Epstein-Barr virus (EBV) infects over 90% of the world's population and is associated with several cancers. EBV is transmitted through bodily fluids and causes infectious mononucleosis. While most infections are asymptomatic, EBV can establish lifelong latent infections and has been linked to Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma among other cancers. Burkitt's lymphoma is an aggressive B-cell lymphoma associated with EBV in 80% of endemic cases and 20% of non-endemic cases. Up to 40% of Hodgkin's lymphoma cases are also associated with EBV infection of the Hodgkin Reed-Sternberg cells.

1. EBV and Carcinogenesis

2. What is EBV?
• Epstein-Barr virus (EBV), also known as human herpesvirus 4 (or the
kissing disease), is a member of the herpes virus family. It is one of the
most common human viruses. EBV is found all over the world. EBV
can cause infectious mononucleosis Most people get infected with EBV
at some point in their lives,
• The majority of infections occur early in life without significant illness.
However, EBV is clearly an important factor in multiple human
cancers
• that is a ubiquitous infectious agent, infecting greater than 90% of the
world’s population.

3. How is EBV transmitted?
• EBV spreads most commonly through bodily fluids,
especially saliva. However, EBV can also spread through
blood and semen during sexual contact, blood transfusions,
and organ transplantations. EBV can be spread by using
objects, such as a toothbrush or drinking glass, that an
infected person recently used. The virus probably survives on
an object at least as long as the object remains moist.

4. EBV is spread by saliva through:
• kissing
• sharing drinks and food
• using the same cups, eating utensils, or toothbrushes
• having contact with toys that children have drooled on

5. Symptoms of EBV infection?
• fatigue
• fever
• inflamed throat
• swollen lymph nodes in the neck
• enlarged spleen
• swollen liver
• rash

7. How does EBV cause cancer?
• The ability of EBV to cause cancer is most clearly indicated
by the development of B-cell lymphoproliferations in patients
who are deficient in T-cell mediated immunity following bone
marrow or solid organ transplantation. The majority of cases
of post-transplant lymphoma (PTL) are EBV-positive.
• the virus establishes a latent infection with life-long
persistence in the infected host,Virus expression is tightly
restricted in latently infected B-lymphocytes with no viral
gene expression or with expression limited to the EBV
nuclear antigen 1 (EBNA1), and/or latent membrane protein
2 (LMP2).

8. The state of EBV latency may reactivate and express additional viral
genes that induce cell growth, including the other EBNAs and LMP1 and
LMP2. The proliferation of the infected lymphocytes is controlled by
cytotoxic T-cells (CTLs) that primarily recognize the EBNA2 and EBNA3
proteins. Therefore in immunosuppressed patients who lack CTL control,
EBV-infected B-lymphocytes may proliferate and develop into B-cell
lymphomas
The majority of the infected cells in the cell lines do not produce virus
but instead are latently infected and maintain the EBV genome as a
multi-copy episome. In vitro, an occasional cell in some cell lines may
reactivate into viral replication and produce infectious virus.The ability
of the virus to efficiently transform B-cells in culture to immortalized,
transformed cells undoubtedly underlies its connection to human
cancers. In B-cell lines grown in vitro, the carefully regulated, coordinate
expression of multiple viral gene products induces permanent continuous
cell growth

10. The setting for occcurence of EBV associated malignancies?
• Immunosuppression
• Endemic areas
• Environmental and genetic factors may have a role in the
formation of cancers

11. What are types of cancer produced by EBV?
• Burkitt's lymphoma
• lymphomas in immunosuppressed patients
(HIV infection or organ transplant recipients)
• Hodgkin's lymphoma subset
• Nasopharyngeal Carcinoma
• Uncommon T cell and NK cell tumors
• A subset of gastric carcinoma,
• Rarely sarcomas

12. Firstly and most importantly ( Burkitt's lymphoma)
• What is Burkitt's lymphoma? Burkitt's lymphoma is an
aggressive form of lymphoma that affects the B-lymphocytes. It
accounts for approximately 0.3-1.3% of all non-Hodgkin
lymphomas. Burkitt's lymphoma is relatively rare in Western
countries, but is quite common in Central Africa
• Burkitt lymphoma is a rare but highly aggressive (fast-growing)
B-cell non-Hodgkin lymphoma (NHL). This disease may affect the
jaw, central nervous system, bowel, kidneys, ovaries, or other
organs. Burkitt lymphoma may spread to the central nervous
system (CNS).
•

15. BL cells show a reciprocal translocation between the long arm
of
chromosome 8 and chromosomes 14, 2 or 22.
This translocation result in the c-myc oncogene being
transferred to the Immunoglobulin gene regions. This
results in the deregulation of the c-myc gene. It is
thought that this translocation is probably already
present by the time of EBV infection and is not caused
by EBV.
• Pathogenesis

16. • Burkitt's lymphoma is associated to EBV with a percentage
of 80% in endemic areas
• Burkitt's lymphoma is associated to EBV with a percentage
of 20% in Non Endemic area.

17. Types of burkitt lymphoma
• Endemic burkitt lymphoma
• Sporadic burkitt lymphoma
• Immunodeficiency related burkitt lymphoma

18. Treatment of burkitts lymphoma
Burkitt lymphoma is usually treated with a number of
different chemotherapy drugs and a targeted immunotherapy
drug called rituximab (Mabthera). You might hear this
combination called chemoimmunotherapy. Your treatment can
be very intensive lasting several months. You might be in
hospital for a lot of this time.

19. Hodgkin lymphoma and EBV
• Up to 40% of Hodgkin lymphoma (HL) cases are associated
with the Epstein-Barr virus (EBV).
Epidemiology
• It is more frequent in cases with mixed cellular histology, in
males, in children and older adults
• and in developing countries, while the young-adult onset HL
of nodular sclerosis type in industrialized countries is
typically EBV-negative. Countries in the Mediterranean area
often show an EBV positive result.

20. How is Hodgkin lymphoma caused?
• Clonal viral genomes can be found in the HL tumor cells, the
Hodgkin Reed-Sternberg cells (HRS). The latent infection
results in expression of the viral oncogenes LMP1 and
LMP2A which contribute to generate the particular
phenotype of the HRS cells. EBV does not only undergo
epigenetic changes of its genome during latency, but also
induces epigenetic changes in the host genome. The presence
of EBV may alter the composition and activity of the immune
cells surrounding the HRS cells. EBV favours a Th1 reaction,
but this attempt at a cell mediated immune response
appears to be ineffective.

21. • Hodgkin’s disease is characterized by a rare population of
Hodgkin Reed-Sternberg (HRS) cells which are surrounded
by a massive inflammatory infiltrate. The paucity of the HRS
cells hampered their biological characterization1