Effects of Metformin on the virus/host cell crosstalk in human papillomavirus‐positive cancer cells

Oncogenic types of human papillomaviruses (HPVs) are major carcinogens. The viral E6/E7 oncogenes maintain the malignant growth HPV-positive cancer cells. Targeted inhibition results in efficient induction cellular senescence, which could be exploited for therapeutic purposes. Here we show that expression is strongly downregulated by Metformin cervical and head neck cells, both at transcript protein level. Metformin-induced repression glucose PI3K-dependent but—other than under hypoxia—AKT-independent. Proteome analyses reveal HPV oncogene linked to downregulation factors associated with biopsies. Notably, despite repression, induces only a reversible proliferative stop cells enables them evade senescence. also efficiently blocks senescence response targeted RNA interference. Moreover, treatment escape from chemotherapy-induced These findings uncover profound effects on virus/host cell interactions phenotype implications therapy-induced attempts repurpose as an anticancer agent development E6/E7-inhibitory strategies.