Personal view. Is it reality or an illusion that liquid‐based cytology is better than conventional cervical smears?

Liquid-based cytology (LBC) has been heralded as the way forward for cervical screening, and as the answer to many of its problems. It is already used as a sole method of cell preparation in many private clinics in the UK. It is being used for colposcopy smears in many NHS clinics and is now being piloted for primary screening in three screening centres in England, as well as one in Scotland and one in Wales. LBC has been welcomed as a new technology because it deals with the problem of specimen adequacy at source, removing responsibility for slide preparation and fixation from the clinician or nurse. It provides uniformly well-fixed preparations that are free of inflammatory exudate and blood, and seem easier to screen than conventional smears. There are many articles in the world literature suggesting that LBC is more accurate than conventional screening, and it is thought likely to reduce the number of false negative tests. The main reasons for piloting LBC in the NHS Cervical Screening Programme (NHSCSP) lie in its potential for reducing screening times and for reducing the numbers of repeats for inadequate tests. LBC is expensive in terms of equipment, capital costs, maintenance, consumables, training, technical preparation time, transportation and disposal of liquid media. Its costs could be justified if they were offset by the money saved from reduced screening time and repeat tests, but only if its accuracy in terms of sensitivity and specificity were proven to be equal to or better than conventional cytology. Although that is generally held to be true by the public and medical profession alike, there is very little hard evidence to support it.     

Significance of atypia in conventional Papanicolaou smears and liquid-based cytology: a follow-up study

The diagnosis of atypical squamous epithelial cells, borderline nuclear changes, is associated with some controversy, as it encompasses benign, reactive, as well as possible neoplastic conditions. The aim of this study was to evaluate the follow-up diagnoses of cytological atypia in conventional Papanicolaou smears (CP) and liquid-based samples by the ThinPrep Pap Test (TP). A total of 1607 CP smears from 1 January 2000 to 31 December 2000 and 798 TP samples from 1 January 2002 to 31 December 2002 diagnosed as atypia were included. The results show that the detection rate of atypia in cervical cytological samples was reduced by 41.3% (P < 0.001) in TP compared with CP. Cytological and histological follow-up data showed the presence of neoplastic lesions in 34.7% of patients screened by TP versus 22.3% of patients screened by CP, corresponding to a 55.6% increase in TP (P < 0.001). Follow-up diagnosis of mild dysplasia was seen more than twice as often in TP than in CP (12.8% versus 5.0%, P < 0.001). The prevalence of moderate and severe dysplasia was significantly increased with 26.7% in TP compared with CP (21.9% versus 17.2%, P < 0.01). In conclusion, the ThinPrep Pap Test yielded a significant decrease in atypia rates compared with the conventional Papanicolaou test. In subsequent follow-up the percentage of neoplastic lesions was significantly increased in the ThinPrep Pap Test samples.     

Implementation of liquid-based cytology in the screening programme against cervical cancer in the County of Funen, Denmark, and status for the first year

As one of the first laboratories in Denmark (and Scandinavia), we have gradually implemented liquid-based cytology into the screening programme against cervical cancer in the County of Funen since 1 June 2001. This paper describes the course of the implementation period in the different steps in the screening programme, and the preliminary results obtained after the first year. We conclude that the new technique has improved the specimen and diagnostic quality. As a result of the reduction of the screening time, the workload in the laboratory is in balance although we have introduced a rapid review as a quality control. Besides, the reduction in the number of repeated cytological tests and follow-up visits at the gynaecologist means a saving for the screening programme as a whole. From our point of view the implementation of ThinPrep method is economically neutral.     

