19.2 Major human oncogenic viruses and associated cancers
4 min read•august 1, 2024
Viruses can cause cancer by hijacking our cells. Some major culprits include HPV, EBV, HBV, and HTLV-1. These sneaky invaders mess with our DNA and cell signaling, leading to uncontrolled growth.
Each virus has its favorite targets. HPV goes for cervical cells, EBV attacks lymphocytes, HBV hits the liver, and HTLV-1 infects T-cells. Understanding how they spread and who's at risk helps us fight back against these cancer-causing troublemakers.
Oncogenic Viruses
Major Human Oncogenic Viruses
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- consists of double-stranded DNA belonging to family
- Over 200 types identified
- Approximately 40 types can infect the genital tract
- comprises double-stranded DNA virus of family
- Also known as human herpesvirus 4
- Infects B lymphocytes and epithelial cells
- contains partially double-stranded DNA of family
- Primarily infects hepatocytes in the liver
- encompasses single-stranded RNA retrovirus
- Mainly infects CD4+ T lymphocytes
Additional Oncogenic Viruses and Mechanisms
- Other notable oncogenic viruses include hepatitis C virus (HCV), Kaposi's sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV)
- Viruses induce cellular transformation through various mechanisms
- Expression of (E6 and E7 in HPV)
- Integration into the host genome (HBV)
- Manipulation of cellular signaling pathways ( by HTLV-1)
Cancer Types Associated with Viruses
HPV-Associated Cancers
- serves as primary cancer associated with HPV
- High-risk HPV types 16 and 18 cause approximately 70% of cervical cancer cases worldwide
- Other HPV-related cancers include:
- (anal, vulvar, vaginal, penile)
EBV-Associated Cancers
- Various lymphomas linked to EBV:
- strongly associated with EBV
- Subset of , particularly in Asia, linked to EBV infection
HBV and HCV-Associated Cancers
- Hepatocellular carcinoma (HCC) represents major cancer caused by HBV
- Chronic HBV infection significantly increases HCC risk
- Cirrhosis often precedes HCC development
- HCV also causes hepatocellular carcinoma
- Associated with some B-cell lymphomas
HTLV-1-Associated Cancers
- caused by HTLV-1
- Rare and aggressive form of blood cancer
- HTLV-1 also associated with neurological condition called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
Epidemiology of Virus-Associated Cancers
Global Burden and Distribution
- Virus-associated cancers account for 15-20% of all human cancers worldwide
- Significant variations in prevalence across geographic regions
- HPV-associated cancers have high global burden
- Cervical cancer ranks as fourth most common cancer in women worldwide
- Particularly affects low- and middle-income countries
- EBV infection ubiquitous with over 90% of adults worldwide seropositive
- EBV-associated cancers show distinct geographic patterns
- Burkitt's lymphoma endemic in equatorial Africa
- Nasopharyngeal carcinoma highly incident in Southern China and Southeast Asia
Prevalence of Specific Virus-Associated Cancers
- Chronic HBV infection affects approximately 257 million people globally
- Highest prevalence in Western Pacific and African regions
- HBV-related hepatocellular carcinoma accounts for significant proportion of liver cancer cases
- HTLV-1 infection endemic in certain geographic areas
- Southwestern Japan, Caribbean, parts of South America and Africa
- Lifetime risk of developing ATLL in HTLV-1 carriers estimated at 2-7%
Factors Influencing Global Burden
- coverage impacts virus-associated cancer prevalence (HPV vaccine)
- Screening programs affect early detection and prevention (cervical cancer screening)
- Access to healthcare leads to disparities between developed and developing countries
- Environmental and lifestyle factors contribute to regional variations in cancer incidence
Risk Factors for Oncogenic Viruses
Transmission Routes
- Sexual transmission serves as primary route for HPV
- Risk factors include multiple sexual partners, early sexual debut, unprotected sexual activity
- Vertical transmission from mother to child during childbirth possible but less common
- EBV primarily transmitted through saliva ("kissing disease")
- Can also spread through blood and organ transplantation
- HBV transmitted through blood, bodily fluids, and vertical transmission
- HTLV-1 spread through breast milk, sexual contact, blood transfusions, and sharing contaminated needles
- Prolonged breastfeeding (>6 months) significantly increases risk of mother-to-child transmission
Co-factors and Environmental Risks
- Co-infection with HIV increases risk of developing virus-associated cancers due to immunosuppression
- Behavioral and environmental factors act as co-factors in virus-induced carcinogenesis
- Alcohol consumption
- Smoking
- Exposure to certain chemicals (aflatoxin for HBV-related HCC)
- Genetic susceptibility influences development of virus-associated cancers (EBV-related nasopharyngeal carcinoma)
- Immunosuppression increases risk of virus-associated cancers (post-transplant lymphoproliferative disorders)
Key Terms to Review (28)
Adult T-cell leukemia/lymphoma (ATLL): Adult T-cell leukemia/lymphoma (ATLL) is a type of cancer that affects the T-cells, specifically the CD4+ T-lymphocytes, and is associated with infection by the Human T-lymphotropic virus type I (HTLV-I). This malignancy often manifests in adults, leading to a variety of symptoms such as skin lesions, lymphadenopathy, and immune dysfunction. The connection to HTLV-I highlights the role of oncogenic viruses in the development of certain cancers, illustrating how viral infections can have long-term impacts on human health.
