HPV integration into host epithelial cell DNA can cause overexpression of E6 and E7 oncoproteins from high-risk HPV strains. E6 degrades p53 and activates telomerase while E7 binds and deactivates RB, inactivating cell cycle controls and inducing immortalization, excessive proliferation and genomic instability. EBV infects and stimulates proliferation of B lymphocytes and epithelial cells, potentially causing cancers like Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's lymphoma. HHV-8 infection is associated with Kaposi's sarcoma through overexpression of latency proteins like v-cyclin and LANA that increase host cell proliferation and survival.

1. HPV Oncogenesis
 On persistence of infection with high risk HPV types, the viral DNA is integrated
into the target epithelial cells.
 This results in genomic instability of the host cell leading to loss of E2 viral
repressor and overexpression of viral oncoproteins E6 and E7.
 These oncoproteins(E6 and E7) from high risk HPVs have high affinity for target
hosts cell than these oncoproteins from low risk HPVs.
 Transforming effects of HPV are largely due to alteration in genes encoding E6 and
E7 oncoproteins as followings

2. HPV-E6 Degrades TP53 Blocks apoptosis TERT overexpressed
(Tumor- suppressor
inhibited)
HPV-E7 Binding to RB Inactivates p21, p27 Activates cyclin D, C,CDK4
(RB- E2F
Displaced)
(CDK Inhibiters)
Oncogenic Effects of E6
Oncogenic Effects of E7
• Immortalization
• Excessive proliferation
• Genomic instability
• Immortalization
• Excessive proliferation
• Genomic instability

3. EPSTEIN-BARR VIRUS(EBV)
 EBS infects human B-lymphocytes and epithelial cells and long-term infection
stimulates them to proliferate and develop into malignancies of corresponding
cells. EBV is implicated in the following human tumours:
i. Burkitt lymphoma,
ii. Anaplastic nasopharyngeal carcinoma,
iii. Post-transplant lymphoproliferative disease,
iv. Primary CNS lymphoma in AIDS patients, and
v. Hodgkin lymphoma

4. Burkitt Lymphoma
 Burkitt lymphoma was initially noticed in African children by Burkitt in 1958 but is
now known to occur in 2 forms.
 African endemic form
 Sporadic form (seen else where in world)
 It usually occurs in children in between the age of 3-14 years. It responds favorably
to chemotherapy.
 The association between Burkitt lymphoma and EBV is observed from the following
features.
 Over 90% of Burkitt lymphomas are EBV-positive in which the tumour cells carry the viral
DNA.
 100% cases of Burkitt lymphoma show elevated levels of antibody titres to various EBV
antigens.
 EBV has strong tropism for B lymphocytes. EBV-infected B cells grown in cultures are
immortalizes, i.e. they continue to develop further along B-cell-line to propagate their
progeny in the altered form.

5. EBV-induced oncogenesis
B lymphocyte
(EBV-infected)
Cell proliferation
dysegulated
(CD40-like effect)
LMP1 expressed Activates BCL2
Growth signalling
Prevents apoptosis
Epithelial cell
(EBV-infected)
Elaborates EBNA-2
(via NF-kB, JAK/stat pathway)
Activates cyclin
D,SRC family
Stimulates B-cell
proliferation
Burkitt Lymphoma
Nasopharyngeal
carcinoma

7. Anaplastic nasopharyngeal carcinoma
 This is the other tumour having involvement of EBV infection.
 The tumour is prevalent in South-East Asia, especially in the Chinese, and in
Eskimos.
 The evidence linking EBV infection with this tumour is as follows:
i. 100% cases of nasopharyngeal carcinoma carry DNA of EBV in nuclei of tumour cells.
ii. Individuals with this tumour have titres of antibodies to various EBV antigens.

8. HUMAN HERPESVIRUS 8 (HHV-8)
 It has been shown that infection with HHV-8 is associated with Kaposi sarcoma, a
vascular neoplasm common in patients of AIDS.
 Hence also called Kaposi sarcoma-associated herpesvirus(KSHV).
 Compared to sporadic Kaposi sarcoma, the AIDS-associated tumour is multicentric
and more aggressive.
 HHV-8 has lymphotropism and is also implicated in etiology of pleural effusion
lymphorma and multicentric variant of Castleman disease.

9. HHV-8 (KSHV) ONCOGENESIS
 This is explained as under:
i. Viral DNA is seen in nuclei of all tumour cells in Kaposi sarcoma.
ii. There is overexpression of several KSHV oncoproteins by latently infected cells: v-
cyclin, v-interferon regulatory factor(v-IRF) and LANA(latency-associated nuclear
antigen).
iii. These viral proteins cause increased proliferation and survival of host cells and
thus induce malignancy.