What is a Pap smear test - cervical smear test?

The History of Pap Smear tests

In 1941, George Papanicolou identified cancer cells from the fluid aspirated from the upper vagina. The test has been modified to a PAP smear test (cervical smear) taken test under direct vision from the cervix (Figure 21.5). It was shown that malignant cells could be seen in the PAP test (cervical smear) test before the cervix became malignant, indicating that screening could lead to treatment and prevention (Figure 21.6).

Figure 21.5 Cervical Speculum

Figure 21.6 Falling Mortality Rates with Cervical Screening and Treatment

Cervical cancer affects approximately 2,800 women in the UK each year, of whom roughly 1,000 die. The NHS screening programme was set up in 1988; since then, women have been invited for cervical screening at least once every five years between the ages of 20 and 64 in England and Wales and every three years between the ages of 20 and 60 in Scotland.

Cervical cancer is unusual in having a pre-invasive stage (cervical intraepithelial neoplasia, or CIN), which potentially makes it almost completely preventable by screening. In the UK, about 200,000 women each year have an abnormal cervical smear. Between 1987 and 1997, the mortality rate dropped by about 40 per cent; incidence has also fallen, from 16 women per 100,000 in 1986 to 9.6 per 100,000 in 2000. A recent paper estimated that screening saves about 4,500 lives every year.

Through What Age Range Should women have smear tests?

All women between the ages of 25 and 64 are eligible for a free cervical screening test every three to five years. In the light of evidence published in 2003 the NHS Cervical Screening Programme now offers screening at different intervals depending on age. This means that women are provided with a more targeted and effective screening programme. (http://www.cancerscreening.nhs.uk/cervical/)

The new intervals are:

Age group (years)	Frequency of screening
25	First invitation
25 - 49	3 yearly
50 - 64	5 yearly
65+	Only screen those who have not been screened since age 50 or have had recent abnormal tests

Women who have not had a recent test may be offered one when they attend their GP or family planning clinic on another matter. Women should receive their first invitation for routine screening at 25.

Evidence from Holland⁰⁹⁰¹ demonstrates that despite negative smears at the age of 50, smears should continue at least until the age of 65.

Cervical cancer is rare in women under 20. Teenagers' bodies, particularly the cervix, are still developing, which means young women may get an abnormal result when there is nothing wrong. This could lead to unnecessary treatment so screening young women might do more harm than good.

Under the age of 25 years, invasive cancer is extremely rare, but changes in the cervix are common. Although lesions treated in very young women may prevent cancers from developing many years later, the evidence suggests that screening could start at age 25. Lesions that are destined to progress will still be screen-detectable and those that would regress will no longer be a source of anxiety. Younger women will not have to undergo unnecessary investigations and treatments.

My PAP smear test (cervical smear) shows inflammation. Should I be worried?

There is no need for anxiety. Your doctor will probably wish to treat the inflammation and repeat the smear test for you. If your smear tests keep showing inflammation, referral for colposcopy (13) may be appropriate.

Inflammatory smears in cervicovaginal cytology. A finding meaning infection? (1997-01)

What are cells and what Are abnormal (pre-malignant) cells?

The body is made up largely of tiny “bricks" called cells. Each cell has a control centre called the nucleus (Figure 21.2). Malignant cells show several changes including enlargement of the nucleus and greater variation in the shapes of the nuclei and the cell (Figure 21.7). Pre-malignant cells may show similar changes. Fortunately, these changes occur before the abnormal cells descend into the deeper tissues.

Picture of normal squamous cells from the cervix. Note the small and regular cell nuclei - dark spots.

Picture of abnormal - pre-malignant cells of the cervix. note the larger and irregular cell nuclei.

The abnormal glandular smear: Cytologic prediction, colposcopic correlation and clinical management (2000)

My PAP test (cervical smear) shows abnormal cells. Does this mean that I have cancer?

Almost certainly not, although, no doubt, this is the anxiety that any woman has on learning that her smear shows an abnormality. Abnormal cells on a smear test usually mean that there may be pre-malignant changes. It is unusual for an abnormal smear to indicate that the cervix has already become malignant. These days pre-malignant conditions of the cervix can be treated before malignancy occurs.

Women's understanding of abnormal PAP test (cervical smear) test. A qualitative interview study (1997)

What are pre-malignant cells, dyskaryosis, dysplasia and CIN?

