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Liquid-based cytology versus conventional smears

C Mary Anderson
BM BCh DCH DIH MRCGP
GP Principal
Heaton Moor Medical Centre
Stockport
Member of Stockport Cervical Cytology Advisory Group
E:AndCM@aol.com

Cervical screening has encountered many problems in England, from "inadequate" smears and a shortage of cytoscreeners, to adverse publicity and litigation. The National Cancer Plan promises improved technology.(1) Liquid-based cytology (LBC) is being considered.

What is liquid-based cytology?
Despite media headlines, LBC is not a "new smear test"; it is simply a technology aimed at improving the traditional smear test. It involves suspending cells in liquid before examination by conventional microscopy.

Will we all be using LBC by 2005?
It depends on the National Institute for Clinical Excellence (NICE). In 2001 its guidance stated:

"Research evidence suggests that LBC could provide important benefits, but the quality of the evidence is variable and some areas of uncertainty remain. Therefore the Institute advises that although there is insufficient evidence to justify the introduction of LBC technology across England and Wales at this time, it is likely that LBC will lead to improvements in cervical screening. To help to decide how to use LBC, the Institute has ­recommended pilot projects to assess the effects, costs and practical implications (training, supplies, storage, disposal) of introducing LBC technology into the cervical screening ­programmes in England and Wales.(2)"

HPV (human papillomavirus) testing is being piloted at the same time. NICE will report on these pilots in 2003.
Meanwhile, the Scottish Health Minister, Malcolm Chisholm, announced in March 2002 that Scotland will invest £2.75 million in the Scottish Cervical Screening Programme to implement LBC.

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What does LBC mean for women?
Results show a fall in "inadequate" smears from 9% to 2% approximately with LBC.(3) This means fewer repeats and fewer referrals for colposcopy. However, with LBC there will be a small increase in abnormal smears (it is not known by how much in routine practice). In theory there may be fewer cancers missed, but this has not been proven. Other tests could be done on the same sample. In some places the private sector is already offering four tests on one sample - LBC smear, chlamydia, gonorrhoea and HPV testing.

HPV testing: a separate problem
HPV testing is a minefield, because nobody knows what the results mean or the best action to take. Women may come to us in distress about their results, and we simply do not have sufficient information to advise them. I believe we should offer HPV testing only as part of an academic clinical trial, until such time as it can become part of the National Cervical Screening Programme. Trials are in progress.

What does LBC mean for smear takers?
A speculum is still required to visualise the woman's cervix, but instead of the wooden spatula we use a soft plastic "broom", and instead of having to spread the smear onto a slide, a fixative solution is added, allowed to dry, and put in a plastic box - all we have to do is rinse the cells off into a vial of special liquid. There are no slides to get broken in transit, and the cells can't dry out. Studies show that smear takers like LBC.(3) But we have even greater responsibility to sample the cervix properly, because there is no longer the safeguard of seeing whether there is not enough material on a slide.

What does LBC mean for laboratories?
A big upheaval, special equipment and training. Vials are processed in the lab, a monolayer of the suspended cells is put on a slide, fixed and stained for examination under the microscope in the usual way. The "cell preps" are said to be cleaner and easier to read, with no overlap, no debris, blood or pus (see Figure 1). There is also scope for some automation of slide preparation and for future semiautomated reading of slides. In fact, LBC proved very popular with staff at labs in the Scottish pilot who didn't want to go back to the old method.(3)

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What if NICE turns down LBC?
If LBC is not implemented nationally, then primary care trusts (PCTs) could theoretically negotiate with a large LBC-converted laboratory to commission or "buy in" LBC services. But the decision would be very difficult, given existing areas of uncertainty. The New Zealand Health Technology Assessment(4) and the recent debate in the journal Cytopathology(5,6) are essential reading on this topic.

What should we do while we are waiting?
Aim for best practice. There is room for improvement in at least four areas:

  1. Refer urgently to gynaecology (not colposcopy) if there is suspicious cervix or "red-flag" history.
  2. Continue to check addresses and remind women to inform us when they move, to minimise the number of women with abnormal smears lost to follow-up.
  3. Don't screen women under the age of 20. This move, recommended by the Screening Programme, will reduce the number of smears by over 50,000 a year, which in turn will save a lot of unnecessary colposcopy and anxiety for young women.(7,8)
  4. Avoid unrealistic expectations. Give unbiased information for informed consent.

