Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Pathog Dis. 2019 Jul 1;77(5). doi: 10.1093/femspd/ftz048.
Human papillomavirus (HPV) associated cancers, and in particular cervical cancer, are considered to be directly stimulated by HPV oncogenes. Alternatively, these types of cancers could also be indirectly stimulated by HPV-induced chronic inflammations, which in turn are also caused by HPV oncogenes activity. Chronic inflammation is associated with repeated tissue injury and development of mutations in the vital tumor suppressor genes. Thus, it is important to understand that the persistent HPV infection and its associated chronic inflammation is responsible for the progression of HPV-induced cancers. HPV E5, E6 and E7 could upregulate the expression of cyclooxygenase (COX)-2 and prostaglandin (PG) E2 followed by the activation of the COX-PG pathway. This pathway is assumed to be the main cause of HPV-induced inflammation. Additionally, HPV oncogenes could have an impact on the upregulation of pro-inflammatory cytokines in HPV-positive patients. The upregulation of such cytokines accelerates the incidence of inflammation following HPV infection. Other factors such as microRNAs, which are involved in the inflammation pathways and aging, give rise to the increased level of pro-inflammatory cytokines and could also be responsible for the acceleration of HPV-induced inflammation and consequent cervical cancer. In this review, the exact roles of HPV oncogenes in the occurrence of inflammation in cervical tissue, and the effects of other factors in this event are evaluated.
人乳头瘤病毒（HPV）相关癌症，特别是宫颈癌，被认为是由 HPV 致癌基因直接刺激的。或者，这些类型的癌症也可以间接受到 HPV 引起的慢性炎症的刺激，而慢性炎症也是由 HPV 致癌基因的活性引起的。慢性炎症与反复的组织损伤和重要肿瘤抑制基因的突变发展有关。因此，重要的是要了解持续性 HPV 感染及其相关的慢性炎症是导致 HPV 诱导癌症进展的原因。HPV E5、E6 和 E7 可以上调环氧化酶（COX）-2 和前列腺素（PG）E2 的表达，从而激活 COX-PG 途径。该途径被认为是 HPV 诱导炎症的主要原因。此外，HPV 致癌基因可能会影响 HPV 阳性患者中促炎细胞因子的上调。这些细胞因子的上调加速了 HPV 感染后的炎症发生。其他因素，如参与炎症途径和衰老的 microRNAs，导致促炎细胞因子水平升高，也可能导致 HPV 诱导的炎症和随后的宫颈癌加速。在这篇综述中，评估了 HPV 致癌基因在宫颈组织炎症发生中的确切作用，以及其他因素在这一事件中的作用。