Fortunately, the cells of the cervix are not normal one day and malignant the next. It probably takes fifteen or more years before a normal cervix gradually becomes malignant. Not all pre-malignant changes progress to cancer: sometimes spontaneous return to normality may occur. Cells scraped from the cervix (PAP test (cervical smear)) can be analysed under the microscope and pre-malignant changes can be recognised. An estimate of the severity of change is generally reported (mild, moderate or severe dyskaryosis or dysplasia). These are the terms used in cytology, the study of cell structure, as a smear is sent for cytological assessment.

When the cytology indicates pre-malignancy of the cervix (Figure 21.7), a magnified assessment of the cervix (colposcopy Figure 21.8) may indicate where the abnormality is located (Figure 21.9) and a biopsy of the cervix may be obtained. The biopsies are sent for histological examination (high powered magnification of tissue;Figure 21.10). The cytological abnormalities mild, moderate and severe dyskaryosis tend to correspond to CIN I, II and III respectively (cervical intra-epithelial neoplasia (a neoplasm is a tumour). Mild, moderate and severe dysplasia are another set of histology terms for CIN I, II and III respectively). Just to complete the terminology, we sometimes call severe dysplasia (CIN III) - Carcinoma-in-situ). The important feature of pre-malignancy is that the abnormal cells are confined to the surface (epithelium).

Figure 21.8 Colposcopy

Figure 21.9

If a CIN III abnormality progresses, the abnormal cells penetrate through the basal layer. Provided they have not become deeper than 5mm, this abnormality (micro-invasive) can still be regarded as pre-malignant.

What are the symptoms of pre-malignancy of the cervix?

It was thought that there are none and that symptoms only appear if the cervix has become frankly malignant. Even when a doctor examines the cervix, it is not possible to recognise pre-malignancy without the aid of special screening tests.

Recent evidence indicates that post-coital bleeding may be associated with pre-malignancy.

Should women with postcoital bleeding be referred for colposcopy? (2006)

What are benign and malignant tumors?

A tumour is essentially a swelling. The cells of a benign (innocent) tumour look normal under the microscope and there is no suggestion of them invading other tissues. The individual cells and their nuclei have similar shapes to that of normal cells. Malignant cells and their nuclei have different shapes and they invade and destroy surrounding tissues.

There are many specialised cells in the body, each having its own function. Each can form innocent or malignant tumours. There are a large variety of tumours with different causes and thus cancer is not one disease. Each cancer may have its own set of symptoms. The different cancers respond to treatment in different ways.

Why have I developed a pre-malignant condition of the cervix?

Pre-malignancy and malignancy of the cervix tend to be associated with sexual activity suggesting the possibility of transmission of a causative organism. Starting sexual activity at a young age, multiple partners and smoking are known factors.

It took many years to fathom out the culprit which proves to be the wart virus (Human Papillomavirus -HPV). From 1997, it has been possible to screen for the presence of this virus in routine clinical practice. The test is slightly expensive.

Eighty per cent of sexually active females will become infected with this common virus at some point in their lifetime. Approximately 20 million people are currently infected with HPV. At least 50 percent of sexually active men and women acquire genital HPV infection at some point in their lives. About 6.2 million Americans get a new genital HPV infection each year.⁰⁷⁰¹ Over 40 types of HPV infect the genital epithelium, and it isnow widely accepted that cervical infections by approximately15 carcinogenic types cause virtually all cervical cancer worldwide. In addition to HPV types 16 and 18, types 31, 33,35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66should be considered probably carcinogenic. Approximately 70% of cervical cancers are caused by HPV types 16 or 18.

What is colposcopy?

A special microscope (colposcope; Figure 21.8) allows the gynaecologist to magnify the cervix and define the area of abnormality. The cervix is visualised as when taking a smear. Dilute acetic acid is applied and this makes the abnormal area appear white (aceto-white). The colposcopist then looks at the blood vessel pattern (a green filter assists visualisation). Areas of mosaicism and punctation are examples of commonly seen abnormality (Figure 21.9). With local anaesthetic, tiny biopsies may be taken. These are sent to the laboratory where the pathologist can advise further about the severity (Figure 21.10).

Figure 21.8

Figure 21.9

Figure 21.10

There is evidence that there is a tendency to anxiety and depression⁰⁸⁰² associated with referral for colposcopy and this has an adverse effect on sexual function.⁰⁸⁰¹

What treatments are available for pre-malignant conditions of the cervix?

From the information obtained from the smear, colposcopy and biopsy, the gynaecologist can advise on appropriate treatment options. Mild degrees of abnormality (mild dyskaryosis / CIN I) may return to normal and there are times when they may be left untreated but kept under careful review by repeated smears and colposcopy.