Quality procedures in non-gynaecological cytology laboratories in England and Wales

All non-gynaecological cytology laboratories in England and Wales (n = 212) were surveyed by telephone. The aim was to investigate what concepts of quality applied in this context and to establish what tools and techniques of quality improvement were used. The overall response was 146 (69%). The respondents mainly comprised NHS Trusts and University Departments. The study showed that there was a diverse approach to quality. All types of quality assurance and customer focus procedure questioned were undertaken but to a varied extent; three laboratories (2%) used a complete range and three (2%) used no procedure at all. Accreditation was associated with staffing adequacy and use of surveys, but not quality assurance (QA) or user focus. Laboratories with a high priority for quality performed more QA and reported a higher staffing adequacy. Critical incident analysis was dependent on workload. Computerization did not affect quality procedures and involvement in the Breast Screening Programme did not result in different quality measures. The time since last update was independent of all factors and external quality assurance (EQA) was not widely available. The study suggested that an integrated approach to quality had not been adopted in English and Welsh cytology laboratories and that there may be a need for a more strategic approach with greater availability of EQA, guidelines on quality tools, closer linkage of accreditation and quality procedures and the production of minimum and ideal standards. The ideal standard could be the complete range of procedures, and the minimum standard could comprise those processes in most frequent use, i.e. critical incident analysis, correlation methods, action on information, analysis of what is done with diagnostic information, a complaints procedure and customer surveys.     

The evaluation of human papillomavirus genotyping in cervical liquid-based cytology specimens; using the Roche Linear Array HPV genotyping assay

Objective:  To ascertain the usefulness of the Roche Linear Array human papillomavirus (HPV) genotyping assay for assessing HPV genotypes in liquid-based cytology (LBC) samples and to evaluate this methodology within a cytopathology laboratory. These tests are of importance as persistent infection with high-risk HPV genotypes is considered a causal factor in the development of cervical cancer.
Methods:  A total of 175 cervical LBC samples were tested using the Roche Linear Array HPV genotyping test. The suitability of the assay use in routine cytopathology laboratory was considered. HPV genotypes were matched to the cervical cytology results, which included negative, borderline nuclear abnormalities, mild, moderate and severe dyskaryosis.
Results:  The assay could be applied to screening samples with the combined result available at the reporting stage. There were no test failures. All samples used after cytological analysis had sufficient DNA for testing. The results were reproducible and easily read and there was concordance of results between biomedical scientists. The results of the assay showed co-infection with multiple HPV genotypes was common in both high-grade and low-grade cytology samples. The percentage of HPV+ samples in the normal cytology samples (although in this grouping the number of samples was low) was 37%. In the cytology samples reported as severe dyskaryosis the HPV genotypes most commonly found were HPV16 and HPV51.
Conclusion:  The assay was able to detect multiple HPV infection with a wide range of genotypes in LBC samples sent for routine cytological analysis. It would be suitable for use in a cytopathology laboratory. The results of the assay show that the genotype profile has some variation from other geographical regions, and more work is needed to determine population prevalence, to ascertain the impact of the HPV vaccine, to evaluate test for cure and HPV triage management.     

薄层液基细胞学检查在宫颈普查中应用的临床分析

目的：评价薄层液基细胞学检查在宫颈普查中应用的临床价值。方法：选择经薄层液基细胞学门诊普查妇女520例,其中经TCT检查结果提示ASCUS以上的妇女76例,均进一步采取阴道镜下宫颈活检病理检查,将TCT检查结果与阴道镜下宫颈活检病理检查结果对比分析。结果：TCT检查结果具有较高的检出率及符合率,HSIL组、SCC组与LSIL组符合率比较,差异具有统计学意义（P〈0.05）。结论：TCT检查作为妇科宫颈普查的方法,具有检出率及符合率高的优点;检查结果为HSIL或SCC时,应引起临床极高度重视。     

Transformation zone sampling rate is a useful performance indicator for practitioners collecting cervical samples using SurePathTM liquid-based cytology system

An analysis of the reports of 53 982 liquid-based cytology (LBC) samples processed at the Royal Victoria Infirmary, Newcastle, reveals a significant relationship between the transformation zone (TZ) sampling rate observed in specimens submitted from different practices and their overall detection rate for dyskaryosis. The observed correlation (R = 0.184; P = 0.033, CI = 0.017 to 0.397) is very similar to that described previously using conventional cervical smears and confirms the potential relevance of TZ sampling rates as an indicator of consistently effective specimen collection. The correlation between unsatisfactory sample rates and detection rates for high-grade dyskaryosis (R = -0.188, P = 0.030, CI = -0.865 to -0.045) also shows a significant relationship for LBC samples which was not previously seen in conventional smears. The essential role of smear taker feedback, the use of transformation zone sampling and unsatisfactory smear rates as key indicators and the practical issues relating to routine reporting of transformation zone components are discussed.     

