When we think about cancer, we often associate it with genetic mutations, environmental factors, or lifestyle choices such as smoking. However, approximately 15-20% of cancers are caused by viruses, especially sexually transmitted viruses such as human papillomavirus (HPV), hepatitis B (HBV) and C (HCV)1. These viruses, termed oncoviruses, generally have several features in common: they are mostly DNA viruses, they mainly encode growth-stimulating proteins, and they establish persistent, long-term infection in the host, causing cancer 15-40 years after the initial infection2. Infection with oncoviruses may cause cancer directly by dysregulating tumor suppressor genes and other oncogenes in the host, or indirectly, by way of chronic inflammation or immune suppression. In this blog, we will provide a comprehensive overview of the seven known oncoviruses, HPV, HBV, HVC, Epstein-Barr virus (EBV), human T-lymphotropic virus 1 (HTLV-1), human herpesvirus 8 (HHV-8) and Merkel cell polyomavirus (MCPyV), as well as HIV, which is not technically an oncovirus but infection with HIV renders a patient vulnerable to developing malignancies, especially those transmitted by oncogenic viruses.
Human papillomaviruses (HPVs)
Human papillomaviruses (HPVs) are a group of more than 150 related viruses that commonly cause warts. More than 40 types of HPV are sexually transmitted and according to the World Health Organization (WHO), HPV is the most common global sexually transmitted infection (STI) with up to 80% of sexually active people infected with one or more HPV virus type at some point in their lives. Approximately a dozen HPV types are known to cause cancer, and certain high-risk strains of HPV, particularly HPV types 16 and 18, are linked cervical cancer, which is the second most common cancer among women worldwide.
HPV infection can also lead to anal cancer (90% are caused by HPV), oropharyngeal cancer (70% are caused by HPV), penile cancer (63% are caused by HPV), vaginal cancer (75% are caused by HPV), and vulvar cancer (69% are caused by HPV)3.
However, cervical cancer is currently the only HPV-causing cancer with FDA-approved screening tests.
Hepatitis B Virus (HBV) & hepatitis C Virus (HCV)
Viral hepatitis, a type of liver infection, is caused by hepatitis viruses, in particular hepatitis B (HBV) and hepatitis C (HCV). Globally, viral hepatitis is responsible for 80% of liver cancers and untreated chronic HBV or HCV infections represent the fastest-increasing cause of cancer death and the second fastest-increasing incidence of all cancers 4.
HBV and HCV are spread from person to person through sharing needles (such as during injection drug use), unprotected sex, or childbirth. The viruses can integrate their genetic material into the host cell’s DNA, disrupt cellular regulatory mechanisms, and promote uncontrolled cell growth, thereby contributing to the development of liver cancer. While not all cases of viral hepatitis lead to liver cancer, chronic infection with HBV or HCV significantly increases the risk of developing hepatocellular carcinoma over time.
Epstein-Barr virus (EBV)
Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a type of herpes virus best known for causing infectious mononucleosis, often called “mono” or the “kissing disease.” In addition to kissing, EBV can be passed from person to person by coughing, sneezing, or by sharing drinking or eating utensils. More than 90% of the world’s population has been infected with EBV by their teen years5.
As with other herpes virus infections, EBV infection is life-long and stays latent in memory B cells. Infection with EBV increases the risk of several cancers, including Burkitt lymphoma, some types of Hodgkin’s and non-Hodgkin’s lymphoma, and stomach cancer. Overall, it’s estimated that EBV infection contributes to about 1.5% of cancers worldwide, with EBV-related cancers being more common in Africa and parts of Southeast Asia6.
Human herpes virus 8 (HHV-8)
HHV-8, also known as Kaposi sarcoma–associated herpes virus (KSHV), belongs to the same family as EBV and causes Kaposi sarcoma (KS), a cancerous tumor of the connective tissue. KSHV is transmitted mainly through saliva, however, it can also be spread through sexual contact, blood transfusion, or transplants.