The more severe abnormal areas will probably need to be destroyed. This can be achieved by removing them surgically (knife cone biopsy) or with a heated loop removing a cone (LLETZ is a large loop excision of the transformation zone-Figure 21.11). The cervix may be frozen (cryotherapy; Figure 21.4) or destroyed by cautery, cold coagulation (this still involves heat) or laser.

Figure 21.11

Figure 21.4

Historically diathermy knife cone biopsy and were the preferred treatments. The advent of laser allowed colposcopically directed ablation of the abnormal area. The disadvantage of laser was that it destroyed all the abnormality but there was no excised tissue for analysis.

The LLETZ has become popular because it treats the abnormality and the removed tissue can be analysed histologically (microscope examination. It has allowed a see and treat policy with assessment and treatment at the first visit. With ablative treatment a colposcopically directed biopsy is required before treatment.

There has been accumulating evidence that LLETZ is associated with subsequent premature delivery and this in turn increases the risk of damaging or losing the baby. There may, therefore, be a trend to return to ablative treatments. There may also be a case for less treatment of low grade abnormality. The chance of a CIN I lesion becoming malignant is 1% and 5% for CIN 2 - 5%.⁹⁸⁰¹ The appropriate treatment of premalignant conditions of the cervix requires review. Ultrasound assessment of the cervix may be appropriate in pregnancy for those who have had excision operations on the cervix to determine those at risk and perhaps consideration of a cervical circlage procedure. One study, however, showed no reduction of premature delivery with prophylactic cervical cerclage.⁹⁸⁰¹The majority of CIN 1 lesions regress within 2 years.⁹⁹⁰² At one time after treatment local antibiotic vaginal cream was prescribed to be used as this was thought to reduce the chance of infection and promote healthy healing. A study, however, has shown no benefit.⁹⁸⁰¹ Sexual activity should be avoided for at least three weeks and internal sanitary protection for four weeks.

Can pre-malignant conditions of the cervix be cured?

Pre-malignant changes are invariably cured by destroying the abnormal area as described above. Sometimes treatment may have to be repeated. Unfortunately, it is not possible to remove every Human Papilloma Virus, the cause of the abnormality, from the lower genital tract. After treatment, the virus usually lies dormant but it can become active again. It is, therefore, imperative that women treated for pre-malignant conditions of the cervix should be kept on long-term follow up.⁰⁷⁰¹

Topical antiseptic agent after large loop excision of the transformation zone: Results of a randomised controlled trial. (1999)

How can we know that a pre-malignant condition of my cervix will not Recur?

Your gynaecologist will recommend a plan for checking by PAP test (cervical smear)s and colposcopy. The Frequency and duration of repeat screening will depend on the severity of the treated pre-malignancy and the protocol of your clinic.

Cervical Cancer: How can we prevent cancer of the cervix? Gardasil - HPV Vaccine

The purpose of cervical screening is to prevent the appearance of invasive disease by the detection and appropriate treatment of pre-cancerous abnormalities.

There is compelling evidence that carcinoma of the cervix is associated with the human papilloma virus (HPV), which is transmitted during sexual intercourse. There are many strains of HPV. Types 16 and 18 are the two most commonly found in association with pre-malignancy and malignancy. When both partners enter marriage as virgins and remain faithful to each other, carcinoma of the cervix is rare. This explains why the disease is uncommon in religious communities that adhere to these principles. The sheath provides protection against sexually transmitted disease.

Cells have the potential to become malignant. This probably happens fairly frequently but the immune system usually destroy the abnormal ones (Q32.1).

The principles of screening are discussed in screening tests. Carcinoma of the cervix is a ‘surface’ disease. With a vaginal speculum the cervix can be readily visualised and cells sampled. There can be little doubt that screening has reduced the incidence of carcinoma of the cervix. Studies suggest that since the introduction of screening there has been a reduction of about 70%. Despite screening with cytology there remains a 30% incidence of malignancy. There is, therefore, a need for further improvement.

Liquid-based cytology involves placing sampling with a brush rather that a spatula and the brush is shaken into a liquid rather than producing a slide. This may prove to be more accurate than conventional smears.

Recently, there has been the development of a vaccine for immunisation against pre-malignancy and malignancy of the cervix - Gardasil - Sanofi Pasteur MSD. It has been suggested that vaccination will reduce the risk of cervical cancer by 70%.⁰⁶⁰⁵HPV Types 16 and 18 cause 70% of cervical cancer cases, and HPV Types 6 and 11 cause 90% of genital warts cases.

