THE CERVIX (FIG. 1.1)
The cervix is the lower fibromuscular portion of the uterus. It is cylindrical or conical in shape measuring 3 to 4 cm in length, and 2.5 cm in diameter. It is supported by the cardinal and uterosacral ligaments, which stretch between the lateral and posterior portions of the cervix and the walls of the bony pelvis. The portion of cervix exposed to vagina is exocervix or portiovaginalis, which is rendered for colposcopic examination directly. The cervix varies in size and shape depending on the woman's age, parity and hormonal status. In parous women, it is bulky and the external os appears as a wide, gaping, transverse slit whereas in nulliparous women, the external os resembles a small circular opening in the centre of the cervix.
The external os opens into the endocervical canal, which is approximately 2 to 3 cm in length and opens proximally into endometrial cavity at the internal os. Endocervical canal can be visualised on colposcopy with the help of endocervical speculum specially designed for this purpose.
The part between the cervix and the lateral vaginal walls is the lateral fornix; and that between the anterior and posterior walls of the vagina and the cervix are termed the anterior and posterior fornix, respectively.
The stroma of the cervix is composed of dense, fibromuscular tissue through which vascular, lymphatic and nerve supplies to the cervix pass and form a complex plexus.
The arterial supply of the cervix is derived from internal iliac arteries through the cervical and vaginal branches of the uterine arteries.
The veins of the cervix run parallel to the arteries and drain into the hypogastric venous plexus.
The lymphatic vessels from the cervix drain into the common, external and internal iliac nodes, obturator and the parametrial nodes.
The nerve supply to the cervix is derived from the hypogastric plexus.
The endocervix has extensive sensory nerve endings, while there are very few in the ectocervix. Hence, procedures such as 3biopsy, electrocoagulation and cryotherapy are well tolerated in most women without local anaesthesia. Since sympathetic and parasympathetic fibres are abundant in the endocervix, dilatation and curettage of the endocervix may occasionally lead to a vasovagal reaction.
EPITHELIUM
Cervical mucosa generally contains both stratified squamous epithelium and columnar epithelium. Stratified squamous epithelium lines the exocervix, and continues in the fornices and vagina. The columnar epithelium is mucous secreting and characteristic of endocervical canal.
Columnar epithelium may extend from endocervix to exocervix, a condition known as ectopy.
Columnar Epithelium
It is derived from Mullerian duct.
The columnar epithelium is mucous secreting and consists of a single layer of cylindrical cells with round basal nucleus and mucous laden apical pole (Fig. 1.2).
It appears reddish in colour (the stromal vasculature can easily be seen through the thin single cell layer).
At its distal or upper limit it merges with the endometrial epithelium and proximally meets with the squamous epithelium.
It covers a variable extent of the ectocervix, depending upon the woman's age, reproductive, hormonal and menopausal status. The columnar epithelium in the cervical canal is thrown into multiple longitudinal folds protruding into the lumen of the canal, giving rise to papillary projections. It forms several invaginations into the substance of the cervical stroma, resulting in the formation of endocervical crypts/glands.
This complex architecture, consisting of mucosal folds and crypts, gives the columnar epithelium a grainy appearance on visual inspection.
Glycogenation and mitoses are absent in the columnar epithelium.
Due to lack of intracytoplasmic glycogen, the columnar epithelium does not change colour after the application of Lugol's iodine or remains slightly discoloured with a thin film of iodine solution.
In between the columnar cell layer and basement membrane small flattened cells with scarcely visible cytoplasm known as reserve cells are present, from which the mucosa regenerates. These cells play an important role in the histogenesis of dysplasia.
Cervical mucous production is under hormonal influence and varies in consistency during the different phases of menstrual cycle. It is profuse, clear and thin around the time of ovulation and helps to get clear colposcopic view. It is thick and scanty in postovulatory phase, hampering the clear colposcopic view.5
Stratified Squamous Epithelium
This is of cloacal origin, derived from endodermal portion of urogenital sinus.
It is approximately 0.5 mm thick with 15 to 20 layers of cells, is opaque pale pink in colour. This epithelium may be native to the site formed during embryonic life, which is called the native or original squamous epithelium, or it may have been newly formed as metaplastic squamous epithelium in early adult life. In premenopausal women, the original squamous epithelium is pinkish in colour, whereas the newly formed metaplastic squamous epithelium looks somewhat pinkish-white on visual examination (Fig. 1.3).
