May 4, 2011
The HIV drug lopinavir is selectively toxic to human papillomavirus-positive cervical cells, a new study suggests. About 3,000 UK women are diagnosed with cervical cancer annually, mostly due to HPV infection by high-risk strains, which have also been linked to oral cancers.
Previous laboratory cell cultures found the protease inhibitor killed HPV-infected cells but left healthy cells relatively unharmed. In the new study, Dr. Ian Hampson, of the University of Manchester, and Canadian colleagues concluded that lopinavir's toxicity is related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein Ribonuclease L.
"Lopinavir kills these HPV-infected cells by reactivating a well-known antiviral system that is suppressed by HPV," Hampson said. "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 precancerous HPV infection of the cervix," Hampson said.
However, an effective treatment would need to be administered at a dosage 10-15 times that taken by HIV patients. That could require a cream or vaginal insert rather than oral formulation, said Hampson.
"These results are very exciting since they show that the drug not only preferentially kills HPV-infected non-cancerous cells by reactivating known antiviral defense systems, it is also much less toxic to normal non-HPV-infected cells," said study co-author Dr. Lynne Hampson. "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 study, "Lopinavir Up-Regulates Expression of the Antiviral Protein Ribonuclease L in Human Papillomavirus-Positive Cervical Carcinoma Cells," was published online ahead of the print edition of Antiviral Therapy (2011; doi:10.3851/IMP1786).