{"entity":{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","aka":[],"tldr":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Oncovirus","links":[{"label":"Mesri, Feitelson & Munger, Human viral oncogenesis: a cancer hallmarks analysis (Cell Host Microbe 2014)","url":"https://doi.org/10.1016/j.chom.2014.02.011"},{"label":"IARC Monographs, biological agents (volume 100B)","url":"https://publications.iarc.fr/119"},{"label":"Young and Rickinson, Nat Rev Cancer 2004: Epstein-Barr virus, 40 years on","url":"https://doi.org/10.1038/nrc1452"},{"label":"Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases","url":"https://doi.org/10.1038/ng.3415"}],"tags":["mechanism","mechanics-atlas"],"related":[],"cancers":["cervical","head-and-neck","nasopharyngeal","hcc","merkel-cell-carcinoma","kaposi-sarcoma","anal","hodgkin-lymphoma","non-hodgkin-lymphoma","peripheral-t-cell-lymphoma","burkitt-lymphoma"],"sections":[],"technologies":["hpv-vaccine","hpv-testing","colposcopy-excision","cthpv-dna","hcc-surveillance","tcr-t"],"targets":["tp53","cdk4-6","pd1","pdl1"],"drugs":["gardasil-9","avelumab","retifanlimab","pembrolizumab","cemiplimab"],"companies":[],"institutions":[],"pathways":["inflammation-nfkb","p53-mdm2-axis","p53-cell-cycle","antigen-presentation-immunoediting"],"terms":["hpv-p16","hbv-hcv","plasma-ebv-dna","cin-hsil","tumor-promoting-inflammation","lymphoma-bio-ebv-latency","lymphoma-bio-htlv1"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mesri-cell-host-microbe"],"journals":[],"dependsOn":[],"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)."],"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.","nodes":[{"id":"hpv","label":"HPV E6 / E7","x":12,"y":15},{"id":"ebv","label":"EBV LMP1, EBNA","x":12,"y":45},{"id":"hbv","label":"HBV / HCV","x":12,"y":78},{"id":"p53","label":"p53 degraded","x":45,"y":8,"targetId":"tp53"},{"id":"rb","label":"RB inactivated","x":45,"y":30,"targetId":"cdk4-6"},{"id":"nfkb","label":"NF-κB, immortalisation","x":45,"y":52},{"id":"infl","label":"Chronic inflammation, cirrhosis","x":45,"y":78},{"id":"ca","label":"Virus-driven cancer","x":80,"y":45},{"id":"ag","label":"Viral antigens → IO response","x":80,"y":80,"targetId":"pd1"},{"id":"vax","label":"Vaccination, antivirals","x":80,"y":12}],"edges":[{"from":"hpv","to":"p53","type":"activates"},{"from":"hpv","to":"rb","type":"activates"},{"from":"ebv","to":"nfkb","type":"activates"},{"from":"hbv","to":"infl","type":"activates"},{"from":"p53","to":"ca","type":"activates"},{"from":"rb","to":"ca","type":"activates"},{"from":"nfkb","to":"ca","type":"activates"},{"from":"infl","to":"ca","type":"activates"},{"from":"ca","to":"ag","type":"activates"},{"from":"vax","to":"hpv","type":"inhibits"},{"from":"vax","to":"hbv","type":"inhibits"}],"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"]},"route":"/pathways/oncogenic-viruses/","neighbours":{"cancer":[{"id":"adult-t-cell-leukaemia-lymphoma","kind":"cancer","name":"Adult T-cell leukaemia/lymphoma","route":"/cancers/adult-t-cell-leukaemia-lymphoma/"},{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"ebv-positive-dlbcl","kind":"cancer","name":"EBV-positive diffuse large B-cell lymphoma","route":"/cancers/ebv-positive-dlbcl/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"kaposi-sarcoma","kind":"cancer","name":"Kaposi sarcoma","route":"/cancers/kaposi-sarcoma/"},{"id":"merkel-cell-carcinoma","kind":"cancer","name":"Merkel cell carcinoma","route":"/cancers/merkel-cell-carcinoma/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"penile","kind":"cancer","name":"Penile