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ESSAY 141 - CERVICAL SCREENING

Posted by uma M.
Cervical cancer is 2nd most common cancer worldwide. over 400000 cases of cervical cancer are diagnosed every year. 2/3 rd of these are from developing countries. developed countries like UK has less incidence of cervical cancer and this is largely due to screening. In UK cervical screening programme is largely sucessful.About 81 % of population being covered, NHSCSP effectively reduced mortality due to cervicalcancer by1/3rd & incidence by 2/3 rd. In year 2002 deaths due to this disease has
been recorded as just 927. NHSCSP screened women starting(Ist call)at20yrs, recall every 5yrs till65yrs.It used conventional pap smear for screening.

No test is 100% accurate. similarly cervical screening using papsmear reached limitations.with conventional screening there are around 6-10% of smears reported as inadequate.this increaseswork load on staff,cost of screening,and anxiety,fear on behalf of patient.women should be recalled agin for smear.False positive rates, increase unnecessary investigations in search of
cancer and increase cost toNHS.

These problems can be over come to a certain extent.Implementation of new technology,liquid based cytology(LBC)is likely to usefull to reduse inadequate smears.With conventional smear only proportion of cells are trasferred to slide.In LBC smear is taken as routine,then spatula is rinced in
methanol solution for transfer to lab.after centrifugation a thin layer of smear is made and remainder stored.smear is reported . this reduses unsatisfactory smears, false negatives as there
will be no artefacts.3 pilot studies inUK have shown this to be effective & NICE recommends this to be implemented into NHSCSP.Now it is introduced into NHSCSp.From studies it has shown to reduce inadequate smears,pressure on skilled work force, level of anxiety in women.This also has quicker reporting , clearer samples.Roll out is likely to take place in next 5 yrs.But this is assosiated with additional cost of 10million pounds
.likely to be cost effective in longterm.LBC has additional advantage that fluid can be utilised for HPV testing if needed avoiding women attending again.

In order to improve specificity it would be ideal to screen at risk group.But with cervical cancer all women who are sexually active are at risk of this. It has been shown that this disease
has a long preinvasive stage and screening programme aims to detect this stage .Young women < 25yrs have only small incidence of CIN and even if present would take long before it turns malignant,leaving ample time for diagnosing even if screened later. also in thesewomen HPV infection & changes assosiated with this are common causing similar cytological abnormalities.Immature cervix of young might show dysplastic changes (false positive).Similarly CIN is disease of women of young age. IN Women >50 yrs CIN is reported rarely. It has been shown in a study form UKthat in women who had 3 negative smearsmost recent taken no more than 3 yrs before if stopped
screening at 50 yrs ther is only remote possibility of she developing cancer. Also natural history & progression are such that these women are unlikely to to develop disease.Taking this into consideration screening can be stopped or frequency reduced after 50yrs to improve specificity.
NHSCSP has now accepted that it would make first call at 25 yrs,screen every 3 yrs till 49yrs.From 50 -64 yrs it would recall every 5 yrs.stop screening at 64yrs.Only if women is not screened
after 50 yrs then you are justified in screening after 64 yrs.

Role of HPV testing to improve sensitivity is to be tested further.It is proven that 99.7% of cancers will be HPV posotive . it has shown to have high negative predictive value,there by if tested negative can reduce frequency of screening further.Positive test does not have any meaning unless it is persistent as 20% in reproductive age group test positive for HPV.most are transient .persistence of infection for >24 months
of high risk HPV 16,18,31,33,35 has shown to lead to cancer.ARTISTIC by MRC would answer questions of improving sesitivity, specificity and contribution for inadequate smears.
Posted by narmin B.
Cervical screening is associated with a considerable ?false-positive? rate and a high rate of inadequate smears. How can this be improved?


High rate of false positive and inadequate smear reports will lead to patient?s anxiety, increased workload in colposcopy clinics and over treatment of patients. There are various reasons for these kinds of results which include incorrect sampling of the cervix and poor preparation of the slide in primary care, inadequate preparation and incorrect interpretation in cytology department, presence of blood, leucocytes, previous biopsy, patient?s conditions like pregnancy, postpartum, menopause and infection which can make interpretation difficult. Not only improvement in the standards of work in primary care and cytology departments are required, but more accurate methods of cervical screening should be employed.

