Details of HTA project in progress
Last updated: 9 May 2012 - Next update due: 16 May 2012
Research type: |
Primary Research (e.g. trial) |
Project title: |
A multistranded study to determine the minimum cellularity required for the reliable assessment of Liquid Based Cervical (LBC) cytology samples |
Project ref: |
05/41/02 |
Cost: |
£339,251 |
Chief Investigator : |
Dr Lesley Susan Turnbull, Consultant Cytopathologist and Director, North West Cervical Screening Quality Assurance, Betsi Cadwaladr University Health Board |
Start Date: |
October 2007 |
Estimated date of publication in HTA journal series: |
Mid 2013. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
Liquid Based Cytology (LBC) was approved as the recommended method for preparing cervical samples in 2003. National pilot studies showed that this method was superior to conventional spread smears and reduced the inadequate rate from 10% to 1-2%. However, the number of cells required for these samples to be deemed adequate remains the subject of debate. There is a risk that samples may be described as negative when they are really inadequate and that abnormalities could therefore be missed. An adequate LBC sample is one in which sufficient numbers of cells are present to allow the detection of an abnormality were it to be present. This study aims to establish the threshold of cellularity which will minimise the risk of false negative reports. The first part of the study surveys current practice in laboratories throughout mainland UK using LBC for cervical screening and establishes the cellularity of a large cohort of inadequate, negative and abnormal slides. The second part of the study evaluates the ability of screeners to detect abnormalities of differing type and relative abundance. This will be done by preparing sets of slides which vary in their total cellularity and in the total number, type and relative proportion of abnormal cells. These will be presented to a large number of laboratories for independent evaluation. The results will allow an estimate of a level of cellularity at which most abnormalities are likely to be detected and will hence determine a safe minimum cellularity. This study is led by a team of international and national experts with many years of experience in cervical screening, liquid based cytology and the conduct and evaluation of clinical trials. |
Project Abstract: |
Setting: The study will encompass a large number of NHS Acute Trust laboratories which participate either in the NHS Cervical Screening Programme, the Scottish Cervical Screening Programme or Cervical Screening Wales and which have implemented Liquid Based Cytology (LBC) for population based cervical screening. Target Population: LBC samples and slides obtained from women between 25-64 who have presented for routine cervical screening. Health Technologies being assessed: The study will assess the only two LBC systems currently in use in the UK; the Cytyc ThinPrep® LBC system and the SurePath™ LBC system. Design Part1: 55 laboratories will be surveyed to establish the type of LBC system used, length of usage, LBC performance data and declared cellular threshold for LBC sample adequacy. 6,050 slides will be gathered from these laboratories (1,100 each of inadequate, low and high grade disease and 2,750 negative cases). These will be anonymised, randomised and redistributed to peripheral laboratories for cell counting according to agreed standardised protocols. Sample Size: Declared inadequate slides will be used to determine the distribution of cellularity in such slides. With a sample of 1,100 a proportion of say 5% falling above the specified threshold can be estimated with a 95% distance from the percentage to the 95% c.i. of 1.3%. Declared negative slides will be used to estimate the proportion falling below the specified threshold. With 2,750 slides a proportion of 1% falling below the required threshold can be estimated with distance from the percentage to the 95% c.i. of 0.4%. With 2,750 negative slides, 1,100 high grade and 1,100 mildly dyskaryotic slides, a chi-squared test of trend will have a power of 87% to detect a difference between 1% of negative slides falling below a threshold increasing to 2.5% in the mildly dyskaryotic cases and a power of 74% to detect a trend increasing from 1% to 2%. Statistical Analysis: An estimate of the proportion of slides falling above or below the specified threshold. Covariates for smear result, LBC system and relevant data from the survey of practice would be included in logistic random effects model. Analysis would be carried out using each laboratory's current threshold and that derived in part 2. Outcome Measures: Outcome would indicate how closely laboratories achieve declared criteria and levels derived by part 2. Statistical modelling may give some indications of practices (SOPs) that are more successful. Design Part 2: Serial dilutions of SurePath and ThinPrep cases with differing total cell counts, patterns of dyskaryosis and proportion of abnormal cells will be randomised with negative and inadequate cases of similar cellularities from Part 1 of study. 5,000 slides will be gathered in total. Each slide will have a total cell count and a total abnormal cell count performed by 2 of an expert panel of 4. The slides will then be redistributed to peripheral laboratories for morphological assessment. Each slide will be assessed by 3 independent primary screeners giving a total of 15,000 slide assessments. |
Project Protocol: |
Project protocol (pdf format, 115 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1600 |
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