The histological architecture of the squamous epithelium of the cervix reveals, at the bottom, a single layer of round basal cells with a large dark-staining nuclei and little cytoplasm, attached to the basement membrane. The basement membrane separates the epithelium from the underlying stroma. The epithelial-stromal junction is usually straight.
Sometimes, it is slightly undulating with short projections of stroma at regular intervals called papillae and the parts of the epithelium between the papillae are called rete pegs.
The basal cells divide and mature to form the next few layers of cells. Cellular layers show increasing maturation from the base towards the surface, and characterised by increase in the cell size and reduction in the nucleus size (Table 1.1).
The maturation of the squamous epithelium of the cervix is dependent on oestrogen. If oestrogen is lacking, full maturation and glycogenation does not take place.
Hence, after menopause, the cells do not mature beyond the parabasal layer and do not accumulate as multiple layers of flat cells so the epithelium becomes thin and atrophic. On visual examination, it appears pale, with subepithelial petechial haemorrhagic spots, as it is easily prone to trauma.
SQUAMOUS METAPLASIA
The physiological replacement of the everted columnar epithelium by a newly formed squamous epithelium is called squamous metaplasia.
The vaginal environment is acidic during the reproductive years and during pregnancy and this is thought to play a role in squamous metaplasia. The irritation of exposed columnar epithelium by the acidic vaginal environment results in the appearance of subcolumnar reserve cells. These cells proliferate producing a reserve cell hyperplasia and eventually form the metaplastic squamous epithelium. These eventually lift off the persistent columnar epithelium (Fig. 1.4).
Reserve Cells
The exact origin of the reserve cells is not known, though it is widely believed that it develops from the columnar epithelium, in response to irritation by the vaginal acidity.
This is initially seen as a single layer of small, round cells with darkly staining nuclei, situated very close to the nuclei of columnar cells, which further proliferate to produce a reserve cell hyperplasia. Morphologically, the reserve cells have a similar appearance to the basal cells of the original squamous epithelium, with round nuclei and little cytoplasm. As the metaplastic process progresses, the reserve cells proliferate and differentiate to form a thin, multicellular epithelium of immature squamous cells with no evidence of stratification. The cells in the immature squamous metaplastic epithelium do not produce glycogen and, hence, do not stain brown or black with Lugol's iodine solution. Groups of mucin-containing columnar cells may be seen embedded in the immature squamous metaplastic epithelium at this stage. Squamous metaplasia usually begins at the original squamocolumnar junction at the distal limit of the ectopy, but it may also occur in the columnar epithelium close to this junction or as islands scattered in the exposed columnar epithelium. As the process continues, the immature metaplastic squamous cells differentiate into mature stratified metaplastic 9epithelium. A few residual columnar cells or vacuoles of mucus are seen in the mature squamous metaplastic epithelium, which contains glycogen from the intermediate cell layer onwards and thus stains brown or black after application of Lugol's iodine. Nabothian cysts are retention cysts that develop as a result of the occlusion of an endocervical crypt opening or outlet by the overlying metaplastic squamous (Fig. 1.5). The buried columnar epithelium continues to secrete mucus, which eventually fills and distends the cyst giving it an ivory-white to yellowish hue. New cysts containing fluids and mucous are blue in colour but dense mucous appears as ivory yellow colour. The laminated vessels between cysts and squamous epithelium are clearly visible. The columnar epithelium in the wall of the cyst is flattened and ultimately destroyed by the pressure of the mucus in it. The outlets of the crypts of columnar epithelium, not yet covered by the metaplastic epithelium, remain as persistent crypt openings (Fig. 1.6).
Fig. 1.5: Squamous metaplastic epithelium covering the crypt openings, leading to the formation of Nabothian retention cysts
The farthest extent of the metaplastic epithelium onto the ectocervix can be best judged by the location of the crypt opening farthest away from the squamocolumnar junction. Squamous metaplasia is an irreversible process; the transformed epithelium (now squamous in character) cannot revert to columnar epithelium. The metaplastic epithelium adjacent to the squamocolumnar junction is composed of immature metaplasia, and the mature metaplastic epithelium is found near the original squamocolumnar junction. Further development of the newly formed immature metaplastic epithelium may take two directions. In majority of women, it develops into a mature squamous metaplastic epithelium. In a small minority of women, an atypical, dysplastic epithelium may develop.
