CERVICAL PRECANCER AND CANCER

The cervical epithelium undergoes changes throughout the menstrual cycle and is readily accessible for examination. The epithelium covering the ectocervix is stratified and identical to that of the vagina (Fig. 37.1). It is separated from the underlying stroma by an apparent basement membrane. Superior to this is a layer of basal cells from which the other cell layers differentiate. Above the basal layer are five or six layers of parabasal cells. Above these are intermediate and superficial cell layers. The intermediate cell layer consists of large cells, each with reticulated nuclei and vacuoles of glycogen in the cytoplasm. The superficial cell layer varies in thickness, depending on the oestradiol : progesterone ratio. The superficial cells are flattened and have small nuclei, the cytoplasm containing glycogen (Fig. 37.2). A small amount of keratin is produced in some of the cells, which becomes ‘cornified’. During the reproductive years the superficial cells are constantly shed or exfoliated into the vagina, and differentiation of cells from the basal layer also proceeds constantly.

Fig. 37.1 Normal squamous epithelium covering the vaginal portion of the cervix.

Fig. 37.2 Normal exfoliated cervical cells.

The characteristics of the superficial cells can be studied by taking a smear from the cervix and staining it with Papanicolaou’s stain. In some women the nuclei become abnormally shaped or dyskaryotic, which may indicate a precancerous change; this can be detected by cervical smears.

Cervical exfoliative cytology

The development of cervical carcinoma is preceded by the appearance of abnormal (dyskaryotic) cervical cells. These can be detected by microscopically examining an exfoliative cervical smear, stained using the Papanicolaou stain (the Pap test). As this is a screening test false negatives may occur, estimated at 5–15%. The proportion of false-negative smears will be reduced if strict criteria are adopted for taking and for examining the smear.

A further refinement is liquid-based cytology that involves taking cervical cells with a Cervex sampler brush and rinsing the brush into a vial of fixative. The cells are not obscured by blood or mucus and are all fixed properly. In the laboratory, a monolayer of cells is made which is easier to interpret. If the result is inconclusive, the remaining cells in the vial can be used to make a hybrid capture test, which will detect the presence of oncogenic HPV. This methodology reduces the unsatisfactory/inconclusive smear rate by 80% and has been shown to be cost-effective. A further advantage of this test is that it is likely to reduce the number of colposcopies that gynaecologists make when an inconclusive Pap smear abnormality is found. The technique has the potential to be used for the detection of other sexually transmitted diseases, such as chlamydia and gonorrhoea.

The recommended smear regimen is summarised in Box 37.1. In women aged 30 and over, the doctor or nurse taking the smear should also examine the woman’s breasts, teach her breast self-examination, and after the age of 40 measure her blood pressure.

Box 37.1 Recommended cervical screening regimens

Australia

Commence age 18–20 years or 1–2 years after first intercourse.

Repeat every 2 years until age 70 if had two normal smears in previous 5 years.

UK

Commence age 25 years (as risk of cervical cancer very low under 25 years).

Repeat every 3 years until age 50, then 5-yearly until 64 years.

Technique for taking a cervical smear

A tray is provided on which a bivalve vaginal speculum, some slides, a spray-on fixative plastic, a modified Ayre spatula and an endocervical brush are placed. Before performing a vaginal examination, the warmed speculum is inserted to expose the cervix. The cytobrush is inserted into the cervical canal and rotated. The sample is smeared on to the slide. The ectocervix is sampled with the Ayre spatula or Cervex brush by rotating it twice through 360° and the sample is smeared on to a slide (Fig. 37.3). If liquid-based cytology is being used the brush is placed in the liquid medium.

Fig. 37.3 Methods of obtaining cells from the cervix for cytological examination, using (1) a special wooden spatula, (2) an Ayre spatula, and (3) a Cervex sampler.

The smears are sent to a reliable, quality assured cytological laboratory for examination.

REPORTING ON SMEARS

Cytologists have agreed that nuclear abnormalities should form the basis of a cytological diagnosis. They have agreed to report smears as follows:

Fig. 37.4 Exfoliated cervical cells showing severe dyskaryosis.