Infection associated cancers are increasing at an alarming rate. Human papillomavirus (HPV) infection is estimated to cause one-third of the 1.5 million cancers attributed to viruses. The HPV related cancers include cervical cancer, head and neck squamous carcinoma, and anal cancer. Our long-term goal is to understand the basic processes that are necessary to establish HPV infection. Understanding the process of initial viral entry and trafficking can result in novel approaches to decrease infection and lessen the burden of HPV related cancers.
One of the limiting factors in the worldwide effort to reduce papillomavirus induced diseases including genital and anal cancers is the inability to target the many identified genotypes with current vaccine efforts. The current HPV vaccine against two oncogenic (16 and 18) and two non-oncogenic (6 and 11), or the two oncogenic (16 and 18) genotypes, target poorly conserved capsid surface L1 epitopes (Merck & Co., GSK respectively). HPV16 and 18 are two of the more than thirteen oncogenic genotypes. These vaccines prevent the binding of viral particles to target cells. Caveats of these efforts are that over 30-40% of the HPV related cancers are associated with HPV genotypes not covered by the vaccine, and that these vaccines are cost-prohibitive in underdeveloped countries where incidences of cervical carcinoma are the highest. These facts highlight the need for a low-cost, broad-acting antiviral.
Our studies focus on the binding, endocytosis, and intracellular trafficking events that result in the nuclear translocation of the viral DNA. We believe that understanding these steps will lead to antiviral approaches that will target a broader spectrum of PVs. We also believe that our findings will identify molecules or steps that will be amenable to disruption by means of peptide antibodies or small molecules whose cost will be lower than those of the current vaccines.