Sexual Health and Genital Medicine in Clinical Practice

Chapter 11. Cytology and Colposcopy

Cervical cancer is in most cases a preventable disease and cervical cytology is an effective method of screening for abnormalities that have the potential to progress to cancer. The current UK National Guidelines for cervical screening are as follows:

 First smear at 25 years of age

 Three yearly smears between ages 25 and 49

 Five yearly smears between ages 50 and 64

 Smears recommended above the age of 65 if a recent abnormal smear or no screening performed since the age of 50.

Sexual health issues can be usefully discussed at the time of first cytology and screening for sexually acquired infections, in particular chlamydia, considered. For this reason, some clinicians are concerned at delaying screening until 25 years of age. From a cancer prevention perspective, the delay in initiating screening is certainly cost-effective as cervical cancer below the age of 25 is rare in the UK. In 2002, five deaths from cervical cancer were registered amongst women aged between 16 and 24 years of age.

Repeating cytology every 2 years is 50% more expensive than screening every 3 years. A study from the United States has shown that in a well screened population, three yearly screening would prevent virtually all cervical cancers prevented by annual screening with an additional 70000 smears and 400 colposcopic examinations being needed to prevent one extra cancer.

Extending the screening period after the age of 50 is based on data showing that the prevalence of CIN III and cervical cancer is very low beyond this age in a well-screened population.

Cervical cytology has an approximately 70% sensitivity for detecting cervical pathology and hence there is a need for an improvement in cervical screening technology. Liquid based cytology (LBC) has now replaced conventional cytology in the USA, UK and some other European countries. A Cervex brush (or similar sampling tool) is used to obtain the cervical sample and, instead of smearing on to a microscope slide, the brush is vigorously ‘stirred' into a buffer solution to produce a suspension of cells. This is then used to produce a monolayer of cells, without the usual blood cells and other debris. These cleaner samples can be read more quickly and should increase the sensitivity for detecting pathological changes and reduce the number of inadequate samples. However, recent commentators have questioned the claims that LBC performs better than conventional cytology and have emphasised the need for large randomized controlled trails.

The use of HPV testing to improve on sensitivity and as a cost- effective means of triaging women for colposcopy is currently being studied. A positive result for one of the "high risk" HPV types (e.g. HPV 16 or 18) is known to generate patient anxiety and yet this often represents only a transient infection of no long-term consequence. Persistent infection or infection associated with dyskaryosis is of greater significance and it is likely that HPV testing will be used in conjunction with cytology as a means of identifying more accurately those women at risk of developing high grade dysplasia and cervical carcinoma. Women with persistent borderline or mildly abnormal smears and a positive result for high risk HPV types may be colposcoped earlier than if high risk HPV testing proved negative.

11.1 TAKING A SMEAR

Most of us will have passed through undergraduate training without proper instruction on how to take a cervical smear and occasionally the basic principles are forgotten, even by the most experienced clinician. There are three important points to consider:

(1) To obtain a "good" smear the cervix must be well visualized.

This is an obvious point but not always followed. The following guidelines may help to make the procedure a little easier for both patient and practitioner.

(a) Try to relax the patient.

(b) Warm the speculum.

(c) Use an appropriately sized speculum. A nulliparous woman in her early twenties usually requires a smaller speculum than a 40-year-old woman with five children. A very long speculum is occasionally required; it is well worthwhile keeping one or two in the surgery.

(d) Insert the speculum gently and open slowly looking for the cervix as you proceed. Inserting the speculum completely before opening sometimes leads to the cervix being passed and provides only a view of the anterior or posterior fornix. "Gently" is the key; a heavy hand leads to discomfort and may deter the patient from attending for gynecological examinations in the future.

(e) Good lighting is essential.