In the primary care correct technique of taking smears should be used. Smears should be taken from transformation zones. As taking smear from only endocervical canal will provide inadequate cells for interpretation and results in inadequate report. Similarly fixation of the smear is important as air dried smears are associated with more inadequate reports. Alcohol fixation of the slide is associated with better results.


Interpretation of a cervical smear can be difficult due to the presence of blood, leucocytes, thick smear and previous biopsy which can result in false positive test. Adequate time should be allocated for correct interpretation. Patient condition and use of hormonal preparation should be considered in interpretation of the smears. Litigation is another area which may influence on the interpretation of the smear by cytologist. As smear tests are being performed every 3 to 5 years, where there is any doubt about interpretation of a smear, it may be reported as positive in order to be referred to colposcopy clinic for further assessment and prevent any misinterpretation.


Other technologies can be employed to reduce the rate of false positive and inadequate results . Liquid based cytology (LBC) involves a suspension of cells from the cervical scrape sample and this is used to produce a thin layer of cells on a slide .This reduces the obscuring elements such as leucocytes and blood, making interpretation easier. The sensitivity of screening will be increased and the rate of referral to colposcopy clinics will be reduced. However this technique is not currently a routine method in the UK. It has financial effect and need capital investment in the start of programme. Also training and different methods of taking smear may be required.


Over 90% of premalignant and malignant cervical conditions are associated with Human papilloma virus (HPV) type 16, 18 and 32 infection. Detection of HPV can be used as an adjunct to cervical cytology. It can be used where there is inadequate smear. If the patient was HPV positive then referral to colposcopy clinic is necessary. This test is not routinely available in the UK. Its introduction in the cervical screening programme has its own costs and need extra manpower. However it reduces the workload in colposcopy clinics and prevent over treatment of the patients.

There should be continued audit and training in order to improve the standards of cervical screening programme. Also liaison between cytology and colposcopy clinics is required to correlate the result of histology and cytology which may be helpful in understanding the different patterns of cytology.



Posted by Rani M.
Incidence and mortality of cervical carcinoma haas reduced considerably over the years in U.K. with the adoption of universal cervical screening by NHSCSP. Though PAP smear has good sensitivity, false positive rates are upto 20 % and inadequate smears are reported in 8-9% smears.When a cervical smear is taken only a proportion of the cells scraped from the cervix are actually transferred to the slide and these may be partly obscured by both red and white blood cells.
Liquid based cytology has been recommended by NICE to overcome these problems. LBC involves the taking of the smear by a plastic device from which cells wash off more readily than from a wooden spatula. also several optimal thin layer smears can be made and the remainder of the cells are stored. this reduces the incidence of inadequate smears from 9% to 1-2 %.Smears made by the LBC specimen have a clear background and are thus easy to read and interpret. Results are quicker and false negatives are low. It also has potential for incorporating HPV test in the supernatent.
Another method suggested to improve the results is HPV detection. HPV is detected in 99.7% of cervical carcinoma cases.Combining cytology with HPV detection increases sensitivity for CIN detection to 96%.also HPV testing has good negative predictive value.this wll help in triaging borderline and low grade smears.majority of woman with bordrline smears will be negative for CIN and use of HPV in these case will help in upgrading or downgrading( if HPV negative) them; thus optimising the referrals to colposcopy clinic, and avoid creating unnecessary anxiety.Disadvantage are 75 % of woman are HPV positive at some stage though only 2-3 % of them will develop CIN. 70% of woman with HPV will test negative with in 2 years time.Thus this test should be used to supplement cytology and not to replace it.
Another way to reduce false positive is by not screening woman before 25 years of age.HPV infection rate is maximum in this age group though cervical carcinoma is rare.also false positive are high due to physiological metaplasia Due to long natural history of CIN and cervical carcinoma ,ample time is still provided for detection after these years
testing for molecular markers in the protein from cells of smears is suggested but this is still at research setting...
Posted by vijaya L.
A false positive result of a cancer screening programme is associated with considerable psychological upset and unnecessary use of resources like colposcopy and medical personnel.
An automated computerized system has been thought to decrease the manual errors of overloaded cytopathologist. But it is still offered under the clinical trial basis. The abnormal smears picked up by the mechine should be viewed manually and a few random smears from the normal category are also to be examined manually to check the accuracy.
The cytopathologists who provide the service of screening should audit the results of their smears regularly and compare with compare with quality assurance standards set by NHSCSP.
Colposcopy centers send the results of colposcopy and biopsies of the abnormal smears to the referring professionals and if more than 30% of the time colposcopy fails to find any pathology the concerned professional should recheck his technique and consider retraining.
HPV is found in all most 100% of invasive cervical cancer. Hybrid capture of high risk HPV viral DNA has been found to be useful in categorizing the ASCUS smears into high and low risk groups. Similar triaging is under study for mild dysplastic smears to chose a high risk category which would benefit from early referral to colposcopy.
A study is also being done to find out whether women can be screened by HPV first and only positive ones can be followed up by the smears, this might reduce the false positive rate but is fraught with problems like transient nature of HPV infections in some women. This could probably be overcome by retesting for persistence of HPV infection after about 6 months.

