In this study, using the largest cohort of HPVU cervical cancers reported to date, we have performed detailed biological characterization which has identified cell cycle regulation as a rational target for HPVU tumors, and, using a panel HPV+ and HPVU cell lines, we have shown that the CDK4/6 inhibitor palbociclib is a potential alternative treatment strategy. The gene discussed is CDK4; the disease is cervical carcinoma.