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.     

Using a quality control approach to define an 'adequately cellular' liquid-based cervical cytology specimen

Objective:  To define a minimum acceptable total squamous cellularity for (ThinPrep^®) liquid-based cervical cytology (LBC) specimens using quality control techniques.
Methods:  Two hundred LBC preparations were made containing varying numbers (<200) of severely dyskaryotic squamous cells and with varying total cellularities.
Results:  Ninety-eight per cent of the LBC preparations that were missed by one or more of three cytoscreeners had fewer than 16 abnormal objects (single dyskaryotic cells or clumps of cells) and 87 dyskaryotic cells. The minimum ratio of dyskaryotic to total squamous cells that, in a preparation of 5000 squamous cells has a probability of at least 0.98 that 87 or more dyskaryotic cells will be present is 1 : 47. Twenty-three preparations diagnosed as abnormal had ratios of dyskaryotic to total squamous cells of between 1 : 2.5 and 1 : 4596. There is thus no feasible minimum acceptable squamous cellularity that will give an acceptable probability of detection of all specimen vials containing abnormal cells in the observed proportions.
Conclusions:  It is suggested that the minimum acceptable cellularity for LBC specimens is set pragmatically by the screening programme to give a feasible percentage of repeat tests.     

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.     

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.     

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.     

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.     

Comparison of Cervical Cytology Reporting Rates: A Useful Adjunct to External Quality Assurance

Reporting rates for abnormal and inadequate cervical smears have been compared during a 5-year period in nine laboratories and related to targets and achievable ranges recently recommended by the National Health Service Cervical Screening Programme (NHSCSP). There was improved consistency in rates for all grades of abnormality as well as inadequate smears. the average rate for moderate and severe dyskaryosis combined increased to 1.6%, which is the target recommended by the NHSCSP, and the standard deviation fell from 0.52 to 0.27. Although average rates for mild dyskaryosis and borderline nuclear change combined and inadequate smears both remained within the achievable range recommended by the NHSCSP, four laboratories were above the upper limit for each of those categories in the final year. During the 5 years of the study there was a fall in the number of ‘inflammatory’smears coded as negative with a recommendation for early repeat. Only one laboratory still uses that category. the challenge for the future lies in controlling high rates for minor abnormalities and inadequate smears while maintaining acceptable rates for moderate and severe dyskaryosis. Comparison of reporting rates is regarded by the participating laboratories as a useful adjunct to external quality assurance. Les taux des frottis cervico-utérins anormaux et inadéquats ont été comparés sur une période de cinq ans pour neuf laboratoires et évalues par rapport aux objectifs et aux intervalles de valeur récemment publiés dans les recommandations du programme de dépistage cervico-utérin du NHS (NHSCSP). Une amélioration de l'homogenéïté des taux de tous les grades d'anomalies aussi bien que celui des frottis inadéquats a été observée. Les taux moyens de toutes les catégories ont augmentés. Le taux moyen de I'ensemble des dyscaryoses modérées et sévères, a augmenté pour atteindre 1,6%, ce qui est I'objectif recommandé par le NHSCSP, et I'ecart type est passé de 0,52 à 0,27. Bien que les taux moyens de l'ensemble des dyscaryoses légéres et des modifications nucléaires “borderline” (BNC) sgient restés dans l'intervalle recommandé par le NHSCSP, quatre laboratoires étaient audessus de la limite supérieure pour chacune de ces catégories, au cours de la derniére année. Au cours des cinq années de cette étude, il y a eu une chute du nombre des “frottis inflammatoires” codés comme négatifs mais où un contrôle rapproaché avait été recommandé. Un seul laboratoire utilise encore cette catégorie. Pour le futur, le challenge se situe au nivau du contrôle des taux élevés d'anomalies mineures et de frottis inadéquats tout en maintenant des taux acceptables de lésions de dyscaryoses moyennes à sévères. La comparaison des taux des différentes catégories de frottis est considérée comme une aide très utile pour I'assurance de qualité externe pour les différents laboratoires participants. Der Anteil abnormer und nicht verwertbarer Abstriche wurde über einen Zeitraum von fünf Jahren zwischen neun Labors und den Empfehlungen des National, Health Service Cervical Screening Programme (NHSCSP) verglichen. Es ergab sich eine bessere Übereinstimmung für alle Anomalien sowie die Rate nichtauswertbarer Abstriche. Der Anteil mässinger und schwerer Dysplasien zusammengefasst stieg auf 1,6% und entsprach damit der Vorgabe des NHSCSP. Die Standardab-weichung sank von 0,52 auf 0,27. Obgleich auch der Anteil der leichten Dysplasien und borderline-Fälle im Bereich der NHSCSP-Empfehlungen blieben lagen dennoch vier Labors auch im letzten Jahr oberhalb der Grenzwerte. Im Untersuchungszeitraum sank die Zahl der als enzündlich beurteilten und zur Kontrolle empfohlenen Fälle. Nur eines der Labors benützt diese Beurteilung noch. Die Forderung der Zukunft wird die Senkung der nichtauswertbaren Präparate und leichten Dysplasien unter Beibehaltung des Standards für mässige und schwere Dysplasien sein. Der Vergleich der Beurteilungen zwischen Labors wird als nützliche Ergänzung der externen Qualitätssicherung angesehen.     

