https://onco.cc/technologies/hcc-surveillance/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/)
- targets: [CARD11](https://onco.cc/targets/card11/), [CCR4](https://onco.cc/targets/ccr4/), [CD30](https://onco.cc/targets/cd30/), [CDK4/6](https://onco.cc/targets/cdk4-6/), [IRF4](https://onco.cc/targets/irf4/), [MYC](https://onco.cc/targets/myc-gene/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [PLCG1](https://onco.cc/targets/plcg1/), [TP53](https://onco.cc/targets/tp53/), [VAV1](https://onco.cc/targets/vav1/)
- drugs: [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Retifanlimab](https://onco.cc/drugs/retifanlimab/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [Cervical precancer (CIN, HSIL/LSIL)](https://onco.cc/terms/cin-hsil/), [Enabling characteristic: tumour-promoting inflammation](https://onco.cc/terms/tumor-promoting-inflammation/), [Epstein-Barr virus latency programmes, and why they decide which lymphoma](https://onco.cc/terms/lymphoma-bio-ebv-latency/), [Hepatitis B and C as cancer causes](https://onco.cc/terms/hbv-hcv/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/), [HTLV-1 (human T-lymphotropic virus type 1)](https://onco.cc/terms/lymphoma-htlv-1/), [HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma](https://onco.cc/terms/lymphoma-bio-htlv1/), [Microenvironment and inflammation: tumours as wounds that do not heal](https://onco.cc/terms/microenvironment-inflammation-theory/), [Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/)
- key papers: [Human viral oncogenesis: a cancer hallmarks analysis](https://onco.cc/key-papers/paper-mesri-cell-host-microbe/)
- trials: [JAVELIN Merkel 200](https://onco.cc/trials/javelin-merkel-200/), [KEYNOTE-017 (Cancer Immunotherapy Trials Network 09)](https://onco.cc/trials/keynote-017/)

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