Case 10 A 29-year-old woman with an abnormal smear test

 Case 10 A 29-year-old woman with an

abnormal smear test

Christie Thomson is 29-year-old housewife. She is currently

on maternity leave after the birth of her son Caleb 4 months

ago. She had a normal delivery and initially breast fed but

has changed to bottle feeding in the last 2 weeks. Her

smear test was due 10 months previously but she postponed

this as she was pregnant. She was well during her

pregnancy and since delivery. She has not yet had a period.

She was reminded to make an appointment for a smear

at her postnatal check and attended 3 weeks ago. The

practice nurse said that her cervix looked normal so she was

shocked when she received a letter to say that she had an

abnormal smear result and that she would be sent an

appointment to attend the colposcopy clinic at her local

hospital. She has been worrying ever since and thinks that

she may have cancer. Her maternal grandmother died from

cervical cancer at age 48 and she knows her mother, who

was a teenager at the time, found this difficult to cope with;

she commented when Caleb was born how happy she was

to have a grandson. Her mother urges her to find out when

she will receive an appointment.

What should she do next?

The smear taker has the responsibility of informing

women at the time they attend for screening of:

• The purpose of cervical screening

• The likelihood of an abnormal result

• What will happen if the result is abnormal

Women are often very anxious when they receive an

abnormal smear result. Some women confuse cervical

screening with a test for cancer (Box 10.1 ). If her local

practice has not contacted her, she should get in touch

to discuss her result. This may be by telephone.

Christie phones her practice and speaks on the telephone to

the practice nurse who took her smear. She reassures

Christie that the smear test shows only a mild abnormality

and in other areas, she would be invited for a repeat smear

in 6 months time as this may resolve spontaneously.

However, local practice is to refer to colposcopy to look for

precancerous changes. She is told that she should make an

appointment for about 8 weeks’ time.

Christie is very anxious about the delay. She is concerned

that her smear was not taken when it had been due during

her pregnancy and that her grandmother died from cervical

cancer.

Obstetrics and Gynaecology: Clinical Cases Uncovered.

By M. Cruickshank and A. Shetty. Published 2009 by Blackwell

Publishing. ISBN 978-1-4051-8671-1.

KEY POINT

It is safe and recommended practice to defer smears

during pregnancy. The effects of pregnancy can make it

more difficult to obtain an adequate specimen for cytology

and woman often prefer to wait.

Christie receives an appointment for the colposcopy clinic

and an information leaflet explaining what will happen at

this appointment. She is confused about the grades of

smear results and what this means for her.

What does Christie need to know about

her smear result?

Different grades of dyskaryosis are associated with

different levels of risk for underlying high grade cervical

intraepithelial neoplasia (CIN) (Boxes 10.2 and 10.3 ).

Borderline nuclear abnormalities (BNA) show no definite dyskaryosis and often regress. A repeat smear in 6

months is usually recommended. Women are referred

for colposcopy if they have three consecutive borderline

smears. Only 10% of women with persistent BNA smears

will have underlying CIN.80 Part 2: Cases

PART 2: CASES

Box 10.1 Human papillomavirus and natural

history of cervical disease

As cervical cancer is caused by an oncogenic virus, human

papillomavirus (HPV), it is not a familial cancer. There are

over 100 different genotypes of HPV.

High risk HPV types (HPV 16 and 18) are oncogenic

viruses. HPV DNA has been found in 99.7% cases of

squamous cell cancer of the cervix. Remember HPV

infection is common, with a lifetime incidence of 70–80%.

Women tend to acquire HPV infections around the time

they start having intercourse. In most instances, HPV

infection is transient; the woman’s immune system

effectively clears the virus and it has no clinical

significance. Low grade cytological changes are often

related to HPV infection (a small proportion being high risk

types) rather than cervical intraepithelial neoplasia (CIN). In

a small proportion of women, persistent HPV infection, in

particular with high risk types, results in the development

of high grade CIN (CIN 2 or 3). High grade CIN is

premalignant in that, in a proportion cases, invasive cancer

will develop in the subsequent 10–20 years. Low grade

CIN (CIN 1), however, often resolves spontaneously. High

grade CIN may not have a preceding low grade disease

but both are HPV-related.

The NHS in the UK provides an HPV vaccination for girls

aged 12–13 years against HPV 16 and 18.

Box 10.2 Dyskaryosis

This is a cytological term used to describe the nuclear

changes in exfoliated cells picked up on the smear test.

