The LICR team is studying the nucleotide sequence variations of two different oncogenic HPV strains, HPV-16 and HPV “18, as a tool for epidemiological studies of viral transmission and persistence. The team has found that intratypic sequence variations in HPV-16 are an important predictor of progression from benign to malignant cervical lesions. The investigators also found that non-European ™ sequence variants of HPV-16 and HPV-18 were more strongly associated with risk of cervical neoplasia than European ™ variants, when compared with other oncogenic HPVs and low oncogenic risk HPVs. The realization that non-European variants of HPV-16 and HPV-18 may confer increased oncogenic risk may explain why there is a disproportionately high incidence of cervical cancer in different regions of the world that are populated by non-European ™ races.

Sequence differences in the HPV genomes are important for determining the infectious potential of different variants, but they are also very important for identifying antigenic epitopes for HPV vaccines. Antigenic epitopes are protein sequences in HPV strains that are recognized, and thus targeted, by the immune system. Little is known about the influence of different HLA molecules (HLA haplotypes) in an individual ™s immune response to HPV. Each HLA molecule presents specific protein fragments for recognition by the immune system, and the LICR team has found that susceptibility to cervical cancer has been associated with the presence and absence of certain HLA haplotypes. In fact, the LICR ™s studies suggest that different HLA haplotypes are involved in genetic susceptibility to squamous cell carcinoma (SCC) as well as HPV infection in Brazilian women. Understanding the role that certain HLA molecules play in immune responses against HPV infections and subsequent cervical carcinogenesis will help to develop better approaches for preventing and treating cervical cancer through vaccination and immunotherapy, respectively.

Recently, LICR, through its S o Paulo Branch, partnered with Merck, Sharp & Dohme to coordinate a Phase II trial in Brazil for a Quadrivalent HPV Vaccine designed to induce immune recognition of four HPV strains (HPV-6, -11, -16, and -18). The first analysis has been conducted, and the team is currently implementing Phase III efficacy programs for the HPV vaccine. If proven safe and effective, a vaccine that prevents infection with common pathogenic HPV types will be a major advance in the control of anogenital (anal, cervical, and penile) cancers.