Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 and pRb pathways, and to prosenescent mTOR signaling. Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6/E7 but evade senescence through hypoxia-induced mTOR impairment. Prospective E6/E7 inhibitors may therefore benefit from a combination with treatment strategies directed against hypoxic tumor cells.

预计人类乳头瘤病毒（HPV）诱发的癌症将在数十年内仍然是全球范围内的主要健康问题。HPV阳性癌细胞的生长取决于病毒E6和E7的持续表达与尚不明确的细胞改变协同作用的致癌基因。E6 / E7构成有吸引力的治疗靶标，因为对E6 / E7的抑制作用会迅速诱导HPV阳性癌细胞的衰老。这种细胞反应与抗增殖p53和pRb途径的重建以及衰老的mTOR信号传导有关。缺氧的HPV阳性癌细胞可能成为靶向E6 / E7的治疗策略的主要障碍，因为它们会下调E6 / E7但通过缺氧诱导的mTOR损伤而逃避衰老。因此，预期的E6 / E7抑制剂可能会受益于针对缺氧肿瘤细胞的治疗策略。