The HPV16 oncogenes cause aberrant stem cell mobilization

Abstract

Human Papilloma Virus related epithelial cancers have been speculated to derive from virus-infected tissue stem cells. Stem cells also are thought to provide a reservoir of latently infected cells that can persist for long periods. In this study we have examined the effects of HPV16 E6 and E7 oncogenes on multipotent epithelial stem cells, using in vivo systems. Our results show that expression of HPV16 oncogenes reduces the number of bulge label-retaining cells within hair follicles at telogen suggesting aberrant mobilization, a result supported by increased mobilization upon acute anagen induction. Importantly the loss of relative quiescence, a hallmark feature of stem cells, occurs in the absence of a reduction in other stem cell markers. This points to an atypical stem cell compartment in the context of E6 and E7 expression. We hypothesize that this aberrant compartment may have important roles in the viral life cycle and/or ensuing carcinogenesis.