Photo: Univ. of Manchester |
Univ. of Manchester
researchers, working with colleagues in Canada, have discovered how the
antiviral drug lopinavir attacks HPV by switching on a natural viral defense
system in infected cells.
The study, published in Antiviral Therapy, builds on the team’s
previous work in 2006 that first identified lopinavir as a potential
therapeutic for HPV-related cervical cancer following laboratory tests on cell
cultures.
“Since publishing our earlier
work, we have now found that lopinavir selectively kills HPV-infected,
non-cancerous cells, while leaving healthy cells relatively unaffected,” said
Dr. Ian Hampson, from Manchester’s School of Cancer and Enabling Sciences.
“This is a very significant
finding as these cells are not cancer cells but are the closest thing to being
like the cells found in a pre-cancerous HPV infection of the cervix. In
addition we were also able to show that lopinavir kills these HPV-infected
cells by re-activating a well-known antiviral system that is suppressed by
HPV.”
In many developing countries,
HPV-related cervical cancer is still one of the most common women’s cancers
accounting for approximately 290,000 deaths per year worldwide. The same virus
also causes a significant proportion of cancers of the mouth and throat in both
men and women and this disease is showing an alarming increase in developed
countries, such as the UK,
where it is now more than twice as common as cervical cancer.
Although in the developed world
vaccination programs against HPV are well underway, these are not effective in
women already infected with HPV. Furthermore, the current vaccines do not
protect against all types of HPV and they are expensive, which will limit their
use in countries with limited resources. A cheap and preferably self-administered
treatment that could eliminate early-stage HPV infections before these have
developed into cancers would therefore have distinct health advantages.
Dr Hampson said: “Our results
suggest that for this drug to work against HPV it would be necessary to treat
virus-infected cells of the cervix with roughly 10 to15 times the concentration
that is normally found in HIV-infected patients taking lopinavir as tablets.
This implies that, for this treatment to work, it would need to be locally
applied as a cream or pessary.”
Co-author on the paper, Dr. Lynne
Hampson, added: “These results are very exciting since they show that the drug
not only preferentially kills HPV-infected non-cancerous cells by re-activating
known antiviral defense systems, it is also much less toxic to normal non-HPV
infected cells.
“Lopinavir is obviously safe for
people to take as tablets or liquid but our latest findings provide very strong
evidence to support a clinical trial using topical application of this drug to
treat HPV infections of the cervix.”
The research in Manchester was carried out by the Hampsons’
PhD student, Gavin Batman, who was funded by the Humane Research Trust charity,
with additional funding supplied by the Caring Cancer Trust and the Cancer
Prevention Research Trust.