Anogenital cancers: Anogenital cancers refer to malignancies that occur in the anal and genital regions, including the anus, vulva, vagina, and penis. These cancers are often associated with specific risk factors, including infection by certain oncogenic viruses, which can contribute to their development.
Burkitt's lymphoma: Burkitt's lymphoma is a type of non-Hodgkin lymphoma characterized by the rapid growth of tumors, primarily affecting the B cells of the immune system. It is often associated with infections from the Epstein-Barr virus (EBV), which belongs to the herpesvirus family, and is known for its strong link to immunosuppression and specific geographic locations, notably in Africa. Understanding this condition involves exploring its viral associations and its classification as an oncogenic disease.
Case-control studies: Case-control studies are a type of observational study designed to identify and compare the exposure to a certain risk factor or characteristic among individuals with a specific outcome (cases) and those without that outcome (controls). These studies are particularly useful in investigating rare diseases or conditions, allowing researchers to gather insights into potential causes and contributing factors.
Cervical cancer: Cervical cancer is a type of cancer that occurs in the cells of the cervix, often linked to persistent infection with high-risk types of human papillomavirus (HPV). This cancer can develop over time from precancerous changes in the cervical cells, which are typically caused by HPV infection, and is a significant public health concern due to its association with specific oncogenic viruses.
Cohort studies: Cohort studies are observational research methods where a group of individuals with shared characteristics, known as a cohort, is followed over time to observe outcomes, particularly the development of diseases or health conditions. This method is crucial in understanding the risk factors and long-term effects of exposures, making it vital for studying disease outbreaks and identifying links between viruses and cancers.
Diffuse large B-cell lymphoma: Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma characterized by the rapid growth of large B-cells, which are a form of white blood cell. DLBCL is considered the most common type of aggressive lymphoma and can arise in lymph nodes or outside the lymphatic system, often leading to serious health implications. Understanding the connection between DLBCL and human oncogenic viruses helps in recognizing its etiology and potential therapeutic targets.
Epstein-Barr Virus (EBV): Epstein-Barr Virus (EBV) is a member of the herpesvirus family and is known for causing infectious mononucleosis and has been implicated in various malignancies. This virus is significant in the study of human oncogenic viruses, as it is associated with several types of cancer, including Hodgkin's lymphoma and Burkitt's lymphoma. Understanding EBV is essential for developing effective prevention and treatment strategies for virus-associated cancers.
Gastric carcinomas: Gastric carcinomas are malignant tumors that originate in the stomach lining, representing a major type of gastric cancer. These tumors often arise from the epithelial cells and are linked to various risk factors including infection with certain viruses, particularly Helicobacter pylori, and environmental influences. Understanding gastric carcinomas is crucial as they are among the leading causes of cancer-related deaths worldwide.
Hepadnaviridae: Hepadnaviridae is a family of viruses that includes those known to cause liver infections in humans and other animals, characterized by their partially double-stranded DNA genome. This virus family is significant for its role in human health, particularly in relation to chronic liver diseases, including hepatitis and liver cancer.
Hepatitis b virus (hbv): Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that primarily infects the liver, leading to inflammation and potentially serious liver conditions. This virus is a major human oncogenic virus, recognized for its association with chronic liver disease and hepatocellular carcinoma, making it a significant concern in the context of cancer prevention and treatment strategies.
Herpesviridae: Herpesviridae is a large family of viruses known as herpesviruses that can infect humans and animals, characterized by their ability to establish lifelong latency in host cells. This family is significant for its diverse members, which include various human pathogens that can cause diseases ranging from mild to severe, and it plays an important role in understanding viral behavior, transmission, and pathogenesis.
Hodgkin's Lymphoma: Hodgkin's lymphoma is a type of cancer that originates in the lymphatic system, characterized by the presence of Reed-Sternberg cells. It is classified as a malignant lymphoma, which means it can spread throughout the body and affect other organs, often leading to significant health complications. The disease is associated with certain viral infections, making its study particularly relevant when discussing oncogenic viruses and their roles in cancer development.
Human papillomavirus (HPV): Human papillomavirus (HPV) is a group of over 200 related viruses, some of which are known to cause warts and others that can lead to various cancers, particularly cervical cancer. Certain high-risk types of HPV are considered major oncogenic viruses, meaning they have a strong association with the development of cancers, and understanding their role in cancer biology is crucial for prevention strategies.