Gardasil may not fully protect everyone and does not prevent all types of cervical cancer, so it is important to continue regular cervical cancer screenings. Anyone who is allergic to the ingredients of GARDASIL should not receive the vaccine. GARDASIL is not for women who are pregnant. GARDASIL will not treat these diseases and will not protect against diseases caused by other types of HPV. GARDASIL is given as 3 injections over 6 months and can cause pain, swelling, itching, and redness at the injection site, fever, nausea, and dizziness. Only a doctor or healthcare professional can decide if GARDASIL is right for you or your daughter.

Prophylactic HPV Vaccines. (2007-01)
Review of current knowledge on HPV vaccination: An Appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening. (2007-02)
Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland. (2007-03)
Ensuring access to HPV vaccines through integrated services: a reproductive health perspective. (2007-04)
Seroprevalence of human papillomavirus types 16 and 18 in the general population in Taiwan: Implication for optimal age of human papillomavirus vaccination. (2007-05)
How will HPV vaccines affect cervical cancer? (2006-01)
Improved endocervical sampling and HPV viral load detection by Cervex-Brush Combi. (2006-02)
Prospects for cervical cancer prevention by human papillomavirus vaccination. (2006-03)
HPV vaccination with Gardasil: a breakthrough in women's health. (2006-04)
Using the new HPV vaccines in clinical practice. (2006-05)
The human papillomavirus vaccines. (2006-06)A study of women's knowledge regarding human papillomavirus infection, cervical cancer and human papillomavirus vaccines. (2006-06)
A study of women's knowledge regarding human papillomavirus infection, cervical cancer and human papillomavirus vaccines. (2006-07)
Assessment of knowledge and attitudes of young uninsured women toward human papillomavirus vaccination and clinical trials. (2006-08)
Pediatricians' intention to administer human papillomavirus vaccine: the role of practice characteristics, knowledge, and attitudes. (2005-01)
Human papillomavirus vaccine as a new way of preventing cervical cancer: a dream or the future? (2004-01)
Human papillomavirus vaccine as a new way of preventing cervical cancer: a dream or the future? (2004-02)Primary screening for cervical cancer precursors by the combined use of liquid-based cytology, computer-assisted cytology and HPV DNA testing. (2002-01)
Acceptability of a human papillomavirus (HPV) trial vaccine among mothers of adolescents in Cuernavaca, Mexico. (2001-01)Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. (1999-01)International incidence rates of invasive cervical cancer after introduction of cytological screening (1997)
Treatment of pre-invasive conditions during opportunistic screening and its effectiveness on cervical cancer incidence in one Norwegian county (1997)Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing. (1997-03)

Is there a reason to screen for HPV (Human Papilloma Virus)?

It is now possible to screen for human papillomavirus which is the culprit for pre-malignant and malignant conditions of the cervix. This has only recently become available for clinical practice although it has been under investigation for more than ten years. There has been skepticism about the clinical value of HPV testing particularly on the part of those who may be required to provide funding. Studies indicate that when the HPV test is positive there is a 50% chance that there will be a high grade of CIN.

Those responsible for funding healthcare perceive an additional expenditure should HPV testing be widely adopted. They point out that 20% of young women are likely to be infected with the virus but the majority will not go on to develop pre-malignancy.

About 1-2% of smears are reported to be unsatisfactory and a repeat test is re quested by the laboratory. This causes stress for the patient who assumes that there is a major problem. It has been estimated that the annual cost of repeat smears in the USA amounts to $3 billion. Those with experience of combined cytological and HPV testing suggest that the referral rate for colposcopy may be reduced by 30%. They also suggest that, from an economic point of view, the combination of cytology and HPV testing results in a cost reduction. In Switzerland, there has been a 10% reduction in the overall cost of screening since the introduction of HPV testing. In the UK it has been estimated that the worst scenario of introducing routine HPV screening in conjunction with PAP test (cervical smear)s would be a neutral effect on funding but there could be a ?30 million saving.

In the UK 5.5million smears are taken annually. It would seem that if the combination (PAP test (cervical smear) and HPV test) results in fewer false negative results and less unnecessary intervention, HPV testing would prove to be cost-effective. The value to the patient of better reassurance that she is having more effective screening cannot be measured.

Currently PAP test (cervical smear)s are usually read by trained technicians. A typical slide sent by the doctor will include about 30,000 cervical cells. Large numbers of cells are assessed under low power microscopy and the majority of cells are evaluated. Abnormal cells are more obvious under higher magnification but time precludes checking all the cells. Computer systems such as Papnet are under investigation to see if they could improve accuracy.

One of the potential problems of introducing HPV testing is that perhaps 25% will prove positive potentially increasing the need for colposcopy many fold.

