HIV drug could lead to new cervical cancer treatment
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 Sciences.
The finding could lead to a new form of treatment for cervical cancer, which is caused by certain high-risk types of human papillomavirus. 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.
The University 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 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 the cervix.”
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.”