General introduction and thesis outline 13 1 of the cervix on the vaginal side), which is lined with multi-layered squamous epithelium and the endocervix (the inner part of the cervical canal on the uterine side), which is covered with single layered glandular epithelium. The squamocolumnar junction (SCJ) is where these two types of epithelia meet. Hormonal changes induce the replacement of a portion of the endocervical columnar epithelium by squamous metaplastic epithelium and is regulated by oestrogen levels. Over time, the location of the SCJ gradually shifts. During birth, the SCJ is found at the external os, while during puberty, the SCJ moves further up the endocervical canal towards the internal os. Postmenopausal the SJC moves back down the endocervical canal. The dynamic and macroscopically visible region between the former and new SCJ is called the transformation zone (TZ). Different types of stem cells maintain the epithelial layers of the cervix. The squamous epithelium of the ectocervix is maintained by ‘conventional’ stem-like cells in the basal epithelial layer 6. The cells in the transformation zone and endocervix are maintained and Increasing epithelial differentiation Ectocervix Endocervical gland Reserve cell Superficial layers Suprabasal layers Parabasal layer Basal layer Basement membrane Epithelial stem or stem-like cell SCJ Endocervix Transformation zone Infectious virion Cervix Cuboidal cell Figure 1.2 Schematic representation of the anatomy of the uterine cervix with detailed illustration of the cervical transformation zone and the squamocolumnar junction. Cervical cancer usually arises from the cervical transformation zone, a region of the cervix where endocervical columnar epithelial cells are replaced by squamous metaplastic cells. Specific epithelial stem cells (reserve and cuboidal cells) are thought to be particularly vulnerable to HPV-associated neoplastic transformation, and infection of these cells is thought to initiate cervical carcinogenesis. Adapted from Schiffman et al., Nat Dis Prim, 2016 5. Abbreviations: SCJ, squamocolumnar junction
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