(2) Cervical dysplasia and neoplasia usually originate in the "transformation zone" adjacent to the "squamo-columnar junction" (see Figure 11.1). To help adequately sample this area a range of shapes of cervical spatulae and brushes are available (Figure 11.2). Pick the most appropriate device for the individual cervix. As a basic guide, if there is no obvious ectropion or ectopy, the squamo-columnar junction will be just at or inside the cervical os, then an Aylesbury spatula or "Cervex" sampler should provide an adequate sample. A cervical brush can also be used but ideally this should be in conjunction with a sample obtained by spatula. A "brush only" sample often contains too few squamous cells for adequate assessment. Brush and spatula samples may be spread on to different halves of the same slide. Take the brush sample last as the cells tend to dry out quickly, roll the brush over the slide and fix immediately. Combined ‘brush and spatula' samples are usually required after cervical surgery (e.g. LLETZ (large loop excision of the transformation zone), laser, cone biopsy).

Figure 11.1. Cervical ectopy demonstrating well the squamo-columnar junction

Figure 11.2. Cervical spatulae and brushes for cervical cytology (a) Aylesbury spatula (b) Ayre's spatula (c) Cervex® brush (d) Cytobrush®

An Aylesbury spatula should also be suitable if there is a small ectropion whereas an Ayre's spatula is probably best reserved for the cervix with a moderately sized or large ectropion. The entire squamo-columnar junction must be sampled which in some women requires quite firm pressure if the posterior aspect of the junction is to be reached. Two or three 360° turns usually picks up sufficient material combined with a lateral sweep if the ectropion is particularly large. Spread the material evenly over the microscope slide and fix immediately. if there is only a scanty amount of material on the slide, resample with a "Cervex" brush or one of the newer plastic/foam bendable devices, again remembering to aim for the squamo-columnar junction.

Mention on the cytology form if you have used a cervical brush because it often picks up glandular components that can give the cytologist the false impression of cervical pathology.

it is important to note that sampling is somewhat simplified with liquid based cytology, which requires the use of a Cervex brush or similar sampling tool. Cervical smears are best performed at mid-cycle but the opportunity should not be missed to take a smear at other times, except during menstruation.

(3) A large number of women think that the main objective of cervical cytology is to detect cervical cancer and there are probably an appreciable number who are deterred from having cervical smears because of this. The misconception is reinforced by using the term "cancer smear" and by telling women with negative smears that there was "no evidence of cancer/malignancy." When a subsequent smear shows "slight abnormalities" very reasonably the thought of cancer will come to mind and generate a great deal of unnecessary anxiety. Our health education message needs to change to ensure that women fully understand the purpose of cervical smears, that is to detect changes in the cells of the cervix which may, in a small number of cases, progress to cancer over many years. Greater emphasis should be made of the likelihood of minor abnormalities returning to normal and of the fact that if these minor changes persist or progress then treatment can be initiated and so prevent the development of cancer at a later date. unfortunately, because there is currently no way of determining which changes will return to normal and which will progress, a number of women undergo unnecessary treatment. Continued surveillance of minor cervical pathology by cytology and colposcopy does cause anxiety and many women therefore prefer to opt for treatment.

11.2 SMEAR REPORT:TERMINOLOGY BRIEFLY EXPLAINED

Cervical smear terminology is rather complicated and can be very difficult to explain in simple lay terms. It is well worthwhile spending a little time discussing the possible results and their significance with the patient at the time of taking the smear and providing an information leaflet to take away. This may help to reduce anxiety should the smear need repeating at an earlier time interval or should there be a need to refer on for colposcopy.

11.2.1 Inadequate Specimen

There are a number of reasons why a smear is considered inadequate for assessment and some of these may be rectified before the smear is taken or sent to the laboratory.

(1) Scanty specimen. As mentioned above, if there is little material on the slide, repeat the sampling with a Cytobrush or Cervex brush. This should be mentioned on the smear form.

(2) Blood stained specimen: too many red blood cells for adequate assessment. Some cervices bleed profusely as the smear is taken. This may indicate cervicitis or too firm a pressure when sampling. If there is some cervical mucus on the slide, it is probably worthwhile sending the specimen to the laboratory. If the smear appears to be purely blood, repeat at a later date. If bleeding occurs again then check for cervical infection, in particular Chlamydia. Consider treating with a tetracycline or alternatively refer to GU medicine for assessment.