cancer","route":"/cancers/penile/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","route":"/cancers/post-transplant-lymphoproliferative-disorder/"},{"id":"primary-effusion-lymphoma","kind":"cancer","name":"Primary effusion lymphoma","route":"/cancers/primary-effusion-lymphoma/"},{"id":"urethral","kind":"cancer","name":"Urethral cancer","route":"/cancers/urethral/"},{"id":"vaginal","kind":"cancer","name":"Vaginal cancer","route":"/cancers/vaginal/"}],"technology":[{"id":"cthpv-dna","kind":"technology","name":"Circulating tumour HPV DNA (ctHPV-DNA)","route":"/technologies/cthpv-dna/"},{"id":"colposcopy-excision","kind":"technology","name":"Colposcopy and excisional treatment (LEEP/LLETZ, cone)","route":"/technologies/colposcopy-excision/"},{"id":"hcc-surveillance","kind":"technology","name":"HCC surveillance in cirrhosis (ultrasound + AFP)","route":"/technologies/hcc-surveillance/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"hpv-testing","kind":"technology","name":"HPV DNA testing and self-sampling","route":"/technologies/hpv-testing/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"card11","kind":"target","name":"CARD11","route":"/targets/card11/"},{"id":"ccr4","kind":"target","name":"CCR4","route":"/targets/ccr4/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"irf4","kind":"target","name":"IRF4","route":"/targets/irf4/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"plcg1","kind":"target","name":"PLCG1","route":"/targets/plcg1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"},{"id":"vav1","kind":"target","name":"VAV1","route":"/targets/vav1/"}],"drug":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"gardasil-9","kind":"drug","name":"Nonavalent HPV vaccine","route":"/drugs/gardasil-9/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"retifanlimab","kind":"drug","name":"Retifanlimab","route":"/drugs/retifanlimab/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"p53-mdm2-axis","kind":"pathway","name":"The p53 network (guardian of the genome)","route":"/pathways/p53-mdm2-axis/"}],"term":[{"id":"cin-hsil","kind":"term","name":"Cervical precancer (CIN, HSIL/LSIL)","route":"/terms/cin-hsil/"},{"id":"tumor-promoting-inflammation","kind":"term","name":"Enabling characteristic: tumour-promoting inflammation","route":"/terms/tumor-promoting-inflammation/"},{"id":"lymphoma-bio-ebv-latency","kind":"term","name":"Epstein-Barr virus latency programmes, and why they decide which lymphoma","route":"/terms/lymphoma-bio-ebv-latency/"},{"id":"hbv-hcv","kind":"term","name":"Hepatitis B and C as cancer causes","route":"/terms/hbv-hcv/"},{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","route":"/terms/hpv-p16/"},{"id":"lymphoma-htlv-1","kind":"term","name":"HTLV-1 (human T-lymphotropic virus type 1)","route":"/terms/lymphoma-htlv-1/"},{"id":"lymphoma-bio-htlv1","kind":"term","name":"HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma","route":"/terms/lymphoma-bio-htlv1/"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"},{"id":"plasma-ebv-dna","kind":"term","name":"Plasma EBV DNA","route":"/terms/plasma-ebv-dna/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"}],"paper":[{"id":"paper-mesri-cell-host-microbe","kind":"paper","name":"Human viral oncogenesis: a cancer hallmarks analysis","route":"/key-papers/paper-mesri-cell-host-microbe/"}],"trial":[{"id":"javelin-merkel-200","kind":"trial","name":"JAVELIN Merkel 200","route":"/trials/javelin-merkel-200/"},{"id":"keynote-017","kind":"trial","name":"KEYNOTE-017 (Cancer Immunotherapy Trials Network 09)","route":"/trials/keynote-017/"}]}}