Comparison of conventional Papanicolaou smear and SurePath® liquid-based cytology in the Copenhagen population screening programme for cervical cancer

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.     

Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology

A. Evered and N. Dudding Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology Objective: To evaluate virtual microscopy in terms of diagnostic performance and acceptability among practising cytologists. Methods: Twenty‐four experienced cytologists were recruited to examine 20 SurePath® cervical cytology slides by virtual microscopy. Diagnostic accuracy was compared with glass slide microscopy using an unbiased crossover experimental design. Responses were allocated a score of one for a correct identification of normal or abnormal (borderline/atypical changes in squamous or glandular cells or worse) and a score of zero for an incorrect response (a normal slide reported as abnormal or vice versa). Perceptions of virtual microscopy were assessed by questionnaire analysis. Results: Participants yielded a total of 285 responses for the virtual slide set and 300 for the glass slide set. The approximate time to screen a virtual slide was 18 minutes, compared with 8 minutes or less for a glass slide. Overall there was no significant difference between virtual microscopy and glass slide microscopy in terms of diagnostic accuracy (P = 0.22). Virtual microscopy under‐performed when images were captured over a narrow focal range (P = 0.01). Diagnostic accuracy of virtual microscopy equalled that of glass slide microscopy when participants were able to focus through the full thickness of the slide images (P = 0.07). The most common difficulties experienced by participants with virtual microscopy were freezing of the computer screen during image download, slow response of the computer during slide movement and, in some instances, ‘fuzzy’ images. Cytologists have a strong preference for glass slides over virtual microscopy despite the overall equal diagnostic performance of the two viewing modalities. Conclusions: Diagnostic accuracy of virtual microscopy can equal that of glass slide microscopy. However, without good computer network connections, wide focal range and software that permits effortless navigation across virtual slides, cytologists are unlikely to be convinced of the utility of this technology for cytology screening and diagnosis.     

Rapid rescreening of cervical smears as a quality control method in a high-risk population

OBJECTIVE: Cancer of the cervix is one of the commonest cancers in South Africa. Accurate cytological diagnosis is one of the prerequisites for an effective cervical screening programme and requires the implementation of appropriate quality assurance modalities. This study was undertaken to determine if rapid review of reportedly negative cervical smears is a useful internal quality assurance modality in an unscreened population with very high rates of cervical carcinoma. METHOD: Approximately 26% of all cervical smears received at the study institution between 1 January 1998 and 31 December 2003, and initially reported as negative or inadequate, underwent rapid review. RESULTS: A total of 62,866 (26%) cervical smears out of 241,796 reportedly negative or inadequate cervical smears underwent rapid review. An amended report was sent out in 373 (0.59%) of these 62,866 cervical smears. This included 101 cases of high-grade squamous intraepithelial lesion (HSIL) and high-grade atypical squamous cells (ASC-H), 143 low-grade squamous intraepithelial lesions, 54 atypical squamous cells of undetermined significance (ASC-US) and 33 atypical glandular cells that were not reported initially. The false-negative proportion for HSIL and ASC-H (combined) in this study was 5.76%. No squamous cell carcinomas were diagnosed on rapid review but one patient with HSIL/ASC-H on review had squamous cell carcinoma on biopsy. Three cytotechnologists had a lower sensitivity of primary screening and required retraining. CONCLUSIONS: Rapid review is beneficial as an internal quality assurance modality in an unscreened high-risk population and increases the detection of women with significant cervical lesions requiring treatment. The relatively low cost of rapid review compared with other rescreening modalities makes this an attractive option in low resource settings.     

