Infections cause various malignancies like hepatic malignancy associated with Hepatitis B and C virus. This PPT will provide basic details regarding pathogenesis and mutations in infection induced malignancies.

1. Infection and cancer
DR. KEERTHANA D
DEPARTMENT OF GENERAL MEDICINE

2. Properties of
malignant cells

3. Infections causing cancer
 Infections account for 15 to 20% of all malignancies, worldwide.
 Preventable cause of malignancy.
 Viral infection – most common. It causes malignancy by
1. Production of Viral oncoproteins
2. By mutation of proto-oncogenes
3. By viral insertion
4. By chronic inflammation and tissue damage

4. Viral oncoproteins

5. Mutation of proto
oncogenes

7. Properties of oncogenic viruses
 Causes chronic infection
 Evade host immunity
 Long latency between the infection and development of malignancy.

8. RNA virus
 Human T cell Lymphotropic virus 1
(HTLV1)
 Hepatitis C virus
DNA virus
 Human Papilloma virus (HPV)
 Epstein-Barr virus (EBV)
 Kaposi Sarcoma Herpes virus (KSHV)
 Hepatitis B virus

9. Human Papilloma Virus
 HPV 6 and 11 – low malignant potential. Associated with Genital warts.
 HPV 16 & 18 – high malignant potential. Causes squamous cell carcinoma of
cervix and Anogenital region.
 20% of oropharyngeal malignancies are also associated with HPV infection.
 By production of oncoproteins – E6 and E7.
 E7 –binds to retinoblastoma protein (Rb)
 E6 – binds to p53 and facilitates degradation of p53.

11.  E6 and E7 from HPV 16 &18 (high risk HPV) has highest affinity for p53 and Rb
protein.
 HPV infection causes malignancy by,
1. Activation of cyclins
2. Inhibition of tumor suppressors ( p53, p21, p27)
3. Inhibition of apoptosis

12. Epstein Barr virus
 Human Herpes virus 4
It causes,
 Burkitt lymphoma ( Bcell lymphoma)
 Nasopharyngeal carcinoma
 Hodgkin lymphoma ( mixed Cellularity type)
 Sarcomas

13.  EBV infects B cells via CD 21 receptor.
 Latent Membrane Protein 1 ( LMP1) – EBV encoded gene and it promotes B- cell
proliferation by activating JAK/STAT and NF-kB pathways
 Translocation between chromosome 8 and 14, which causes overexpression of
MYC proto oncogene.
 Immunocompetent patients – asymptomatic or self limited disease.
 In Immunosuppressive conditions such as concomitant malaria or other infections
– causes sustained B cell proliferation.

16. Kaposi sarcoma
 Angio-proliferative spindle cell tumor –
derived from endothelial cells and
immune cells.
 Human Herpes Virus 8 infection.
 Lesions are seen in skin, oral mucosa,
lymph nodes, and visceral organs

18.  Types :
1. Classic – occurs as sporadic infection, progressive over 10 to 15 years.
2. Endemic - common in African countries
3. Epidemic or AIDS related ( CD4 <500cells/cu.mm)
4. Iatrogenic – organ transplant related

19. Symptoms
 Cutaneous lesions
 Cough, dyspnea, hemoptysis, chest pain
 Odynophagia, nausea, hemetemesis, hematochezia, bowel obstruction

20. Hepatitis B and C virus

22. Mechanism
 Activation of NF-kB pathway (By mediators from immune cells) – inhibits
apoptosis
 Chronic inflammation and tissue damage
 Production of reactive oxygen species
 Accumulation of mutation and will result in malignant proliferation

24. Helicobacter pylori
 Gastric adenocarcinoma
 Gastric MALToma
 CagA gene is injected into the gastric epithial cells and causes unregulated growth
signals.
Pathology:
1. Chronic inflammation and tissue damage
2. Increased epithelial cell proliferation

27. Genetic basis of malignancies

28. Multiple Endocrine Neoplasia

MEN 1 syndrome or Wermer syndrome MEN 2 syndrome or Sipple’s syndrome
Mutation:
MEN 1 gene on chromosome 11 RET proto oncogene mutation
1. Pituitary adenoma
2. Hyperparathyroidism
3. Pancreatic neuroendocrine tumours
1. Medullary carcinoma thyroid
2. Pheochromocytoma
3. Parathyroid tumors

33. Summary
 HPV – causes cervical cancer. Produces oncoproteins E6 and E7 which binds to
p53 and Rb gene.
 EBV – Various B cell lymphomas, Nasopharyngeal carcinoma
 Hepatitis B and Hepatitis C – causes chronic hepatitis and cirrhosis. Malignancy
occurs in untreated patients as a result of chronic inflammation.
 HTLV1 – retrovirus (like HIV) infects CD4 cells and causes T cell leukemia

34.  H. Pylori – CagA gene. Causes gastric adenocarcinoma and MALToma
 MEN syndromes – MEN 1 ( chromosome 11) and MEN 2 – RET proto oncogene.
 BRCA 1& 2 – breast cancer
 Rb gene – retinoblastoma
 APC gene – Familial adenomatous polyps or colon cancer