Modulation of oral cancer phenotypes by human papillomavirus

Objectives: The detection of human papillomavirus (HPV) in oral cancers suggests it may function to transform oral epithelia, as it does in cervical epithelia. Recent studies revealing the presence of HPV in nearly half of oral cancers, compared with only ten percent in normal oral tissues, suggest that it may also play a role in modulating the phenotypes of already developing tumors. The objective of this study, therefore, was to test the hypothesis that high-risk HPV strains, commonly detected in oral cancers, are sufficient to alter the phenotypic behaviors of transformed oral squamous cell carcinomas (OSCC).

Methods: Using several well-characterized cell lines, CAL27, SCC-15, SCC-25, HGF-1 and Hs27, in vitro assays were used to measure cellular proliferation responses among cancerous and non-cancerous cell lines following transfection with the high-risk HPV strains, HPV16 and HPV18.

Results: Both HPV16 and HPV18 were sufficient to induce marginal increases in cell proliferation among the non-cancerous controls, HGF-1 and Hs27. However, differential responses to these HPV strains were evident among the oral cancer cell lines. For example, HPV16 induced significant and proportionally greater increases in proliferation among CAL27 and SCC-25 cell lines, compared with non-cancerous controls. HPV18 induced significant and proportionally greater increases in proliferation among the CAL27 and SCC-15 cell lines, compared with non-cancerous controls.

Conclusion: These studies are among the first to investigate the comparative effects of high-risk HPV infection on the phenotypic behaviors of normal and cancerous oral cell lines. These data represent a critical first step in the elucidation of the mechanisms responsible for these differential phenotypic alterations.