Fig. 1.

HPV+ cancer cell metabolic scheme. Activation of mTOR upregulates numerous proteins involved in cellular metabolism, which together in a cancer cell promote the Warburg effect and excessive lactate production. The HPV-16 E6 oncoprotein has been implicated in activating mTOR, though the specific mechanism remains undefined. Not depicted, the E7 oncoprotein has also been described to contribute to this highly glycolytic phenotype by blocking entrance into the TCA cycle through inhibition of the terminal glycolytic enzyme, pyruvate kinase, specifically the embryonic M2 splice variant (PK-M2) which reemerges as the dominant isoform in many cancers.¹⁵