薄层液基细胞学检查在宫颈普查中应用的临床分析

目的:评价薄层液基细胞学检查在宫颈普查中应用的临床价值。方法:选择经薄层液基细胞学门诊普查妇女520例,其中经TCT检查结果提示ASCUS以上的妇女76例,均进一步采取阴道镜下宫颈活检病理检查,将TCT检查结果与阴道镜下宫颈活检病理检查结果对比分析。结果:TCT检查结果具有较高的检出率及符合率,HSIL组、SCC组与LSIL组符合率比较,差异具有统计学意义(P<0.05)。结论:TCT检查作为妇科宫颈普查的方法,具有检出率及符合率高的优点;检查结果为HSIL或SCC时,应引起临床极高度重视。     

Cytopathology in France.

In France, organization of the cytopathology seems to be quite different from that specifically regulated in the USA and in some other European countries. The aim of this article is to underline these specificities and to describe the solutions we advocate concerning new technologies, teaching, quality assurance, national guidelines em leader, to make our current practice compatible with the international recommendations. Moreover, we highlight the peculiar status of French cytotechnologists' and comment on the recent dramatic decrease of the medical demography in France, the consequence of which may promote a controlled transfer of competence.     

Liquid‐based cytology: is this the way forward for cervical screening?

Liquid-based cytology (LBC) is currently being marketed as an alternative methodology to replace the conventional PAP smear in cervical cytology. A substantial body of literature exists in support of LBC, some of which is at least partially sponsored by product manufacturers. The majority of published literature in support of LBC employs Bethesda reporting terminology. In this study we have analysed published raw data and presented this in NHSCSP terminology. Claims relating to sensitivity, specificity and smear adequacy have then been considered with reference to this data. Our analysis of existing data does not support the nationwide implementation of LBC at present. Further studies are recommended in order to evaluate the place of this technology within the NHSCSP.     

Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia

A. Repše‐Fokter, A. Pogačnik, V. Snoj, M. Primic‐Žakelj and M. S. Fležar
Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia Objective: The purpose of the study was to perform a national review of negative, low‐grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. Methods: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high‐grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low‐grade, atypical or inadequate smear 1–40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. Results: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty‐one of 37 women also had high‐grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high‐grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno‐ and adenosquamous carcinomas (5/24, P < 0.05). Conclusion: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under‐diagnosed smears were not related to cancer stage or last cytology report before diagnosis.     

Should the laboratory assess the sampling adequacy of cervical smears?

Should the laboratory assess the sampling adequacy of cervical smears? The results of a questionnaire answered by 14 out of the 18 NHS laboratories in Scotland reporting cervical smears showed that, since the publication of Guidelines for Judging the Adequacy of a Cervical Smear, by the British Society for Clinical Cytology (BSCC), rates of unsatisfactory smears had risen from a mean of 3.3% to 6.5%, with some laboratories reporting rates of over 10%. Four laboratories followed the guidelines closely in requiring the presence of two indicators of sampling of the transformation zone, i.e. endocervical cells, metaplastic cells or endocervical mucus. Seven laboratories required one indicator either in all smears or in a subset, whilst three did not require any indicator at all. The laboratories observing the guidelines closely had a higher mean unsatisfactory rate than those partially observing them. The main impediment to the full implementation of the BSCC guidelines appeared to be fear of an unmanageably high unsatisfactory smear rate. The accuracy of the assessment of adequacy is questioned, as is the cost effectiveness of doing so.     

BSCC,Bethesda or other? Terminology in cervical cytology European panel discussion

The European panel agreed that reproducibility and translatability of terminology in cervical cytology were essential, arguing well for harmonization of reporting systems. The majority at this meeting use a modification of the Bethesda system (BS). Local modifications involved reporting subcategories within high grade and low grade lesions, which would not alter the overall translatability of their systems both with each other and BS. The majority agree that low grade lesions with and without koilocytosis should be managed similarly as should high grade lesions (moderate dysplasia/CIN2 or worse). Those systems linking moderate dysplasia with mild rather than severe dysplasia would need to define moderate dysplasia as such, if their results were to be translatable, which would be preferable to their using a different definition of low grade and high grade lesions. Translation between systems might anyway be facilitated by reporting moderate dysplasia as a subcategory within high grade, which was favoured by most of those present. Therefore, there is no need for exact agreement of terminology if broad principles are agreed. This useful discussion adds weight to the British Society for Clinical Cytology recommendation that the new classification should be adopted by the UK National Health Service Cervical Screening Programme. If the new classification is adopted, the UK would join the European consensus opinion on terminology.     

