types are carcinogenic. hepatitis b virus (hbv) is associated with hepatocarcinoma epstein–barr virus (ebv or hhv-4) is associated with four types of cancers human cytomegalovirus (cmv or hhv-5) is associated with mucoepidermoid carcinoma and possibly other malignancies. kaposi's sarcoma-associated herpesvirus (kshv or hhv-8) is associated with kaposi's sarcoma, a type of skin cancer. merkel cell polyomavirus – a polyoma virus – is associated with the development of merkel cell carcinoma rna viruses not all oncoviruses are dna viruses. some rna viruses have also been associated such as the hepatitis c virus as well as certain retroviruses, e.g., human t-lymphotropic virus (htlv-1) and rous sarcoma virus (rsv). overview table virus percent of cancers associated cancer types hepatitis b virus (hbv)hepatocarcinoma hepatitis c virus (hcv)hcv is a known carcinogen, causing hepatocarcinoma human t-lymphotropic virus (htlv)0.03adult t-cell leukemia human papillomaviruses (hpv)5.2hpv types 16 and 18 are associated with cancers of cervix, anus, penis, vulva, vagina, and hpv-positive oropharyngeal cancers. according to statistics in the united states, females are more impacted by hpv-associated cancers (83%) than males (74%). kaposi's sarcoma-associated herpesvirus (hhv-8)0.9kaposi's sarcoma, multicentric castleman's disease and primary effusion lymphoma merkel cell polyomavirus (mcv)namerkel cell carcinoma epstein–barr virus (ebv)naburkitt's lymphoma, hodgkin's lymphoma, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma and a subtype of stomach cancer. estimated percent of new cancers attributable to the virus worldwide in 2002. na indicates not available. the association of other viruses with human cancer is continually under research. main viruses associated with human cancer major capsid protein l1 pentamer, human papillomavirus 11 the structure of the hepatitis b virus the main viruses associated with human cancers are the human papillomavirus, the hepatitis b and hepatitis c viruses, the epstein–barr virus, the human t-lymphotropic virus, the kaposi's sarcoma-associated herpesvirus (kshv) and the merkel cell polyomavirus. experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. the mode of virally induced tumors can be divided into two, acutely transforming or slowly transforming. in acutely transforming viruses, the viral particles carry a gene that encodes for an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. in contrast, in slowly transforming viruses, the virus genome is inserted, especially as viral genome insertion is an obligatory part of retroviruses, near a proto-oncogene in the host genome. the viral promoter or other transcription regulation elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly transforming viruses have very long tumor latency compared to acutely transforming viruses, which already carry the viral oncogene. hepatitis viruses, including hepatitis b and hepatitis c, can induce a chronic viral infection that leads to liver cancer in 0.47% of hepatitis b patients per year (especially in asia, less so in north america), and in 1.4% of hepatitis c carriers per year. liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease. through advances in cancer research, vaccines designed to prevent cancer have been created. the hepatitis b vaccine is the first vaccine that has been established to prevent cancer (hepatocellular carcinoma) by preventing infection with the causative virus. in 2006, the u.s. food and drug administration approved a human papilloma virus vaccine, called gardasil. the vaccine protects against four hpv types, which together cause 70% of cervical cancers and 90% of genital warts. in march 2007, the us centers for disease control and prevention (cdc) advisory committee on immunization practices (acip) officially recommended that females aged 11–12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization. history the history of cancer virus discovery is intertwined with the history of cancer research and the history of virology. the oldest surviving record of a human cancer is the babylonian code of hammurabi (dated ca. 1754 bc) but scientific oncology could only emerge in the 19th century, when tumors were studied at microscopic level with the help of the compound microscope and achromatic lenses. 19th century microbiology accumulated evidence that implicated bacteria, yeasts, fungi, and protozoa in the development of cancer. in 1926 the nobel prize was awarded for documenting that a nematode worm could provoke stomach cancer in rats. but it was not recognized that cancer could have infectious origins until much later as virus had first been discovered by dmitri ivanovsky and martinus beijerinck at the close of the 19th century. history of non-human oncoviruses rabbit with shope papilloma virus infection. the theory that cancer could be caused by a virus began with the experiments of oluf bang and vilhelm ellerman in 1908 at the university of copenhagen. bang and ellerman demonstrated that avian sarcoma leukosis virus could be transmitted between chickens after cell-free filtration and subsequently cause leukemia. this was subsequently confirmed for solid tumors in chickens in 1910–1911 by peyton rous. rous at the rockefeller university extended bang and ellerman's experiments to