The exact place of HPV testing has yet to be determined.
New Developments

LIQUID BASED CYTOLOGY

One of the main problems with the conventional smear is that up to 80 per cent of the cells collected are not transferred from the spatula to the slide. In addition, excessive blood and mucus lead to unsatisfactory smears, necessitating recall.

In October 2003, it was announced that liquid based cytology (LBC) would be introduced in England and Wales (Scotland already had it). The principle ofLBC is that instead of smearing the spatula across a slide, it is rinsed in a vial of preserving solution. A small plastic brush is used, because cells tend to stick to wooden implements. In the laboratory, the vial is agitated to distribute the cells evenly, then they are filtered out under pressure to produce a thin layer on a slide. One advantage of this is that the machine always takes the same number of cells.
The main advantage ofLBC is that it greatly reduces the number of inadequate smears; in the UK pilot study, the inadequate rate fell from 9.1 per cent with conventional cytology to 1.6 per cent with LBC.2 Anybody who deals with women in the screening programme knows that the anxiety caused by inadequate smears is enormous and if there were no other advantages to LBC, it would be worth introducing for this alone.

Another advantage is that thin layer cytology is easier to read because there are no clumps of cells and no blood or
mucus obscuring the view. Screening times in the laboratory are reduced, so throughput is increased and results are made available more quickly.

Studies have also suggested there may be a reduction in the number of borderline smears reported and greater detection of high-grade CIN. However, a recently published randomised trial conducted in Italy3 showed no increase in the sensitivity ofLBC compared with conventional cytology. There are conflicting results in different studies and it is likely that the level of staff training and quality assurance is important - it is difficult to show improvements where the standard is already very high. It is also apparent from the pilot studies that there is a learning curve for LBC. A cost analysis showed that the reduction in inadequate smears alone makes LBC cheaper in the long run than conventional cytology, although this does not take into account the considerable start-up costs.

COMPUTERISED SLIDE SCREENING

LBC makes it easier to introduce computerised slide screening, a major step forward. In this, a computer is fed numerous images of normal and abnormal smears and programmed to draw attention only to those fields it considers not completely normal.

Severe dyskaryosis: studies suggest that liquid based cytology can detect more high grade CIN than conventional methods

Research has shown that this technology holds great promise. The computer identifies 22 fields of interest most likely to have abnormal cells, which are then examined by a cytologist.

In the study, LBC slides obtained in a large population under routine clinical practice and read using the computerised system detected significantly more histological high-grade cervical disease than conventional cytology slides. A study based on the same cytologists showed that the mean time taken to evaluate and report LBC slides using the computerised system was 41 minutes per slide, compared to 10.6 minutes per slide for conventional cytology.

Another useful aspect of LBC is that the same sample can be used for other tests, for example, chlamydia, gonorrhoea and HPV. This opens up the possibility of 'reflex' HPV testing for triage - if a woman has a borderline smear, her LBC sample can be tested for HPV; without the need for another examination. If' the HPV test is negative, this would be reassuring, because it virtually rules out any possibility of disease. This was tried in some pilot sites, but a problem arose because HPV resting gives many false positives. This approach still needs some thought, but is another string to the bow of LBC..

Support Groups

Members of a support group, provide each other with various types of help and information for a particular shared difficulty.

The support may take the form of providing relevant information,

relating personal experiences,
listening to others' experiences,
providing sympathetic understanding and
establishing social networks.

A support group may also provide ancillary support, such as serving as a voice for the public or engaging in advocacy.

Support groups maintain interpersonal contact among their members in a variety of ways.

Support groups also maintain contact through printed information rich newsletters, telephone chains, internet forums, and mailing lists.

Support groups offer companionship and information for people coping with diseases or disabilities. Support groups may not be appropriate for everyone, and some find that a support group actually adds to their stress rather than relieving it.

Evaluation of the quality of Web sites is discussed in (internet information). You may find that several general women's health sites may help you (internet information). The following are more specialised relevant Web sites:-

This page was last reviewed 12th March 2008

HPV Support Group:

American Society of Clinical Pathologists

Box WWW

2100 West Harrison Street

Chicago

IL, 60612-3798

Cancer BACKUP,

3,Bath Place

Rivington Street

London EC3 3JR

The provision of information leaflets before colposcopy beneficial? A prospective randomised study. (1999)

Women's Health

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This is the personal website of David A Viniker MD FRCOG, Consultant Obstetrician and Gynaecologist at Whipps Cross University Hospital, London - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.

I do hope that you find the answers to your women's health questions in the patient information and medical advice provided.


		Pap Smear test- - Normal / Abnormal - premalignant cells - colposcopy - HPV

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Pap Smear test- - Normal / Abnormal - premalignant cells - colposcopy - HPV