The advantages of LBC

  • Quicker for smear takers.
  • Slides "cleaner" and more evenly spread.
  • Quicker and easier for cytoscreeners.
  • Fewer "inadequates" and hence less repeats.
  • Fewer colposcopies.
  • Potential for automation or semiautomation.
  • Potential for HPV testing on the same sample (and/or chlamydia and gonorrhoea).

The disadvantages of LBC

  • Not tested against long-term outcomes (ie, never proved better at reducing cervical cancer).
  • Only a fraction of the smear cells are on the slide (said to be more representative, but ­cytopathologists say they lose "architectural clues": eg, the actual groupings of cells in ­conventional smears can help the diagnosis).(5,6)
  • More expensive.
  • Reporting profiles will change, so new standards will need to be set.
  • May be more minor abnormalities of unknown ­significance. This will need watching and a strategy worked out regarding what to do if this increases? The last thing we want is to create more "abnormalities" and be trapped into more ­overinvestigation and ­unnecessary treatment.
  • LBC could be a "red herring"? Are the main problems with cervical screening elsewhere? There are far too many minor abnormalities, and some cervical cancer deaths still occur despite proper diagnosis and treatment of abnormalities. Also, how many women die of cervical cancer because they failed to attend colposcopy when referred after smear abnormality?

The future: a five-year forecast?

  • LBC for the screening programme by 2005?
  • Selective HPV testing - for example, to triage mildly abnormal smears in women over 35?
  • Semiautomated reading of slides?
  • New markers of cervical disease (such as the "MCM" protein trials in Manchester and Cambridge)?
  • Vaccine against cervical cancer?
  • Antiviral treatments to cervix?
  • Could routine mass cytology become obsolete?

References

  1. Department of Health. National cancer plan. HMSO: London; 2001. Available from URL: http://www.doh.gov.uk/ cancer/cancerplan.htm
  2. NICE website. Available from URL: http://www.nice.org.uk
  3. Scottish Cervical Screening Programme. Steering Group Report on the feasibility of introducing liquid based ­cytology. 2002. Available from URL: http://www.show.scot.nhs.uk/sehd/publications/screeningliquidcytology2.pdf
  4. Broadstock M. Effectiveness and cost effectiveness of automated and semi-automated cervical screening devices. A systematic review. New Zealand Health Technology Assessment (NZHTA) Report. 2000;3(1). Available from URL: http://nzhta.chmeds.ac.nz/ nzhtainfo/csv3n1.htm
  5. Herbert A, Johnson J. Is it a reality or an illusion that liquid-based cytology is better than conventional cervical smears? Cytopathology 2001;12:383-9. (also correspondence by Moseley R. Cytopathology 2002;13:135-6).
  6. Slater DN. For debate: ethical ­considerations of gynaecological liquid-based cytology and human ­papillomavirus studies. Cytopathology 2001;12:251-6.
  7. NHS Cervical Screening Programme website. Available from URL: http://www.cancerscreening.nhs.uk
  8. Cervical Screening Programme (Statistical Bulletin) 2000/2001. Available from URL: http://www.doh.gov.uk/pdfs/sb0122.pdf

Resources
Concerns should be raised with the local ­multidisciplinary cervical cytology advisory/steering group (every district has one)
National Cervical Screening Programme
The Manor House
260 Ecclesall Road South
Sheffield S11 9PS
T:0114 271 1060
F:0114 271 1089
W:www.cancerscreening.nhs.uk
E:info@cancerscreening.nhs.uk

Forthcoming events
Courses and conferences
by Marie Curie Education
W:www.mariecurie.org.uk/about/scrcourses.htm
Summer 2004 National Screening Conference UK (every 2 years)
E:screening@westminster.com
15 April 2003 EUROGIN 2003: Global Challenges in Genital Infections and Cervical Cancer Prevention Paris
E:admin@eurogin.com