These include nuclear enlargement and irregularity in

shape and outline of the nucleus. The grade of dyskaryosis

is determined by the severity of these changes and also

the increase in ratio of nuclear size to cytoplasm which is

a reflection of the degree of loss of maturation of the cell;

the higher the ratio the more severe the degree of

dyskaryosis. The degree of dyskaryosis is not always

reflected the degree of CIN in the underlying epithelium

(Plates 10.1 and 10.2).

Box 10.3 Cervical intraepithelial neoplasia

This is a histopathological term used to describe abnormal

proliferation (dysplasia) of the squamous epithelium of the

transformation zone of the cervix.

The grade of CIN relates to the proportion (in terms of

thirds) of the epithelial thickness which has become

dysplastic. Therefore, in CIN 3 there are full-thickness

changes involving 3/3 of the epithelium. These changes

are limited to the epithelium with the basement

membrane intact. If the basement membrane is breached,

this is invasive disease (cancer) (Plate 10.3).

Christie ’ s smear has shown mild dyskaryosis. In about

20%, there will be CIN 2/3 on colposcopy and biopsy.

There are conflicting ideas on the management of low

grade abnormal smears. Currently, some centres see

women for colposcopy after a single mildly dyskaryotic

smear to speed up the diagnosis of those with CIN.

However, it is acceptable to repeat the smear in 6 months.

Those women who still have an abnormal smear are then

sent for colposcopy. This allows some women to avoid

unnecessary investigation.

Moderate or severe dyskaryosis (present in around

1.5% of smears) is associated with a 65 – 95% risk of

having high grade CIN. This needs treatment to prevent

progression to invasive cancer so surveillance is not

offered (except during pregnancy).

What information should you elicit from

Christie at the colposcopy clinic?

The aim of cervical screening is to reduce the risk of

dying from cervical cancer by detecting and treating CIN.

CIN is asymptomatic but it is common practice to

ask specifically about symptoms associated with cervical

cancer. These are intermenstrual bleeding, postcoital

bleeding, postmenopausal bleeding and abnormal vaginal

discharge.

You need to check the date of her last menstual period

(LMP) and her method of contraception as biopsy and

treatment should be avoided during pregnancy.

Remember, it is important to check that Christie

understands the reason for her referral and what to

expect at this visit.

Christie had some pink and brown discharge for 2–3 weeks

after Caleb’s birth but no bleeding since. She is not using

contraception but has not yet had sex as she is too tired.

What would you look for

on examination?

A speculum is inserted to view the cervix. Colposcopy

allows magnification and good illumination of the cervix.

The whole of the transformation zone needs to be

identified. Initial examination allows the colposcopist to

exclude any obvious signs of cancer. A weak acetic acid

solution (3 – 5%) is applied directly to the cervix. ThisCase 10 81

PART 2: CASES

highlights areas of abnormality which turn white (acetowhitening) and capillary blood vessel patterns may be

seen with high grade CIN. Acetowhitening can also be

associated with active metaplasia of the transformation

zone or human papillomavirus (HPV) infection. Following this, Lugol ’ s iodine (aqueous iodine) can be applied.

Normal squamous epithelium will stain brown (as it contains glycogen) but is not taken up by areas of CIN.

Christie’s cervix looks normal (as she was told when her

smear was taken) but CIN cannot be identified yet. On

colposcopy, the whole of her transformation zone can be

seen clearly. After applying 5% acetic acid, dense whitening

of the epithelium with an obvious mosaic pattern of capillary

vessels is seen (Plate 10.4). There are no bizarre or abnormal

vessels which would suggest invasive disease. These findings

are in keeping with CIN 3.

Can you now make a diagnosis?

Colposcopy will identify any area of abnormality.

However, the histological diagnosis on biopsy is the

gold standard for diagnosing cervical disease. Diagnostic

biopsies are usually small punch biopsies (1 – 3 mm) and

colposcopy allows the biopsy to be taken from the most

abnormal area. Excisional forms of treatment (large loop

excision of transformation zone [LLETZ]) also produce

a specimen for histology.

What should you do next?

As Christie ’ s initial referral smear was mild, there is a risk

of treating unnecessarily if you treat her at this visit

by LLETZ. She needs to have diagnostic punch biopsies

taken to confirm the diagnosis.

The report from the pathology laboratory confirms the

diagnosis of CIN 3 from her punch biopsies. Three weeks

later, Christie receives a letter from the colposcopy clinic to

advise her that her biopsies have confirmed precancerous

cells (CIN) along with information regarding her treatment

visit. She phones the clinic the make an appointment for

treatment.

