Human papillomavirus type 16 (HPV-16) E7 protein has previously been shown to alter the AKT signaling pathway. Here we show that HPV-16 E7-positive high-grade intraepithelial cervical lesions (HSIL, bottom panel exhibited elevated active AKT (green) when compared to normal cervical tissue. Loss of the retinoblastoma protein (Rb,red), induced by E7, correlates with elevated AKT activity (green) in HSIL tissue (bottom panel) in contrast to normal cervical epithleium (top panel). Together these data demonstrate that HPV-16 E7 can up-regulate AKT activity in cervical precancer lesions through inhibition of Rb. Mechanistically understanding how Rb regulates the PI3K-AKT pathway is of future interest and may provide new downstream effectors of Rb loss that contribute to tumor formation and cancer. For details, see the article by Menges et al. on page 5555 of this issue.