The HIV protease inhibitor lopinavir (a component of Kaletra) triggers
cells infected with human papillomavirus to produce an antiviral protein,
inducing death of the cancerous cells, researchers at the University of Manchester
report in the journal Antiviral Therapy.
“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
The finding could lead to a new form of treatment for
cervical cancer, which is caused by certain high-risk types of human
At present treatment options for precancerous lesions caused
by human papillomavirus, and for cervical cancer, are limited to freezing with
liquid nitrogen in early stages, to electrocauterisation, or to surgery and
chemotherapy in cases of cervical cancer.
However, in low and middle-income settings surgical
treatments for precancerous lesions and for cervical cancer are often more
difficult to deliver due to limited screening programmes, a lack of surgically
trained staff and lack of medicines. Due in part to these obstacles, cervical
cancer is the most common malignancy in women in sub-Saharan Africa.
Treatments which can be delivered easily by nurses and by
affected women, starting on the day when a precancerous lesion is identified,
could be particularly important in reducing progression to cervical cancer and
deaths from cervical cancer in the developing world.
Although HPV vaccination is being introduced in some
countries it cannot protect women who have already developed precancerous
changes or who have been infected by high-risk HPV types that are not included
in the two vaccines now available.
More generally, a drug which is effective against HPV could
revolutionise the prevention of anal and oral cancers caused by HPV.
of Manchester researchers
tested the effect of lopinavir on HPV-infected cells derived from cervical
cancer and from human foreskin.
They found that lopinavir increased the production of
ribonuclease L in cells infected with cancer-causing HPV types. HPV appears to
reduce the expression of ribonuclease L, but the process which HPV reduces
Ribonuclease L expression is inhibited by lopinavir.
The authors also speculate that the same process could lower
host antiviral defences and so permit infection with other viruses, indicating
a possible explanation for the association between HPV infection and subsequent
risk of HIV infection in men
and in women.
Co-author on the paper, Dr Lynne Hampson, said: “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 defence
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
Standard dose Kaletra
treatment in women with HIV is unlikely to show an association with a reduced
risk of cervical cancer due to the dose needed to kill HPV-infected cells.
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 10-15 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.”