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.

Epidemiology of cervical cancer

Cervical cancer occurs almost exclusively in women who are or have been sexually active. There is strong molecular biological and epidemiological evidence that the predominant cause of cervical cancer is sexually transmitted human papilloma virus (HPV). There are four HPV types that are considered to be high risk (16, 18, 45 and 56), a further 11 types that are intermediate risk (31, 33, 35, 39, 51, 52, 55, 58, 59, 66 and 68) and eight that are low risk (6, 11, 26, 42, 44, 54, 70 and 73) By the age of 35, 60% of sexually active women have acquired HPV infection of the genital tract (including the vulva). This proportion is higher if the woman or her partner has had several sexual partners. In most cases the infection is symptomless and disappears within a few months (see p. 258).

Possible cofactors in cervical carcinogenesis include cigarette smoking, immunosuppression, hormonal factors and vitamin deficiencies. Prophylactic vaccination is now available either as a bivalent against the high risk HPV 16 and 18 or as the quadravalent HPV 16, 18, and the lower risk 6 and 11. A number of countries offer the vaccination from age 12–13 up to 27 years; consideration is also being given to offering the vaccine to young men before they become sexually active.

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.