(3) Excessive bacteria. This is usually due to bacterial vaginosis, a condition caused by an overgrowth of various bacteria, in particular Gardnerella vaginalis, Mycoplasma hominis, Bac- teroides spp., and other anaerobes (see chapter 4). If these cover the specimen, the cervical cells are obscured and therefore cannot be properly assessed. Bacterial vaginosis usually requires treatment only if there are symptoms of vaginal discharge; however, when the condition interferes with cervical cytology consider treating before resampling.

(4) Excess pus cells/polymorphs. This may result from cervicitis or vaginitis. If you think clinically there is a vaginitis, take a swab for Trichomonas and Candida culture and treat with an antifungal. If there is clinical evidence of cervicitis, and this may be very difficult to assess, check for cervical pathogens such as Chlamydia and N. gonorrhoeae. Ideally, patients with presumed cervicitis should be referred to GU medicine for assessment.

Candida may be seen on a cervical smear but it usually interferes with assessment only if there are excessive numbers of pus cells or candidal pseudohyphae and spores. Treatment is necessary only if symptoms are present or if the smear cannot be adequately assessed.

Trichomonas vaginalis may also be seen on a cervical smear; however, it is always worth confirming with vaginal culture as false positive results may occur with cytology.

(5) No endocervical component present. There is continuing debate as to whether an adequate smear needs to contain endocervical and/or metaplastic cells. In fact, the only smears that can be judged with certainty as adequate are those containing abnormal cells. The presence of endocervical/meta- plastic cells suggests that the squamo-columnar junction has been sampled, either partly or fully. If no endocervical component is present in a woman's first smear, consider repeating in 3 months. If previous smears have been negative, consider repeating in 1 year.

(6) Poor spreading of material or poor fixation. Always remember to spread the sample as evenly as possible over the slide and fix immediately before it air dries.

11.2.2 Inflammatory Smear

This is less commonly referred to nowadays; however, some cytology laboratories use this term to mean excessive pus cells suggesting inflammation and possible infection. More commonly, however, it refers to nuclear abnormalities insufficient to be termed dyskaryosis. If there is clinical evidence of cervicitis or the patient has noticed an increased discharge, either check for infection (Chlamydia and gonorrhea) in the surgery or preferably refer to GU medicine. If the cervix looks normal, repeat the smear in 3-6 months time. The inflammatory changes often resolve without antibiotic treatment. If inflammatory changes persist, check for infection as mentioned above and consider prescribing a course of tetracycline or erythromycin. If no infective cause is found and there is no improvement with antibiotics, refer for colposcopy.

11.2.3 Human Papillomavirus Infection (see also Chapter 18)

Human papillomavirus is the commonest sexually transmitted viral infection in the developed world. Although HPV causes genital warts, most HPV infection is "subclinical." Studies using extremely sensitive methods for detecting viral DNA (nucleic acid amplification test, such as polymerase chain reaction) have identified low levels of HPV in many sexually active women. This may either clear with time or persist indefinitely. Subclinical HPV infection can sometimes be diagnosed on cervical cytology by identifying cells called "koilocytes." The cells have a prominent nucleus and the cytoplasm contains a large perinuclear halo. These appearances are considered pathognomonic of HPV infection. Certain HPV types, in particular types 16 and 18, are strongly associated with high grade cervical dysplasia (cervical intraepithelial neoplasia (CIN) II/III) and neoplasia. For this reason, women with evidence of HPV on cervical cytology require careful follow-up and the usual recommendation is to repeat the smear after 6 months.

11.2.4 Borderline Nuclear Changes

This suggests nuclear abnormalities that are insufficient to be termed dyskaryosis. Borderline nuclear changes may be found in the presence of HPV infection, in association with inflammatory changes or in women with an IUCD. A borderline smear should be repeated in 6 months; if borderline changes persist, refer for colposcopy.