Certain oncogenic human papillomavirus (HPV) types may persistently infect the immature basal squamous metaplastic cells and transform them into atypical cells with nuclear and cytoplasmic abnormalities. The uncontrolled proliferation and expansion of these atypical cells may lead to the formation of an abnormal dysplastic epithelium which may regress to normal, persist as 11dysplasia or progress into invasive cancer after several years.
The metaplastic process begins at the tip of the columnar villi; which are first exposed to vaginal milieu. As this metaplasia replaces the columnar epithelium, the central capillary of villus regresses and the epithelium flattens out. This epithelium with its typical vascular network is well defined on colposcopy.
SQUAMOCOLUMNAR JUNCTION
The squamocolumnar junction appears as a sharp line with a step, due to the difference in the height of the squamous and columnar epithelium (Fig. 1.7). The location of the squamocolumnar junction in relation to the external os is variable depending upon age, hormonal status, birth trauma, oral contraceptive use and certain physiological conditions such as pregnancy.
The squamocolumnar junction visible during childhood, perimenarche, after puberty and early reproductive period is referred to as the original squamocolumnar junction, as this represents the junction between the columnar epithelium and the ‘original’ squamous epithelium laid down during embryogenesis and intrauterine life.
During childhood and perimenarche, the original squamocolumnar junction is located at, or very close to, the external os (Fig. 1.8).
After puberty and during the reproductive period, under the influence of oestrogen the cervix swells, enlarges and the endocervical canal elongates. This leads to the eversion of the columnar epithelium of the lower part of the endocervical canal on to the ectocervix. This condition is called ectropion or ectopy, which is strikingly reddish-looking ectocervix on visual inspection. Thus the original squamocolumnar junction is located on the ectocervix, far away from the external os Ectropion becomes much more pronounced during pregnancy. The buffer action of the mucus covering the columnar cells is interfered with when the everted columnar epithelium in ectropion is exposed to the acidic vaginal environment. This leads to the destruction and eventual replacement of the columnar epithelium by the newly formed metaplastic squamous epithelium. The metaplastic process mostly starts at the original squamocolumnar junction and proceeds centripetally towards the external os through the reproductive period to perimenopause. Thus, a new squamocolumnar junction is formed between the newly formed metaplastic squamous epithelium and the columnar epithelium remaining everted onto the ectocervix. It is the region in which physiological transformation to squamous metaplasia, as well as abnormal transformation in cervical carcinogenesis, occurs.13
Fig. 1.8: Location of the squamocolumnar junction (SCJ) and transformation zone; (A) before menarche; (B) after puberty and at early reproductive age; (C) in a woman in her 30s; (D) in a perimenopausal woman; (E) in a postmenopausal woman
As the woman passes from the reproductive to the perimenopausal age group, the location of the new squamocolumnar junction progressively moves on the ectocervix towards the external os.
From the perimenopausal period and after the onset of menopause, the cervix shrinks (due the lack of oestrogen) and the movement of the new squamocolumnar junction towards the external os and into the endocervical canal is accelerated. In postmenopausal women, the new squamocolumnar junction is often invisible on visual examination.
TRANSFORMATION ZONE
This is the region of the cervix where the columnar epithelium has been replaced and/or is being replaced by the new metaplastic squamous epithelium.
It corresponds to the area of cervix bound by the original squamocolumnar junction at the distal end and proximally by the new squamocolumnar junction formed after squamous metaplasia (Fig. 1.9).
In premenopausal women, the transformation zone is fully located on the ectocervix. After menopause through old age, the cervix shrinks (with the decreasing levels of oestrogen) and the transformation zone moves partially and later fully into the cervical canal.
Identifying the transformation zone is of great importance in colposcopy, as almost all manifestations of cervical carcinogenesis occur in this zone (Fig. 1.10).
The transformation zone is normal when it is composed of immature and/or mature squamous metaplasia along with intervening areas of columnar epithelium, with no signs of cervical carcinogenesis.15
It is termed an abnormal transformation zone (ATZ) when evidence of cervical carcinogenesis such as dysplastic change is observed in the transformation zone.