Human t-cell leukemia virus type 1 (htlv-1): Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that primarily infects T-cells and is known for its association with certain types of cancers, particularly adult T-cell leukemia/lymphoma (ATLL). This virus is unique among human viruses due to its ability to integrate into the host genome and persist in infected individuals, leading to chronic infections that can take years to develop into malignancy.
Immune evasion: Immune evasion refers to the various strategies employed by viruses to avoid detection and destruction by the host immune system. These tactics can significantly influence a virus's ability to spread, establish infection, and cause disease, highlighting the intricate arms race between viruses and their hosts.
Nasopharyngeal carcinoma: Nasopharyngeal carcinoma is a type of cancer that arises in the nasopharynx, the area located behind the nose and above the back of the throat. It is strongly associated with certain viral infections, particularly Epstein-Barr virus (EBV), which is part of the herpesvirus family. This cancer is notable for its geographical distribution, being more prevalent in certain parts of Asia and North Africa, highlighting the role of environmental and genetic factors in its development.
Nf-κb activation: nf-κb activation refers to the process by which a family of transcription factors, known as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), is activated in response to various stimuli, including viral infections. This activation plays a crucial role in regulating immune responses, cell survival, and inflammation, and is significantly implicated in the development of various cancers associated with oncogenic viruses.
Oncogene activation: Oncogene activation refers to the process by which normal genes, known as proto-oncogenes, are converted into oncogenes that promote cancer development. This transformation often occurs through genetic mutations, chromosomal rearrangements, or viral insertions that lead to uncontrolled cell proliferation. Understanding oncogene activation is essential for grasping how certain viruses induce cancer and the specific types of cancers associated with various oncogenic viruses.
Oropharyngeal cancers: Oropharyngeal cancers refer to malignancies that occur in the oropharynx, which is the middle part of the throat located behind the mouth, including areas such as the tonsils and the base of the tongue. These cancers have been increasingly associated with certain oncogenic viruses, particularly human papillomavirus (HPV), highlighting the critical relationship between viral infections and cancer development.
Papillomaviridae: Papillomaviridae is a family of small, double-stranded DNA viruses known for their ability to cause warts and various cancers in humans. This family includes more than 200 different types, with some strains being particularly associated with oncogenic properties, leading to the development of certain cancers, most notably cervical cancer.
PCR Testing: PCR testing, or Polymerase Chain Reaction testing, is a molecular biology technique used to amplify small segments of DNA, making it easier to analyze and detect the presence of specific genetic material. This method has become a cornerstone in diagnosing various viral infections, including herpesviruses and other clinically significant DNA viruses, as well as identifying oncogenic viruses associated with certain cancers.
Screening protocols: Screening protocols are systematic procedures designed to identify individuals at risk of specific diseases or conditions, including cancers associated with oncogenic viruses. These protocols utilize various tests and assessments to detect early signs of disease, enabling timely intervention and management. In the context of major human oncogenic viruses, screening protocols are crucial for monitoring populations at risk for developing virus-related cancers, such as cervical cancer linked to Human Papillomavirus (HPV) or liver cancer associated with Hepatitis B and C viruses.
Serological Assays: Serological assays are laboratory techniques used to detect and measure the presence of antibodies, antigens, or other immune components in a sample, often blood serum. These assays are crucial for diagnosing infections, determining immune status, and studying virus-host interactions, which is essential for understanding disease symptoms, transmission dynamics, and the role of specific viruses in cancer development.
Tumor microenvironment: The tumor microenvironment refers to the surrounding cellular environment where a tumor develops, consisting of various cell types, extracellular matrix components, blood vessels, and signaling molecules. This environment plays a crucial role in influencing tumor behavior, growth, and response to therapies, particularly in the context of cancers associated with oncogenic viruses.
Vaccination: Vaccination is a medical procedure that involves administering a vaccine to stimulate the body's immune response against specific pathogens, primarily viruses and bacteria. This process not only helps protect individuals from infections but also plays a vital role in controlling the spread of infectious diseases within populations.
Viral integration: Viral integration refers to the process by which a virus incorporates its genetic material into the DNA of a host cell. This integration can lead to permanent changes in the host genome, which can disrupt normal cellular functions and contribute to oncogenesis, or the formation of tumors. Understanding viral integration is crucial for comprehending how certain viruses are capable of inducing cancer in infected individuals.
Viral oncoproteins: Viral oncoproteins are proteins produced by oncogenic viruses that have the ability to induce cellular transformation, leading to uncontrolled cell growth and cancer. These proteins can disrupt normal cellular processes by interfering with tumor suppressor genes and promoting cell cycle progression. The interaction of viral oncoproteins with host cellular mechanisms plays a crucial role in the development of virus-induced malignancies.