Regulation of Papillomaviral DNA Replication in Epithelial Cells

1
Regulation of Papillomaviral DNA Replication in
Epithelial Cells
Deregulation of Cell-growth Proliferation Differe
ntiation Programmed cell death
2
E6 Dependent Degradation of p53
p53 ubiquitin (n)
3
Relaxation of G1/S Cell Cycle Control by HPV E7
4
HPV E5 Increases the Cell Surface EGFR
Concentration
5
Development of HPV Associated Cervical Neoplasia
Transient HPV infection
Persistent HPV infection with high-risk types
Cervical infraepithelial neoplasia
Invasive cervical cancer
Sexual
Normal mucosa
Activity
Cofactors smoking, OC use, parity, other STDs
6
Hepatitis B Virus-I
Hepatitis B acute and chronic infection In USA in
95 of cases hepatitis B virus is cleared after
acute infection, while in the 5 the virus will
persist and the individuals will become carriers.
There is an association between the rate of the
carrier state and hepatocellular carcinoma. In
countries where the carriage rate is high(10-20
PR of China, Taiwan, parts of the Far East),
then hepatocellular carcinoma is also common. An
additional factor is that in these countries the
virus is transmitted to the neonate, at birth, or
early in life through close contact with the
mother this is associated with a very high rate
of chronic virus infection. Transmission Routes
of transmission include blood, milk and possibly
saliva, sexual transmission.
7
Hepatitis B Virus-II

• Proof of association with cancer
• PROSPECTIVE STUDIES persons who are HBV have
  over a 200-fold increase to develop liver cancer,
  compared to persons who are HBV-.
• The incidence of chronic viral infection and HCC
  is restricted to the same areas.
• Virus DNA is detected in gt85 of tumors, in an
  integrated state.
• Natural infection of animals with hepadnaviruses
  is associated with PHC.
• Note There is a long incubation period before
  development of hepatocellular cancer usually
  four to five decades.
• Cocarcinogens
• Aflatoxin B1/p53 point mutation (249ser)
• Alcoholism

8
Possible Mechanisms of Hepatocellular Carcinoma
Formation Due to HBV Infection