Srpski arhiv za celokupno lekarstvo 2014 Volume 142, Issue 5-6, Pages: 378-383
https://doi.org/10.2298/SARH1406378Z
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Persistent human papillomavirus infection in the etiology of cervical carcinoma: The role of immunological, genetic, viral and cellular factors
Živadinović Radomir (Clinical Center, Clinic of Gynecology and Obstetrics, Niš)
Petrić Aleksandra (Clinical Center, Clinic of Gynecology and Obstetrics, Niš)
Lilić Goran (Clinical Center, Clinic of Gynecology and Obstetrics, Niš)
Lilić Vekoslav (Clinical Center, Clinic of Gynecology and Obstetrics, Niš)
Đorđević Biljana (Clinical Center, Institute for Pathology, Niš)
The aim of this paper was to present the role of human papillomavirus (HPV)
in cervical carcinogenesis from several aspects. By explaining the HPV virus
lifecycle and structure, its effect on cervical cell cycle and subversion of
immune response can be better understood. Early E region of the viral genome
encodes proteins that are directly involved in carcinogenesis. The E6 protein
binds to p53 protein (product of tumor-suppressor gene) blocking and
degrading it, which in turn prevents cell cycle arrest and apoptosis
induction. E6 is also capable of telomerase activation, which leads to cell
immortalization; it also reacts with host proto-oncogene c-jun, responsible
for transcription, shortens G1 phase and speeds up the transition from G1 to
S phase of the cells infected by HPV. E7 forms bonds with retinoblastoma
protein (product of tumor-suppressor gene) and inactivates it. It can
inactivate cyclin inhibitors p21, p27, and abrogate the mitotic spindle
checkpoint with the loss of protective effect of pRB and p53. The immune
system cannot initiate early immunological reaction since the virus is
non-lytic, while the concentration of viral proteins - antigens is low and
has a basal intracellular position. Presentation through Langerhans cells
(LC) is weak, because the number of these cells is low due to the effect of
HPV. E7 HPV reduces the expression of E-cadherin, which is responsible for LC
adhesion to HPVtransformed keratinocytes. Based on these considerations, it
may be concluded that the process of cervical carcinogenesis includes viral,
genetic, cellular, molecular-biological, endocrine, exocrine and
immunological factors.
Keywords: human papillomavirus (HPV), cervical carcinogenesis, cell cycle