Viral oncogenesis describes how certain viruses contribute to cancer development. This field explores how viral infections alter cellular functions, leading to uncontrolled cell division and tumor formation. Understanding this relationship is a significant area in cancer research, providing insights into cancer causes and informing prevention and treatment strategies. It highlights that only a specific subset of viruses causes cancer, making them a focus for public health initiatives.
Mechanisms of Viral Oncogenesis
Viruses can initiate cancer through several distinct mechanisms that disrupt normal cell regulation. One common pathway involves the insertion of viral genetic material into the host cell’s DNA. This integration can interrupt tumor suppressor genes or activate proto-oncogenes, leading to uncontrolled proliferation. Viruses may also produce oncoproteins that interfere with cellular processes regulating cell growth, division, and programmed cell death. These viral oncoproteins can bind to and inactivate host tumor suppressor proteins like p53 and pRb, allowing damaged cells to continue dividing unchecked.
Another mechanism involves the induction of chronic inflammation within infected tissues. Persistent viral infections can cause long-term inflammatory responses, which generate reactive oxygen species and lead to DNA damage. This sustained inflammation also promotes cell proliferation as the body attempts to repair damaged tissue, increasing the likelihood of mutations accumulating over time. Some viruses can also suppress the host immune system, preventing the body from effectively identifying and eliminating infected or abnormal cells. This immune evasion allows virally altered cells to escape detection and proliferate, contributing to tumor growth.
Key Oncogenic Viruses and Associated Cancers
Several human viruses are recognized for their ability to cause cancer, collectively accounting for an estimated 15-20% of all human cancers worldwide. Human Papillomavirus (HPV) is an example, with persistent infections by high-risk types being the main cause of cervical cancer. HPV also causes most anal cancers, a significant portion of oropharyngeal (throat) cancers, and many cancers of the vulva, vagina, and penis. In 2019, HPV was estimated to cause 620,000 cancer cases in women and 70,000 in men globally.
Hepatitis B Virus (HBV) is a leading cause of hepatocellular carcinoma (HCC), a common type of liver cancer. Chronic HBV infection accounts for at least 50% of HCC cases globally, with individuals chronically infected from birth facing up to a 25% lifetime risk of developing liver cancer without intervention. Hepatitis C Virus (HCV) is also a major cause of HCC, contributing to liver inflammation, fibrosis, and cirrhosis, which can progress to cancer. Chronic HCV infection is also linked to non-Hodgkin lymphoma and possibly head and neck cancers.
Epstein-Barr Virus (EBV) is a widespread virus associated with several malignancies. It is linked to nasopharyngeal carcinoma (a type of throat cancer) and certain lymphomas, including Burkitt and Hodgkin lymphoma. EBV is also associated with some gastric cancers and has a suspected link to breast cancer. Human T-lymphotropic Virus Type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), an aggressive blood cancer. A small proportion, about 5%, of HTLV-1 infected individuals develop ATL, often decades after initial infection.
Kaposi’s Sarcoma-associated Herpesvirus (KSHV or HHV-8) is the causative agent of Kaposi sarcoma (KS), a cancer commonly seen in individuals with weakened immune systems, such as those with HIV/AIDS. KSHV also causes primary effusion lymphoma and HHV-8-associated multicentric Castleman disease, both aggressive lymphoproliferative disorders. Merkel Cell Polyomavirus (MCPyV) is responsible for the majority of Merkel cell carcinoma cases, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors are infected with MCPyV, which is believed to be a common, asymptomatic infection in older children and adults.
Preventing Viral-Driven Cancers
Preventing viral infections is an effective strategy to reduce the incidence of associated cancers. Vaccination is a preventive measure against specific oncogenic viruses. The HPV vaccine, for example, can prevent infection with high-risk HPV types, preventing over 90% of HPV-related cancers, including cervical, anal, and oropharyngeal cancers. Similarly, hepatitis B vaccines are effective in preventing chronic HBV infections, which significantly reduces the risk of liver cancer.
Beyond vaccination, screening programs play a role in early detection of pre-cancerous changes or early-stage cancers in at-risk populations. For instance, cervical cancer screening, using Pap tests and HPV DNA tests, can identify precancerous lesions before they develop into cancer, allowing for timely intervention. While there is no vaccine for Hepatitis C Virus, screening for HCV infection is recommended, especially for high-risk groups, as effective antiviral treatments can cure the infection and reduce liver cancer risk.
Safe practices also contribute to preventing the transmission of certain viruses. Avoiding exposure to infected blood through safe injection practices and screened blood transfusions helps prevent HCV transmission. For HTLV-1, avoiding needle sharing, practicing safe sex, and preventing mother-to-child transmission through breastfeeding can limit its spread. Antiviral therapies can also reduce viral load and lower cancer risk, as seen with direct-acting antivirals for HCV, which can cure over 95% of infections and significantly reduce the risk of liver disease progression and cancer mortality.