The seroprevalence of HHV-8 varies worldwide and is estimated to be 1% to 5% in the U.S. general population, 10% to 20% in certain Mediterranean countries and 30% to 80% in parts of sub-Saharan Africa. HIV-infection is an important risk factor for developing KS with almost 30% of AIDS patients infected with KS prior to the advent of effective antiretroviral therapy7.
Human T-lymphotrophic virus-1 (HTLV-1)
HTLV-1 is a complex retrovirus that belongs to the primate T-lymphotropic virus (PTLV) family. It is a sexually transmitted disease endemic to Japan, Melanesia, Iran, Central and West Africa, the Caribbean, Australia, and the Middle East. Approximately 10 million people are infected with HTLV-1 around the world, but most of them remain asymptomatic. Only a small proportion (2%–5%) of HTLV-1-infected humans progress to adult T-cell leukemia/lymphoma (ATL), a very aggressive form of leukemia8.
Merkel cell polyomavirus (MCPyV)
Merkel cell polyomavirus (MCPyV) is a virus associated with Merkel cell carcinoma (MCC), a rare but aggressive type of skin cancer that typically occurs in sun-exposed areas of the skin, such as the head and neck. The virus is found on the skin and mucosal surfaces and is thought to be a part of the normal human skin microbiome9.
MCPyV is transmitted through close contact with infected individuals and many people carry the virus without developing cancer. The development of MCC usually involves additional factors such as a weakened immune system or excessive exposure to ultraviolet (UV) radiation. Immunocompromised individuals, such as those with HIV/AIDS or undergoing organ transplantation and receiving immunosuppressive therapy, are at higher risk of developing MCC associated with MCPyV infection.
Human immunodeficiency virus (HIV)
HIV, the virus that causes acquired immune deficiency syndrome (AIDS), is not an oncovirus that can cause cancer directly, but an infection that increases a person’s risk of getting several types of cancer, especially those caused by oncoviruses. HIV infects and destroys white blood cells known as helper T-cells, which weakens a body’s immune system causing it to be more susceptible to the development of cancer, including Hodgkin disease, Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer, and cancer of the skin, anus, lung, and liver10.
The Vital Role of Testing in Detecting Asymptomatic Oncoviruses and Preventing Cancer
Understanding the role of viruses in cancer development is critical for developing preventive measures and targeted treatments. However, many oncoviruses are asymptotic, making them challenging to detect and diagnose, and individuals unaware that they are infected inadvertently transmit the infection to others. Routine screening and early detection can help identify viral infections before they progress to cancer or other serious complications.
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References:
1. Bouza E., et al. (2021). Overview of virus and cancer relationships. Position Paper. Rev Esp Quimioter. 34(6):525-555. doi: 10.37201/req/058.2021.
2. Kainat A. and Sudhakar J. (2023). Oncoviruses: How do they hijack their host and current treatment regimes, Biochimica et Biophysica Acta (BBA) – Reviews on Cancer. 1878(5). doi: org/10.1016/j.bbcan.2023.188960.
3. National Cancer Institute. HPV and Cancer. U.S. Department of Health and Human Services.
5. Dunmire S.K., et al. (2015). Infectious Mononucleosis. Curr Top Microbiol Immunol. 390(Pt 1):211-40. doi: 10.1007/978-3-319-22822-8_9.
6. Shechter O., et al. (2022). Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments. Int J Mol Sci. 23(22):14389. doi: 10.3390/ijms232214389.
7. Clinical Info HIV Gov. Federally Approved Clinical Practice Guidelines for HIV/AIDS
9. Yang J.F. and You J. (2022) Merkel cell polyomavirus and associated Merkel cell carcinoma. Tumour Virus Res. 200232. doi 10.1016/j.tvr.2021.200232.
10. Omar A., et al. (2024) Cancer and HIV: The Molecular Mechanisms of the Deadly Duo. Cancers (Basel). 16(3):546. doi: 10.3390/cancers16030546.