Schichl Konstanze, Doorbar John
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Viruses. 2025 Jun 30;17(7):937. doi: 10.3390/v17070937.
Cervical cancer remains a global health burden, with persistent infection by high-risk human papillomaviruses (HR-HPVs) being the primary etiological factor. HR-HPVs target stem-like cells of the cervical epithelium to establish chronic infections. Upon infection of the cervical transformation zone (TZ)-a region adjacent to the squamocolumnar junction (SCJ)-these viruses drive neoplastic transformation, which is due in part to the unique cellular composition and hormonal responsiveness of the TZ. Reserve cells, which can accumulate at the cervical crypt entrances of the TZ, are thought to be highly susceptible to HR-HPV infection because of their location beneath a single layer of columnar cells. Infection of the stratified ectocervical epithelium, in contrast, requires a wound to allow basal cell infection, replication, and the expression of early genes to adjust epithelial homeostasis while facilitating immune evasion. Persistent infection by HR-HPV types, particularly HPV16 and HPV18, can result in the deregulated expression of viral genes E6 and E7, driving cell cycle disruption, genomic instability, and subsequent viral genome integration. Differences in the microenvironment and transcriptional environment of the ectocervix compared with the TZ could explain the frequent deregulation of E6 and E7 at the latter site, which can drive disease progression towards cancer.
宫颈癌仍然是一项全球卫生负担，高危型人乳头瘤病毒（HR-HPV）的持续感染是主要病因。HR-HPV靶向子宫颈上皮的干细胞样细胞以建立慢性感染。在子宫颈转化区（TZ）——一个与鳞柱交界（SCJ）相邻的区域——感染后，这些病毒会引发肿瘤转化，部分原因是TZ独特的细胞组成和激素反应性。储备细胞可聚集在TZ的子宫颈隐窝入口处，由于它们位于单层柱状细胞之下，被认为极易受到HR-HPV感染。相比之下，复层的子宫颈外上皮感染需要有伤口，以使基底细胞受到感染、复制，并表达早期基因来调节上皮内环境稳定，同时促进免疫逃逸。HR-HPV型别，特别是HPV16和HPV18的持续感染，可导致病毒基因E6和E7的表达失调，从而导致细胞周期紊乱、基因组不稳定以及随后的病毒基因组整合。与TZ相比，子宫颈外的微环境和转录环境的差异可以解释E6和E7在后者部位频繁的表达失调，这可推动疾病向癌症发展。
