HPV infections caused an estimated 266,000 deaths from cervical cancer worldwide in 2012, according to the World Health Organization. Routine screening by Pap smears or HPV DNA tests has reduced death rates in developed countries compared to less developed regions of the globe.
Highly efficacious vaccines against HPV infection exist — including the recently approved Gardasil 9, which immunises against nine genotypes of HPV known to cause cervical, vulvar, vaginal and anal cancers, and genital warts. But the vaccine needs to be given before a person becomes sexually active, since it has no therapeutic efficacy against existing HPV infections, the researchers said.
Preclinical experiments by researchers at University of Alabama at Birmingham (UAB) in the US suggest the cancer drugs vorinostat, belinostat and panobinostat might help treat HPVs.
“Safe, effective and inexpensive therapeutic agents are urgently needed,” said lead author N. Sanjib Banerjee, Assistant Professor at UAB.
In the study, detailed in the journal PNAS, the team discovered that the productive programme of HPV depends on differentiation of the epithelium into a full-thickness, squamous epithelium.
Furthermore, HPV reactivates host DNA replication in these differentiated cells such that the replication proteins and substrates become available to support viral DNA amplification.
They found that vorinostat effectively slowed down HPV-18 DNA and virus production. Importantly, vorinostat also induced the programmed cell death in a fraction of the differentiated cells. Similar results were obtained with belinostat and panobinostat.
The UAB team also reported that vorinostat caused extensive cell death in raft cultures of dysplastic and cancer cell lines harbouring HPV-16.
HPV-16 and HPV-18 are the most prevalent, high-risk HPVs responsible for causing anogenital — the cervix, penis and anus — and oropharyngeal — mouth and throat — cancers.
“But further investigation would be required to verify that these agents could also be useful in treating HPV associated dysplasias and cancers,” Banerjee said.