infection risk - carcinogenesis and cancer prevention

describe the general mechanisms of carcinogenesis induced by viral infections

• chronic inflammatory response to persistent viral infection - inflammation drives reactive oxygen species generation which causes DNA damage and promotes genomic instability

• DNA integration - some viruses can integrate their genetic material into the host genome, potentially disrupting genes and activating oncogenes

• viruses encode proteins that can damage host signalling mechanisms that regulate growth and survival, leading to inhibition of cell death and enhanced proliferation

describe the process of EBV mediated lymphomagenesis

1. EBV infects B cells

2. infected B cells evade immune detection by entering a latency phase

3. EBV expresses different latent viral genes that contribute to lymphomagenesis such as EBNA 1,2 and 3

describe the process of HPV mediated cervical carcinogenesis

• HPV infects basal epithelial cells in the cervix

• HPV E6 protein binds to p53 and promotes it degradation, preventing apoptosis and leading to uncontrolled cell growth

• HPV E7 binds to and inactivates Rb, leading to continuous cell division

describe the process of HBV mediated hepatocellular carcinoma

• chronic hepatitis causes persistent inflammation - cytokines and oxidative stress promote DNA damage and genomic instability

• virus integrates into the host genome, leading to genomic instability

• hepatitis B X protein disrupts p53 function, allowing uncontrolled cell proliferation

describe the process of HCV mediated hepatocellular carcinoma

• chronic hepatitis causes persistent inflammation - cytokines and oxidative stress promotes DNA damage and genomic instability

• HCV core protein alters cell cycle regulation, promotes oxidative stress and disrupts tumour suppressor genes

describe the process of HTLV-1 induced adult T cell leukaemia

• HTLV-1 genome encodes a protein called tax - oncogenic protein that promotes the survival and proliferation of infected T cells

• over time, infected T cells accumulate mutations in other genes that further promote cancerous transformation

describe the HPV vaccines

• recombinant vaccine containing purified virus like particles obtained from the major capsid (L1) protein of different HPV serotypes

• the inactive HPV L1 VLPs in the vaccines produce neutralising antibodies against HPV types

what is oncolytic virotherapy

• cold tumours are poorly infiltrated by immune cells and have low expression of PD-L1 on cancer cell surface - means they have a poor response to immune checkpoint inhibitors

• oncolytic virotherapy promotes a strong antiviral immune response accompanied by the production of cytokines which stimulate PD-L1 expression on the surface of cancer cells - means will have a better response to immune checkpoint inhibitors

describe how gallbladder cancer is induced by salmonella typhi

• produces cytolethal distending toxin which induces DNA damage and genomic instability in gallbladder epithelial cells

• intoxicated cells are prone to die unless salmonella stimulates damaged cells to survive

describe the mechanisms of induction of Burkitt lymphoma by falciparum malaria

• causes chronic immune activation and B-cell expansion (including those B cells infected with EBV)

• weakens T cell surveillance leading to reactivation of EBV and uncontrolled infected B cell proliferation

• impairs EBV-specific T cell response, allowing EBV infected B cells to escape immune surveillance and progress towards malignancy