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories

OBJECTIVE: Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid-based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates. METHODS: Two National Health Service cytology laboratories in Manchester and Stockport were partially converted to the LBC ThinPrep process for a cervical screening trial. Three 1-week timing surveys were conducted over 7 months. The surveys covered all LBC-trained staff. The first survey in Manchester also covered staff undertaking conventional Pap screening. The smear readers used timers to record time taken for examining and reporting each slide. RESULTS: In Manchester, in the first survey, nearly 1 minute per slide was saved by the LBC method during primary microscopy. In both laboratories, the mean microscopy time for primary screening of LBC slides was reduced by almost 1 minute between the first and second surveys. There was no difference between the second and third surveys. Microscopy by cytopathologists was also 1 minute per slide quicker with LBC than conventional Pap. The LBC inadequate rates for both laboratories were <2.0%. Organizational factors impacted on the hourly LBC primary screening rates in the laboratories, the rate for Stockport being higher than the rates in the pilot evaluations. CONCLUSIONS: The timing surveys confirm that the LBC ThinPrep technology can improve laboratory efficiency. However, decision-makers should also consider the overall costs and benefits of introducing the technology in screening programmes, including the capital investment and workforce implications.     

Technical External Quality Assessment for SurePath® stained liquid-based cytology gynaecological cervical samples using control material – a novel approach

Aims and objective: The Technical External Quality Assessment Scheme (TEQA) introduced in Wales is based on NHSCSP publication No 19 [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology] which sets out the policies and standard operating procedures for the TEQA of Papanicolaou staining of gynaecological cervical samples. As part of a development plan for the TEQA scheme in Wales, the use of a control sample was introduced to the assessment process – a common control sample can provide a consistent assessment parameter independent of the recommended slide selection process [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology, NHSCSP Publication No 19, February 2004] enabling direct comparison of staining standards for laboratories within the region; this counters selection variation bias, establishing a process that may be more representative of routine staining results. Methods: A cervical sample was selected in line with the criteria described in publication 19 [External Quality Assessment Scheme for the Evaluation of Papanicolaou Staining in Cervical Cytology, NHSCSP Publication No 19, February 2004]. Thirteen slides were prepared by the scheme facilitator from this anonymized sample. These control slides were subsequently ‘fixed’ but not stained, then distributed to the laboratories participating in the TEQA scheme. The slides were stained using their standard regime, then returned to the facilitator for assessment. The slides showed consistent staining with no significant inter‐laboratory variation, however, the eosinophilic stained components exhibited an artificial colouration, which slightly altered the expected stained appearance; this was thought to be due to ‘cross‐reactivity’ of the spray fixative with the preserving agent. To address this artefact, a further development of control procedures was devised utilizing a pooled control sample procedure. Residual material from a number of similar samples was pooled and distributed in aliquots to participant laboratories for standard processing and staining; the completed slides were returned to the scheme facilitator for assessment. Results: The pooled sample slides were assessed at the next scheduled quarterly TEQA assessment. The overall scoring for these samples produced an acceptable level of Papanicolaou staining for 12 of the laboratories – only one laboratory produced a marginal score. The artefactual presentation of eosinophilia was not seen. Discussion/conclusion: This method of producing control material establishes consistency in the TEQA comparative assessment process, counters selection bias and reduces the time demands associated with slide selection. It may also prove useful in identifying technical problems within laboratories during sample preparation prior to or during staining, including equipment or process faults. This technique is now well established locally as an enhancement of the current TEQA scheme for the assessment of slide staining. We feel that this enhancement could be incorporated as a new initiative in the current National TEQA scheme as a complement to the established selection process.