Inadequate smears are also a cause of considerable distress to the women who needs to be recalled and the procedure redone.
Clearing the mucus of the cervical surface before taking the smear may improve the smear quality.
Using the ectocervical spatula first followed by the endocervical broom can reduce the blood staining of the smear, which would impair the study of the cellular pathology.
Regular audit of the unit or single professional?s practice for the rate inadequate smears, and rechecking their technique and slide fixing method and transfer to the lab are absolutely necessary.
Liquid based cytology which collects all the material that is sampled into the fixative solution and makes a thin smear on the slide after centrifugation eliminates the subjective variation in the smearing of a slide and provides a good slide for adequate viewing. But it is expensive
Many new technologies have made inroads into the cervical screening programme to make this success story cost effective as well.

Posted by Nibedita R.
Aim of cervical screening is to reduce incidence and death from cervical cancer by detecting early cytological changes and instituting appropriate treatment.

The NHS cervical screening programme was introduced in 1988. Currently over about 80% eligible (20-64yrs) women are screened every five yearly. Although the comprehensive programme has achieved significant reductions in both incidence and death (60-70%) from cervical cancer but it has poor sensitivity (44-54%) with a large number of false positive and false negative (2.4-26%) cases and inadequate smears (2-10%).
Several changes have been proposed in the programme. These include age group, liquid based cytology (LBC) and interval of screening. These changes are largely to improve the sensitivity, reduce false positive rates and inadequate smear rates.

New recommendations are for three yearly screening for women between the age of 25-49 years and five yearly screening between 50-64 years. In younger women (<25yrs) cervical cancer is very rare and screening is not routinely done unless risk factors like sexual life has started very early, multiple sexual partners or a history of sexually transmitted infection are present.
At younger age, immature cervix sometimes shows changes, which are picked up as positive and lead to unnecessary anxiety and treatment. HPV infection is very common in younger (20-24yrs) women, which causes cytological abnormality and increases false positive rates. Most of these abnormalities would resolve spontaneously without treatment.

Estimated figures are that three yearly screening prevents 84% cervical cancer compared to 73% for five yearly screening in 25-49 age groups without increasing false positive rates. In older women five yearly screening can prevent 83% cancer and no extra benefit would be gained from three yearly screening. So exclusion of age 20-25 years from the programme will reduce false positive smears with significant decrease in work load and also be cost effective.

The new recommendation includes liquid based cytology testing. This has been evaluated from pilot studies carried out in UK to significantly decrease the number of inadequate smears (from 9% to 2%) without decreasing sensitivity. Inadequate smears to large extent are due to sampling error or presence of blood, mucus or pus.
In fluid based system, processing of cervical sample attempts to reduce sampling error and improve specimen adequacy by suspending cervical cells in a liquid solution by removing obscure material (mucus or pus). This also provides a faster turnover time in the laboratory. This would be beneficial in terms of an early report to relieve anxiety and uncertainty as well as the need for repeat smear.

HPV is the most identifiable risk factor for cervical cancer and CIN. Over 90% of high grade CIN will contain HPV DNA of oncogenic type. Most common type is HPV 16, but several others are 18,31, 33 and 45. HPV testing is feasible from the sample of LBC. Combined cytology and HPV testing has found a sensitivity of 96 % and positive predictive value of 64% of detecting CIN, this can by improved by subtype testing. Approximately 75% of borderline smear are in fact normal. HPV testing in borderline nuclear abnormality can increase sensitivity in detecting high grade CIN and could reduce the number of women referred to colposcopy by around 50%. In women with mild dyskaryosis, referral to colposcopy can be done on the basis of HPV testing, if a repeat smear after 6 months is found to be persistently positive.