11.2.5 Dyskaryosis

This means that the cell nucleus is abnormal. There are three grades of dyskaryosis: mild, moderate, and severe. The equivalent histological terms are mild, moderate, and severe dysplasia or CIN I, II, and III. The concept of dyskaryosis is very difficult to explain in lay terms. The term "pre-cancer," although theoretically correct, is a little too dramatic and often causes anxiety. An "abnormality of the cells which is not cancerous but which may in a small number of women progress to cancer over many years" is rather wordy but fairly accurate and with emphasis on "not," "may," "small," and "many" tends to avoid leaving the patient with a feeling of pending doom. It can of course be difficult to achieve the right balance between causing undue anxiety and producing excessive complacency. Tailoring the wording to the individual patient is essential.

Women with smears showing moderate or severe dyskaryosis should be referred immediately for colposcopy. There is still debate as to whether women with mild dyskaryosis require immediate colposcopy or whether the smear should be repeated at 6 months and colposcopy reserved for women with persisting abnormalities. Although the evidence for immediate colposcopy is highly persuasive, such a policy would have important practical and financial implications. One must therefore be guided by local guidelines.

In the United States, smears showing evidence of HPV infection, borderline changes or mild dyskaryosis are grouped as low- grade squamous epithelial lesions (LGSIL). Moderate and severe dyskaryosis are grouped into highgrade squamous epithelial lesions (HGSIL). The term atypical squamous cells of uncertain significance (ASCUS) is used for cells considered abnormal but neither clearly reactive nor dysplastic. The above classification, known as the "Bethesda system," has generated some controversy, in particular with respect to the merging of HPV infection with mild dyskaryosis.

11.3 COLPOSCOPY

A number of studies have reported high levels of anxiety among women attending colposcopy clinics. Providing accurate information and carefully explaining how colposcopy is performed and what is likely to happen undoubtedly reduces the anxiety. Most women will be referred for colposcopy if mild cytological abnormalities persist (e.g. borderline changes or mild dyskaryosis) or if there is a single smear showing moderate or severe dyskaryosis. The following points should be covered at the time of referral.

(1) Explain that the colposcope is purely a magnifying system that enables the cervix to be examined in greater detail. It is worth emphasizing that the colposcope does not enter the vagina and the procedure is rather like having a cervical smear. A weak vinegar solution (usually 5% acetic acid) is used to help show up abnormal areas on the cervix and this does very occasionally sting a little.

(2) If an abnormality is seen, a biopsy will be taken, usually without local anesthesia. Some women feel a short sharp pain as the biopsy is taken while others find this only mildly uncomfortable, likening the sensation to a firm pinch. A few colposcopists inject a small amount of local anesthetic prior to biopsy. This is very slightly uncomfortable but does ensure that the rest of the procedure is virtually painless.

(3) After a biopsy has been taken some women experience period-like pains that may persist for several hours. This is usually relieved by paracetamol or ibuprofen.

(4) There may be spotting of blood for a couple of days after taking a biopsy. Sexual intercourse should be avoided for a few days until healing occurs.

(5) The patient is usually asked to return in a couple of weeks for the result of histology and further management is discussed at that time. Some colposcopists prefer to "see and treat" on the first clinic attendance which usually involves performing a LLETZ.

(6) Most colposcopy clinics provide information leaflets for patients, which are sent out with the appointment. Providing information in the GP surgery at the time of referral is probably more appropriate and is best approached by having your local colposcopy clinic send details of their current management policy.

In the UK, colposcopy is recommended for the following groups:

 Three consecutive inadequate smears

 Three consecutive smears showing borderline nuclear changes in squamous cells

 One smear showing borderline nuclear changes in endocervical (glandular) cells

 Three smears reported as abnormal at any grade over a 10-year period

 Two consecutive smears showing mild dyskaryosis

 One smear showing moderate or severe dyskaryosis

11.3.1 Treatment of Cervical Intraepithelial Neoplasia

Although this will vary from unit to unit, LLETZ is the usual method used for treating CIN. This is usually performed under local anesthesia and has been shown to be a safe and effective procedure with no subsequent effect on menstruation or fertility. Repeat colposcopy is usually recommended 1 year after treatment and annual smears for 5 years.


If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!