Treatment

Cervical treatments preserve reproductive function. This

is important, as CIN is most prevalent in women age

aged 27 – 33 years. Ablative or destructive treatments

(cold coagulation, diathermy and laser ablation) destroy

the transformation zone so a histological diagnosis is

essential to confirm the presence of CIN and to exclude

cancer before treatment. LLETZ is the most common

mode of treatment. This procedure allows excision of the

abnormal transformation zone using a diathermy loop

and is usually performed under local anaesthetic in the

outpatient clinic. Short - term side - effects are uncommon

and include bleeding and infection. Cone biopsy is less

common but it is an acceptable form of conservative

treatment for microinvasive cancer (FIGO Stage 1a1).

On review, Christie has mild dyskaryosis identified as

part of the national cervical screening programme. This

was investigated by colposcopy and a diagnostic biopsy

was taken targeted at the most abnormal area on colposcopy. Histology confirmed high grade CIN. High grade

CIN is treated to avoid progression to invasive cancer

over a 10 – 20 year period. As there is no evidence of

invasive disease on her colposcopy examination or on

punch biopsy, she can be safely treated using an ablative

or excisional treatment.

Christie is relieved to be offered treatment promptly. She

has a LLETZ procedure with a paracervical block using local

anaesthetic and adrenaline to reduce bleeding. Following

treatment, she had some period-like cramps for a day and

some light vaginal bleeding for 3 weeks. She was advised to

attend the colposcopy clinic in 6 months for a follow-up

smear.

Follow-up

Follow - up following conservative treatment of CIN is

important in the detection and early treatment of treatment failure or the development of recurrent CIN.

Women who have been treated for high grade CIN have

a relative risk for cervical cancer which is eight times

greater than the general population. Follow - up with cervical smears is recommended after the treatment of high

grade CIN (CIN 2/3) for 10 years in England and Wales

and 5 years in Scotland. For low grade (CIN 1), annual

follow - up is for 2 years across the UK. Colposcopy may

be performed at the first follow - up visit 6 months after

treatment but this is not essential. Once follow - up is

completed women return to routine 3 - yearly recall. Currently, there are HPV sentinel sites in England which use

HPV testing to reduce the duration of follow - up.82 Part 2: Cases

PART 2: CASES

CASE REVIEW

The cervical screening programmes in the UK have successfully reduced the incidence and mortality from cervical

cancer. Women are identified and called for screening on

the basis of age although the criteria vary across the UK.

Mild dyskaryosis accounts for around 2% of all smear

results and in a proportion of cases it is associated with

high grade CIN. Colposcopy is used to illuminate and

magnify the cervix to inspect the cervical epithelium and

identify any areas suggestive of CIN and to exclude any

obvious changes indicative of cancer.

Low grade CIN can be managed conservatively but can

be treated in the same way as high grade CIN if it persists,

if the patient requests treatment or if the woman has completed her family. Treatment of high grade CIN can be

treated using ablative or excisional methods but the treatment success rate of around 95% is the same for all treatment modalities.

Women treated for CIN remain at an increased risk of

developing cervical cancer compared to the general population so follow - up by cytology (or HPV testing in selected

sites) is essential.

The impact of the HPV 16/18 vaccination programme

for girls at age 12 years will take a number of years to be

seen given the long natural history of HPV infection and

the development of CIN and cancer.

KEY POINTS

• Cervical smear screening is aimed at detecting cytological

abnormalities (dyskaryosis)

• Organized screening programmes have successfully

reduced the incidence of cervical cancer

• The cervical sample taken uses a plastic broom sampling

device and it is collected in liquid-based cytology medium.

Although no longer a ‘smear’, may people still refer to

cervical cytology samples as ‘smear’ tests

• Women are often very anxious on receiving an abnormal

smear result or attending for colposcopy. It is essential to

provide adequate information and support

• The investigation of these changes at colposcopy may

identify premalignant disease (CIN)

• CIN is asymptomatic

• The diagnosis is made by histology of biopsies or

treatment specimens

• This allows early treatment at its premalignant stage and

prevention of deaths from cancer

• Treatment is usually LLETZ but ablative methods are also

used

• Women should be appropriately counselled about the

results of the smear and encouraged to attend follow-up

investigation and long-term cytology follow-up

Further reading

NHS CSP document 20 . Programme management. Sheffield,

2003 .