Oncogenic viruses
Oncogenic viruses, also known as oncoviruses, are viruses that can transform normal cells into cancer cells, leading to various malignancies in humans and other animals. These viruses can possess either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) genomes and are associated with a notable percentage of cancer diagnoses, especially in certain regions, such as sub-Saharan Africa, where viral infections account for a significant portion of cases. Key oncogenic viruses include the Epstein-Barr virus (EBV), human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), among others. They are typically transmitted through sexual contact, blood exchange, or bodily fluids, placing individuals who are immunosuppressed or engage in risky behaviors at higher risk.
The types of cancers linked to these viruses include, but are not limited to, cervical cancer, liver cancer, and several lymphomas. Historical research into oncogenic viruses dates back over a century, with significant breakthroughs occurring in the identification of human oncoviruses in the 1960s and 1980s. Notably, the development of an HPV vaccine has greatly reduced cervical cancer rates, showcasing the progress made in this field. Current research continues to explore treatments and prevention strategies for infections associated with these viruses, highlighting their ongoing impact on public health.
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Oncogenic viruses
ALSO KNOWN AS: Oncoviruses
RELATED CANCERS: Cancers of the cervix, skin, head, neck, uterus, penis, nasopharynx, and liver; adenocarcinoma; Kaposi sarcoma-associated herpes virus; Burkitt lymphoma; non-Hodgkin's lymphoma; adult T-cell leukemia; B-cell lymphomas; T-cell lymphomas; Hepatocellular carcinoma; nasopharyngeal carcinoma; EBV-associated gastric cancer; leiomyosarcoma; head and neck squamous cell carcinoma; epidermodysplasia verruciformis
DEFINITION: An oncogenic virus is a virus that infects normal cells, alters the cells’ properties, and transforms them into cancer cells. Oncogenic viruses can cause cancer in a variety of animals, including humans. These viruses can have a deoxyribonucleic acid (DNA) genome or a ribonucleic acid (RNA) genome.
Exposure routes: Sexual, blood-to-blood contact; exchange of bodily fluids
Where found: Ubiquitous
At risk: Individuals in close contact with others infected with oncoviruses, have unprotected sex, use intravenous drugs, or are immunosuppressed are at increased risk. Overall, between 12 and 20 percent of cancer diagnoses are caused by viral infections, and in parts of sub-Saharan Africa, closer to 45 percent of cases are attributed to viruses.
Etiology and symptoms of associated cancers: Many viruses can cause tumors in animals, but seven viruses cause around twenty malignancies in humans. Etiology depends on whether the genetic material is DNA or RNA. DNA viruses include the Epstein-Barr virus (EBV), human papillomavirus (HPV), human herpesvirus-8 (HHV-8), hepatitis B virus (HBV), and RNA viruses include the human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV). The EBV and HHV-4 have been strongly linked to nasopharyngeal cancer and certain forms of Burkitt lymphoma endemic to Central Africa. EBV is also a cause of some cases of Hodgkin's disease. Human herpesvirus-8 (HHV-8) is linked to Kaposi sarcoma-associated herpes virus (KSHV). Around 90 percent of hepatocellular carcinoma (HCC) cases are caused by HBV and HCV.
Adenoviruses are suspected of causing cancer of glandular epithelial tissues, a disease known as adenocarcinoma. The human papillomavirus (HPV) can cause various conditions, from warts to cancers, such as carcinomas of the cervix, uterus, and penis. Some cancers of the lung, larynx, and esophagus may be related to HPV. Although there are more than one hundred recognized types of HPV, only a few are known to cause cancer. First described in 2008, Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas.
Upon entering a cell, viral DNA may integrate into the host genome and express its viral genes, the oncogenes, which cause tumors. Sometimes, the virus integrates next to a cellular gene and causes cancer by inducing an overexpression of that cellular gene.
The RNA viruses associated with human cancers are human T-cell leukemia viruses 1 and 2 (HTLV-1 and HTLV-2), which cause adult T-cell leukemia and hairy cell leukemia, respectively; the hepatitis C virus (HCV); and the human immunodeficiency virus (HIV), which is suspected of causing lymphomas.
When an RNA tumor virus enters the cell, a DNA copy of its RNA is made in a process known as reverse transcription. The DNA copy may integrate into the host genome and express the viral gene that causes cancer. Alternatively, the integrated DNA can cause cancer by inducing the overexpression of a cellular gene.
History: In 1910, Peyton Rous discovered that viruses caused sarcomas in chickens. However, it was not until 1964 that Anthony Epstein and Yvonne Barr became the first researchers to identify a human oncovirus, the Epstein-Barr virus, in their study of Burkitt lymphoma cells. By the 1970s, it was clear that certain viruses caused cancer in humans. In 1980, the first human retrovirus, human T-lymphotropic virus 1 (HTLV-1), was identified. In the mid-1980s, German virologist Harald Zur Hausen discovered the role of HPV in the development of cervical cancers. Zur Hausen's discovery enabled the development of an HPV vaccine, which was introduced in 2006 and greatly curtailed the rates of HPV transmission. Zur Hausen earned the Nobel Prize in Physiology or Medicine in 2008 for his discovery. In 2008, Patrick S. Moore and Yuan Chang isolated the Merkel cell polyomavirus from Merkel cell carcinoma cells.
Research is ongoing to prevent and control oncovirus infections and virus-related cancers. MiRNAs and anti-miRNA oligonucleotides (AMOs) such as miR-BART9, BART10-3p, and miR-BART20-5p have been proposed as treatments.
Bibliography
Brenner, Malcolm K., and Mien-Chie Hung, eds. Cancer Gene Therapy by Viral and Non-Viral Vectors. Wiley, 2014.
Kandeel, M. "Oncogenic Viruses-Encoded microRNAs and Their Role in the Progression of Cancer: Emerging Targets for Antiviral and Anticancer Therapies." Pharmaceuticals, vol. 16, no. 485, 2023. doi.org/10.3390/ph16040485.
MacLennan, Signe A., and Marco A. Marra. “Oncogenic Viruses and the Epigenome: How Viruses Hijack Epigenetic Mechanisms to Drive Cancer.” International Journal of Molecular Sciences, vol. 24, no. 11, 31 May. 2023, doi:10.3390/ijms24119543.
Pelengaris, Stella, and Michael Khan, eds. The Molecular Biology of Cancer. 2nd ed., Blackwell, 2013.
Robertson, Erle S., ed. Cancer Associated Viruses. Springer, 2012.
Wu, T.-C., Mei-Hwei Chang, and Kuan-Teh Jeang. Viruses and Human Cancer: From Basic Science to Clinical Prevention. 2nd ed., Springer, 2021.