Association between hTERT activation by HPV E6 proteins and oncogenic risk

Expression of activated telomerase and subversion of the p16/pRb pathway is sufficient and essential for the in vitro immortalization of primary keratinocytes. Most cancers-including cervical carcinoma-over-express hTERT, the catalytic domain of the telomerase complex. Only a limited set of viruses within the Alphapapillomavirus genus are oncogenic. The viral functions responsible for this distinction are not well understood. The human papillomavirus type 16 E6 protein activates the hTERT promoter. We used a luciferase-based assay to test the ability of 29 viral types, representing all current species within the Alphapapillomavirus genus, to activate the hTERT promoter. We show that oncogenic types specifically activate the hTERT promoter, while non-oncogenic types do not. Statistical analysis supports the notion that activation of the hTERT promoter is uniquely associated with oncogenic types, independent of evolutionary relationships. This finding begins to shed light on the viral phenotypes correlated with oncogenic potential.