The SCJ rarely remains restricted to the external os. Instead, it is a dynamic point that changes in response to puberty, pregnancy, menopause, and hormonal stimulation (Fig. 19.4). In neonates, the SCJ is located on the exocervix. At menarche, the production of estrogen causes the vaginal epithelium to fill with glycogen. Lactobacilli act on the glycogen to lower the pH, stimulating the subcolumnar reserve cells to undergo metaplasia (5).
Metaplasia advances from the original SCJ inward, toward the external os and over the columnar villi. This process establishes an area called the transformation zone. The transformation zone extends from the original SCJ to the physiologically active SCJ, as
Figure 19.2 The cervix and the transformation zone.
CHAPTER 19 Intraepithelial Disease of the Cervix, Vagina, and Vulva
Figure 19.3 Diagram of the cervix and the endocervix.
demarcated by the squamocolumnar junction. As the metaplastic epithelium in the transformation zone matures, it begins to produce glycogen and eventually resembles the original squamous epithelium, both colposcopically and histologically (Fig. 19.5A and B).
In most cases, CIN is believed to originate as a single focus in the transformation zone at the advancing SCJ. The anterior lip of the cervix is twice as likely to develop CIN as the posterior lip, and CIN rarely originates in the lateral angles. Once CIN occurs, it can progress horizontally to involve the entire transformation zone, but it usually does not replace the original squamous epithelium. This progression usually results in CIN with a sharp external border. Proximally, CIN involves the cervical clefts, and this area tends to have the most severe CIN lesions. The extent of involvement of these cervical glands has significant therapeutic implications because the entire gland must be destroyed to ensure elimination of the CIN (5). The only way to determine where the original SCJ was located is to look for nabothian cysts or cervical cleft openings, which indicate the presence of columnar epithelium. After the metaplastic epithelium matures and forms glycogen, it is called the healed transformation zone and is relatively resistant to oncogenic stimuli. The entire SCJ with early metaplastic cells is susceptible to oncogenic factors, which may cause these cells to transform into CIN. Therefore, CIN is most likely to begin either during menarche or after pregnancy, when metaplasia is most active. Conversely, after menopause a woman undergoes little metaplasia and is at a lower risk of developing CIN from de novo human papillomavirus (HPV) infection. Oncogenic factors are introduced through sexual contact in general and intercourse in particular. Although several agents, including sperm, seminal ﬂuid histones, trichomonas, chlamydia, and herpes simplex virus, were studied, it is established that persistent high-risk oncogenic HPV infection is the overwhelming risk factor for the development of CIN.
Normal Transformation The original squamous epithelium of the vagina and exocervix has four layers (5): Zone 1.
The basal layer is a single row of immature cells with large nuclei and a small amount of cytoplasm.
2.
The parabasal layer includes two to four rows of immature cells that have normal mitotic figures and provide the replacement cells for the overlying epithelium.
3.
The intermediate layer includes four to six rows of cells with larger amounts of cytoplasm in a polyhedral shape separated by an intercellular space. Intercellular bridges, where differentiation of glycogen production occurs, can be identified with light microscopy.
4.