show cell-free transmission of a solid tumor sarcoma to chickens (now known as rous sarcoma). the reasons why chickens are so receptive to such transmission may involve unusual characteristics of stability or instability as they relate to endogenous retroviruses. charlotte friend confirmed bang and ellerman findings for liquid tumor in mice by . in 1933 richard shope and edward weston hurst showed that warts from wild cottontail rabbits contained the shope papilloma virus. in 1936 john joseph bittner identified the mouse mammary tumor virus, an "extrachromosomal factor" (i.e. virus) that could be transmitted between laboratory strains of mice by breast feeding. by the early 1950s, it was known that viruses could remove and incorporate genes and genetic material in cells. it was suggested that such types of viruses could cause cancer by introducing new genes into the genome. genetic analysis of mice infected with friend virus confirmed that retroviral integration could disrupt tumor suppressor genes, causing cancer. viral oncogenes were subsequently discovered and identified to cause cancer. ludwik gross identified the first mouse leukemia virus (murine leukemia virus) in 1951 and in 1953 reported on a component of mouse leukemia extract capable of causing solid tumors in mice. this compound was subsequently identified as a virus by sarah stewart and bernice eddy at the national cancer institute, after whom it was once called "se polyoma". in 1957 charlotte friend discovered the friend virus, a strain of murine leukemia virus capable of causing cancers in immunocompetent mice. though her findings received significant backlash, they were eventually accepted by the field and cemented the validity of viral oncogenesis. in 1961 eddy discovered the simian vacuolating virus 40 (sv40). merck laboratory also confirmed the existence of a rhesus macaque virus contaminating cells used to make salk and sabin polio vaccines. several years later, it was shown to cause cancer in syrian hamsters, raising concern about possible human health implications. scientific consensus now strongly agrees that this is not likely to cause human cancer. history of human oncoviruses in 1964 anthony epstein, bert achong and yvonne barr identified the first human oncovirus from burkitt's lymphoma cells. a herpesvirus, this virus is formally known as human herpesvirus 4 but more commonly called epstein–barr virus or ebv. in the mid-1960s baruch blumberg first physically isolated and characterized hepatitis b while working at the national institute of health (nih) and later the fox chase cancer center. although this agent was the clear cause of hepatitis and might contribute to liver cancer hepatocellular carcinoma, this link was not firmly established until epidemiologic studies were performed in the 1980s by r. palmer beasley and others. in 1980 the first human retrovirus, human t-lymphotropic virus 1 (htlv-i), was discovered by bernard poiesz and robert gallo at nih, and independently by mitsuaki yoshida and coworkers in japan. but it was not certain whether htlv-i promoted leukemia. in 1981 yorio hinuma and his colleagues at kyoto university reported visualization of retroviral particles produced by a leukemia cell line derived from patients with adult t-cell leukemia/lymphoma. this virus turned out to be htlv-1 and the research established the causal role of the htlv-1 virus to atl. nobel prize in physiology or medicine 2020: seminal experiments by harvey j. alter, michael houghton and charles m. rice leading to the discovery of hcv as the causative agent of non-a, non-b hepatitis. between 1984 and 1986 harald zur hausen and lutz gissmann discovered hpv16 and hpv18, together these papillomaviridae viruses (hpv) are responsible for approximately 70% of human papillomavirus infections that cause cervical cancers. for the discovery that hpv cause human cancer the 2008 nobel prize was awarded. in 1987 the hepatitis c virus (hcv) was discovered by panning a cdna library made from diseased tissues for foreign antigens recognized by patient sera. this work was performed by michael houghton at chiron, a biotechnology company, and daniel w. bradley at the centers for disease control and prevention (cdc). hcv was subsequently shown to be a major contributor to hepatocellular carcinoma (liver cancer) worldwide. in 1994 patrick s. moore and yuan chang at columbia university), working together with ethel cesarman, isolated kaposi's sarcoma-associated herpesvirus (kshv or hhv8) using representational difference analysis. this search was prompted by work from valerie beral and colleagues who inferred from the epidemic of kaposi's sarcoma among patients with aids that this cancer must be caused by another infectious agent besides hiv, and that this was likely to be a second virus. subsequent studies revealed that kshv is the "ks agent" and is responsible for the epidemiologic patterns of ks and related cancers. in 2008 yuan chang and patrick s. moore developed a new method to identify cancer viruses based on computer subtraction of human sequences from a tumor transcriptome, called digital transcriptome subtraction (dts). dts was used to isolate dna fragments of merkel cell polyomavirus from a merkel cell carcinoma and it is now believed that this virus causes 70–80% of these cancers.