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|Title: ||study on virological and immunological factors involved in determining the course of HPV anogenital infection|
|Authors: ||CANNELLA, FABIANA|
|Tutor: ||Antonelli, Guido|
|Issue Date: ||12-Feb-2013|
|Abstract: ||Infection by high-risk HPV types is necessary but not sufficient for
progression to cancer. In fact, the majority of HPV infections do not lead to
cytological anomalies or cancer but only a small percentage (10-15%)
persist and promote the development of low and high-grade lesions.
It is known that to persist HPV must escape the host immune system and
persistence could be due to an impaired IFN-system activation in the
In literature, most studies were conducted in cell lines with constitutively
oncogenes expression, whereas in vivo, the majority of HPV infections that
resolve with time have a transient oncogene expression. To clarify the role
of innate immune response, we analysed, for the first time, the expression of
several TLRs (TLR2, TLR3, TLR4, TLR7 and TLR9), the IFN lambda
pathways (INF-lambda 1, INF-lambda II, the IFN-lambda receptors), and
the activation of several IFN induced genes (ISG15, MxA and p56) in HPV
positive and negative cervical cells from 154 patients.
The expression levels of TLR2, TLR3, TLR4 and TLR7 resulted highly
variable both in HPV negative and in HPV positive patients.
Differently, TLR9 was activated at different levels during HPV infection,
with a tendency to be higher in LR-HPV infected women and significantly
higher in patients with HPV persistent infection.
Furthermore, we correlated TLRs expression with histological grade of
lesions; TLR7 and TLR9 increased with the histopathological grade, but
TLR9 in patients with persistent HPV infection was greater then in patients
with CIN II or worse lesion, independently of lesions grade
We hypothesize that the inability to clear HPV DNA after one year could be
a risk factor to later develop high-grade lesions due to the persistence of the
virus and the high levels of TLR9.
IFN lambda 1 was expressed at higher level in patients with LR HPV
infection compared to HR HPV and negative and we observed the same
trend for IFN lambda 2/3. The elevated expression level of IL28R in
patients with LR HPV infection respect to the other study groups confirmed
the data obtained with IFN-lambda.|
|Research interests: ||Human Papillomavirus, immunology, IFN system|
|Personal skills keywords: ||Molecular biology|
|Appears in PhD:||MEDICINA SPERIMENTALE|
Files in This Item:
|TESI DOTT. FABIANA CANNELLA.pdf||PhD thesis||7.14 MB||Adobe PDF|
File del Curriculum Vitae:
|CurriculumVitae.docx|| ||120.31 kB||Microsoft Word XML|
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