An oncovirus, also known as a tumor virus, is a virus that can cause cancer in humans or animals. A small, distinct group of these viruses is classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC). They achieve their cancer-causing effect by establishing a persistent infection, which allows them to interfere with the host cell’s genetic programming over time and alter cellular processes to promote malignancy. The study of oncoviruses has been instrumental in understanding the fundamental mechanisms of cancer development, particularly the control systems that regulate cell growth and division.
The Process of Viral Carcinogenesis
Oncoviruses promote cancer by disrupting the balance of cell growth and death through their own proteins, termed viral oncogenes. Many of these viruses, particularly DNA tumor viruses, encode proteins designed to interfere with two major tumor suppressor proteins: p53 and the retinoblastoma protein (pRb). These two cellular proteins are central regulators of the cell cycle, acting as checkpoints that stop a cell from growing and dividing if its DNA is damaged.
The pRb protein normally acts as a brake, binding to and inactivating a transcription factor called E2F, which is necessary for the cell to enter the S phase (DNA synthesis). Viral proteins, such as the E7 protein from Human Papillomavirus, bind to pRb and force it to release E2F prematurely, leading to uncontrolled cell division. Similarly, the p53 protein acts as the “guardian of the genome,” triggering cell cycle arrest or programmed cell death (apoptosis) in response to abnormal growth signals or DNA damage.
Viral oncoproteins, like the HPV E6 protein, target p53 for degradation by hijacking the cell’s protein disposal machinery. Inactivating both p53 and pRb ensures the host cell continues to divide despite having damaged DNA, promoting malignant transformation. For some viruses, such as Hepatitis B Virus (HBV) and Human Papillomavirus (HPV), the integration of viral genetic material into the host cell’s genome can directly disrupt cellular genes or lead to the persistent expression of cancer-promoting viral proteins. Other viruses, like Hepatitis C Virus (HCV), cause cancer indirectly by inducing chronic inflammation, which repeatedly damages the host cell’s DNA and promotes mutations.
Major Viruses That Cause Cancer
The majority of human cancers linked to viruses are caused by a small, well-defined group of seven oncoviruses. Each virus is linked to specific cancer types and is responsible for a wide range of malignancies globally.
Human Papillomavirus (HPV) is the most common viral cause of cancer, responsible for nearly all cases of cervical cancer, and a significant proportion of anal, vaginal, vulvar, penile, and oropharyngeal (throat) cancers. The high-risk types, particularly HPV-16 and HPV-18, are the primary culprits.
Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are the leading causes of liver cancer (hepatocellular carcinoma or HCC), together accounting for three-quarters of these cases. These viruses cause chronic infection in the liver, leading to inflammation, fibrosis, and ultimately, cancer.
Epstein-Barr Virus (EBV), a common herpesvirus, is associated with several cancers, including Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. EBV infects B-cells and epithelial cells, and its oncogenic potential is tied to viral proteins that promote cell survival and growth.
Kaposi’s Sarcoma-associated Herpesvirus (KSHV), also called Human Herpesvirus 8 (HHV-8), causes nearly all cases of Kaposi’s sarcoma. This is a cancer of the blood and lymph vessels most often seen in individuals with compromised immune systems, such as those with advanced HIV infection. KSHV is also linked to two rare B-cell lymphomas.
Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that infects T-lymphocytes and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a rare but aggressive blood cancer. This virus is prevalent in certain regions, including parts of Japan, the Caribbean, and Central Africa.
Merkel cell polyomavirus (MCV) is a recently discovered oncovirus that is the primary cause of about 80% of Merkel cell carcinoma, a rare but aggressive form of skin cancer. MCV is commonly found on the skin of healthy people, but it can trigger cancer when its DNA integrates into the host cell’s genome.
Strategies for Preventing Viral Cancers
Prevention efforts for viral cancers focus on vaccination, screening, and reducing transmission risks. Vaccines are the most effective strategy for primary prevention, as they block the infection before the carcinogenic process can initiate.
Vaccination against HPV has demonstrated high efficacy in preventing persistent infection and the development of pre-cancers and cancers. The HPV vaccine is recommended for preteens around ages 11 to 12, or as early as age 9, with the goal of administering it before any exposure to the virus. This vaccine can prevent more than 90% of the cancers caused by HPV, including cervical, anal, and oropharyngeal cancers.
The Hepatitis B vaccine is a successful tool for preventing chronic HBV infection and the resulting liver cancer. Global efforts focus on vaccinating all newborns, often within 24 hours of birth, because infants infected with the virus are the most likely to develop chronic infection and later liver cancer. For HCV, while no vaccine exists, antiviral treatments can cure the infection, eliminating the underlying cause of the cancer risk.
Screening programs are a secondary preventative measure, especially for HPV-related cancers. Cervical cancer screening, using the Pap test and the HPV test, can detect precancerous cell changes or the presence of the high-risk virus before cancer develops. Reducing transmission risk through safe sex practices and avoiding shared needles can also lower the likelihood of acquiring these oncogenic viruses.
Scope of Virus-Associated Malignancies
Viruses contribute to a substantial portion of the global cancer burden, with estimates suggesting that infections cause approximately 10% to 20% of all human cancer cases worldwide. This means more than a million cancer cases each year are attributable to a viral infection.
The burden of these virus-linked cancers is not distributed equally across the globe. Developing regions, particularly in sub-Saharan Africa and parts of Asia, bear a disproportionately high percentage of cases, where viral infections can account for more than a quarter of all cancers. This disparity is often due to limited access to public health interventions, such as vaccination programs and screening.
Cervical cancer, which is almost entirely caused by HPV, is a leading cause of cancer death among women in many low-income countries. The global impact of these viruses on specific cancer types is profound; nearly 100% of cervical cancers and Kaposi’s sarcomas are linked to a viral cause. This scale emphasizes that many cancers are preventable through targeted strategies against these infectious agents.