Viral cancer refers to malignancies that are caused by or significantly linked to certain viral infections. A substantial portion of human cancers have a viral origin. Globally, virus infections are estimated to be the cause of over 1.4 million cancer cases annually, representing approximately 10% of the worldwide cancer burden. The recognition of specific human viruses as direct or indirect causes of cancer represents a major achievement in cancer research and intervention.
How Viruses Drive Cancer Development
Viruses can initiate cancer development through several mechanisms, often by manipulating the host cell’s machinery. One way is through integration, where viruses insert their genetic material, either DNA or RNA, directly into the host cell’s DNA. This insertion can disrupt normal gene function, potentially activating genes that promote cell growth (oncogenes) or inactivating genes that suppress tumor formation (tumor suppressor genes).
Some viruses produce proteins that interfere with the cell’s normal growth and division controls, leading to cell cycle dysregulation. These viral “oncoproteins” can activate cellular signaling pathways and alter gene expression, pushing the cell towards uncontrolled multiplication.
Chronic inflammation is another pathway through which viruses can contribute to cancer. Persistent viral infections can lead to long-term inflammation, which damages cells and promotes genetic mutations. This ongoing cellular stress can create an environment conducive to malignant transformation.
Viruses can also weaken the body’s immune system, a process known as immune suppression or evasion. By downregulating molecules that help the immune system detect infected cells, viruses allow abnormal cells to grow unchecked. This reduced immune surveillance enables the uncontrolled proliferation of transformed cells.
Common Viruses Linked to Cancer
Several common viruses have been identified as contributors to human cancers.
Human Papillomavirus (HPV)
HPV is a well-known example, with certain high-risk types, such as HPV 16 and 18, being responsible for a large majority of HPV-related cancers. HPV can lead to cancers of the cervix, anus, vulva, vagina, penis, and oropharynx (throat). While HPV infections are common, only persistent infections with high-risk types typically lead to cancer over many years.
Hepatitis B and C Viruses (HBV and HCV)
HBV and HCV are major causes of liver cancer, also known as hepatocellular carcinoma (HCC). Chronic infection with either HBV or HCV can lead to liver damage, inflammation, and scarring (cirrhosis), which significantly increases the risk of HCC. In some regions, these viruses are linked to over 80% of primary liver cancers.
Epstein-Barr Virus (EBV)
EBV is a common herpesvirus that infects over 90% of adults worldwide, often without causing symptoms. However, EBV has been linked to several cancers, including nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and certain stomach cancers. While EBV is widespread, EBV-associated cancers are relatively rare, suggesting that additional factors are necessary for cancer development.
Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)
KSHV, also known as Human Herpesvirus 8 (HHV-8), is the cause of Kaposi’s sarcoma. This cancer commonly affects the skin and internal organs and is more prevalent in individuals with weakened immune systems, such as those with HIV. KSHV is also linked to primary effusion lymphoma and a form of multicentric Castleman disease.
Merkel Cell Polyomavirus (MCV)
MCV was identified in 2008 and is associated with approximately 80% of Merkel cell carcinomas, a rare but aggressive form of skin cancer. This virus is widespread in the general population, with initial exposure often occurring in early childhood. The virus’s T antigen oncogene is expressed in tumor cells and is necessary for the growth of MCV-positive tumors.
Human T-cell Lymphotropic Virus Type 1 (HTLV-1)
HTLV-1 is a retrovirus that can cause adult T-cell leukemia/lymphoma (ATL), an aggressive blood cancer. While most individuals infected with HTLV-1 remain asymptomatic for life, about 5% may develop ATL, typically decades after initial infection. HTLV-1 is primarily transmitted through breastfeeding, sexual contact, and sharing needles.
Strategies to Prevent Viral Cancers
Preventing viral cancers often involves targeting the initial viral infection through public health strategies.
Vaccination
Vaccination is a highly effective prevention method. Vaccines are available for HPV and HBV, two viruses responsible for a significant global cancer burden. The HPV vaccine protects against the high-risk types of HPV that cause most cervical, anal, and other HPV-related cancers. Routine HPV vaccination is recommended for preteens, typically at ages 11 or 12, before potential exposure to the virus.
The Hepatitis B vaccine is also an effective method for preventing liver cancer by preventing HBV infection. It is recommended for all infants at birth and for individuals at higher risk of exposure. Increasing vaccination rates for both HPV and HBV can reduce the incidence of these preventable cancers.
Safe Practices
Beyond vaccination, safe practices reduce the transmission risks of certain cancer-linked viruses. For example, avoiding the sharing of needles or syringes prevents the spread of HBV and HCV. Practicing safe sex, including consistent condom use, can also reduce the transmission of sexually transmitted viruses like HPV, HBV, HCV, and HTLV-1. Screening blood products also helps prevent transmission through transfusions.
Early Detection and Screening
Early detection and screening programs are important for preventing the progression of viral infections to cancer. For instance, regular Pap tests for women can detect precancerous changes in cervical cells caused by HPV infection, allowing for early intervention before cancer develops. While screening exists for some viral-related cancers like cervical cancer, routine screening tests are not available for all types of HPV-related cancers.
Addressing Viral-Related Cancers
The viral link in certain cancers provides valuable context that can influence diagnosis and treatment approaches.
Diagnosis
Diagnosis often involves testing for the presence of the specific virus, which can aid in confirming the cause or assessing an individual’s risk. For example, HPV testing is increasingly used in cervical cancer screening to identify high-risk infections. Similarly, serological tests for HBV and HCV can confirm chronic infections, which are strong indicators for liver cancer risk.
Treatment
While the primary treatment for these cancers typically involves standard oncological therapies such as surgery, chemotherapy, and radiation, understanding the viral origin can sometimes guide decisions. For instance, in liver cancer caused by HBV or HCV, antiviral therapy may be administered alongside cancer treatments to manage the underlying viral infection. This integrated approach aims to control both the cancer and the viral driver.
Monitoring
The presence of the virus can also influence monitoring for recurrence or response to therapy. For example, in nasopharyngeal carcinoma linked to Epstein-Barr virus, measuring plasma EBV DNA levels can be a tool in managing the disease. The viral connection offers additional insights that can optimize patient care.