Clinical trial finds repeated smear is best treatment option for slightly abnormal smear test result
MEDICAL RESEARCH COUNCIL MEDIA RELEASE
MRC/48/09
Wednesday 29 July
The results of a clinical trial comparing treatment options for women who have a slightly abnormal smear test result are published today in the British Medical Journal. Overall the TOMBOLA trial has found that repeat cervical smear tests are as effective in managing an abnormal result than the more invasive examination and tissue biopsy (colposcopy) option.
The trial also found that if women are referred for colposcopy - whereby the vagina and cervix are examined using a microscope and a tissue sample is taken from the cervix if abnormalities are seen – removing just a small amount of tissue at the time of examination and then recalling women only if the laboratory reports abnormalities, is as effective as the more radical approach of removing the whole zone of possibly abnormal cervical cells on the first colposcopy visit.
More than 4,000 women living in Aberdeen, Dundee and Nottingham participated in the TOMBOLA (Trial of Management of Borderline and Other Low Grade Abnormal Smears) trial.
The study was funded by the Medical Research Council and the NHS in both England and Scotland. It began in 1999 with the aim of identifying the best follow-up treatment regime for women who have a slightly abnormal smear test result.
On behalf of the TOMBOLA group, principal investigator Professor Norman Waugh of the University of Aberdeen said: ‘‘The results of the first TOMBOLA trial show that it is just as effective to follow-up women with slight abnormalities by repeat smear in general practice, as by immediate referral to specialist gynaecology clinics.’’
The TOMBOLA trial was split into two parts; in the first trial women were either referred for colposcopy, or followed up by having a repeat cervical smear - scraping cells off the surface of the cervix.
It found that the less invasive option of repeat smear test follow-up was, on balance, as effective in detecting changes that might lead to cervical cancer as the more radical option of immediate referral for colposcopy. Women who had the repeat smear treatment option experienced fewer adverse side effects, for example pain and bleeding, than those who had a colposcopy. When repeat smear tests were compared to colposcopy little difference was found in ability to detect advanced changes within cells.
In the second part of the TOMBOLA trial, the women who had a colposcopy were divided into two groups to enable comparison of different ways of checking for abnormal cells. 1,000 women were randomly assigned to the ‘biopsy and selective recall’ group and 983 to the LLETZ group (large loop excision). In the LLETZ group, the entire area of abnormal looking cells was immediately removed. In the biopsy group up to four small areas of tissue were removed from any areas of cells that looked abnormal, women were then called back for further treatment if necessary.
Both tissue removal methods were carried out during colposcopy. Samples were then analysed in the laboratory to determine whether there were cell changes that were more advanced than indicated by the initial smear test.
All of the women in both groups were invited to have a colposcopy as an ‘exit examination’, three years after they were first seen in the trial to ensure that nothing was missed in either follow-up, that changes had regressed and that treatment had been effective. Overall, the results of these tests showed that biopsy and selective recall for LLETZ is as effective in detecting and preventing further cellular changes, than LLETZ at the time of colposcopy.
Explaining the impact the trial results could have on treatment options for women Professor Waugh concluded: “The less invasive biopsy and recall procedure has fewer side effects that removing a large area of tissue at the outset. Biopsy and selective recall provides the best balance between benefit and harm, as for some women large loop excision could be over-treatment. We are not looking for cancer at this stage, but for changes, most of which would never progress, but some of which would.’
“For example, if a woman is referred for colposcopy, the TOMBOLA trial shows that it is better to take a biopsy of a small amount of tissue, examine it in the lab and then only if cellular changes that suggest a risk of progression to cervical cancer are found, to recall the woman for further treatment. This is a less invasive treatment option that removing the whole area of cervical cells at the first appointment before the tissue has been examined to assess how advanced those changes are.’’
In one paper, the TOMBOLA group noted that follow-up by cytological surveillance cost less to the NHS than referral to colposcopy and in a previous paper, the TOMBOLA group published data on the financial costs to women, which reports that attendance at a colposcopy clinic cost women on average three times more than follow-up by repeat smear; £9.00 to attend for repeat smear, compared to £27.00 to attend a colposcopy clinic.
For further information and to arrange an interview with colleagues on this project, please contact Nicola Osmond-Evans in the MRC Press Office on 0207 670 5138 or press.office@headoffice.mrc.ac.uk
Notes to editors:
Original research papers
The following three papers are published online in the British Medical Journal:
‘Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial.’
‘Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.’
‘Options for managing low grade cervical abnormalities detected at screening: cost effectiveness study.’
After-effects reported by women following colposcopy, cervical biopsies and LLETZ, is published online in the BJOG: An International Journal of Obstetrics and Gynaecology, www.bjog.org July 2009; DOI: 10.1111/j.1471-0528.2009.02263.x.
Woolley et al for the TOMBOLA Group. UK cervical screening and the costs of time and travel. Published in the International Journal of Technology Assessment in Health Care 2007;23;232-239
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