An audit of the accuracy of fine needle aspiration using a liquid-based cytology system in the setting of a rapid access breast clinic

We have assessed the effectiveness and accuracy of reporting fine needle aspirates of the breast (FNAB) using a liquid-based cytology (LBC) system (the Cytospin) method) in the pressure situation of a rapid access clinic (RAC). We have reviewed every case from the RAC from June 1997 to February 2001 inclusive. There were 1322 cases, which accounted for 26% of the total FNAB received in our department over the period. There were 323 cancers and 999 benign cases in the group. The inadequate/nondiagnostic rate (C1) was 18%. The absolute sensitivity, including C1 cases, was 73% with the complete sensitivity being 90%. The groups of 'atypical, probably benign' (C3) and 'suspicious, probably malignant' (C4) accounted for a total of 6.2%. There were 28 false negative cases and 1 false positive case (a borderline phyllodes tumour). Comparing our results with the standards recommended by the NHSBSP has shown that the diagnosis of FNAB using this LBC method is feasible, accurate and reliable even in the pressure situation of a RAC.     

Breast fine needle aspiration cytology: a review of current practice in Australasia

M. C. Cummings, B. A. Waters and P. K. O’Rourke Breast fine needle aspiration cytology: a review of current practice in Australasia Aims: To investigate breast fine needle aspiration (FNA) cytology in Australasia, in terms of laboratory demographics, specimens received and quality control (QC). Methods: A questionnaire was sent to all laboratories enrolled in the FNA module of the Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program (QAP), requesting information about specimens received in a 3‐month period in 2001 and in 2008. Results: Responses were received from 81/180 laboratories in 2001 and from 94/200 in 2008. The mean number of cases per 3 months was 137 in 2001 and 141 in 2008 and for the 42 laboratories responding on both occasions, the mean number of cases declined from 191 to 149 (P = 0.001). The mean percentage of malignant cases was 11.7% in 2001 and 10.5% in 2008 and the mean percentages of unsatisfactory rates were 21.7% and 25.2%, respectively; 43.2% of laboratories in 2001 and 40.4% in 2008 reported fewer than 50 cases for the 3‐month period. The unsatisfactory rate was inversely proportional to the number of cases received. Most QC (69.1% in 2001, 71.3% in 2008) was carried out by correlation with any later histology. With no histology available, 35.8% of laboratories in 2001 and 48.9% in 2008 did no further follow‐up. Follow‐up of all diagnostic categories increased from 30.9% in 2001 to 44% in 2008. Conclusions: Breast FNA cytology is still actively undertaken in Australasia, but numbers have declined. Unsatisfactory rates have reached the Australian recommended upper limit and are inversely proportional to the total number of cases received. Overall QC measures are unchanged and consideration of a review of breast FNA guidelines is suggested.     

Rapid (partial) prescreening of cervical smears: the quality control method of choice?

Rapid rescreening of all negative and inadequate smears is the quality control method of choice in the UK. The sensitivity of primary screening of laboratory and individual screeners are major indicators of screening quality and are dependent on the number of false negative smears found by rapid screening for their calculation. High sensitivity may indicate good quality primary screening or poor quality rapid review. Quantifiably high quality rapid rescreening is essential if these sensitivity figures are to be meaningful. A 12-month study was undertaken in routine practice using the prescreening mode to ascertain the sensitivity of rapid (partial) screening in our department. The final results of smears were compared with those of rapid prescreening. The calculated sensitivity ranged from 92-54% for high-grade abnormalities and 75-33% for all grades, revealing a wide range of performance between individual prescreeners. Rapid prescreening can identify individuals best suited to rapid screening in routine practice. By using these prescreeners only, the sensitivity of cervical screening could be raised. Rapid (partial) prescreening should be considered as the quality control method of choice.     

Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance

AIM: To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. MATERIAL AND METHODS: The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RESULTS: RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. CONCLUSION: RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.     

Proposed Sheffield quantitative criteria in cervical cytology to assist the diagnosis and grading of squamous intra-epithelial lesions, as some Bethesda system definitions require amendment

Objective: This study assesses the accuracy of published quantitative and qualitative criteria in the Bethesda System (TBS) for squamous intra‐epithelial lesions. Methods: Quantitative image analysis was undertaken on illustrations from TBS publications and also from slides in Cytology Training Centre teaching sets. Comparisons were also made with the British Society for Clinical Cytology (BSCC) terminology in cervical cytology, using the illustrations in their terminology publication and amalgamating the results into their proposed new two‐tier model. Results: TBS quantitatively defines low‐grade squamous intra‐epithelial lesions (LSIL) in both conventional and liquid‐based cytology (LBC) preparations as showing nuclear enlargement more than ×3 the area of a normal intermediate squamous cell nucleus. This study found that the increase in mean nuclear area was limited to only ×2 in conventional preparations. In LBC (SurePath^TM) preparations, there was only a statistically non‐significant ×1.2 increase. This study identified a progressive and statistically significant reduction in mean cytoplasmic area from normal intermediate cells to LSIL and then to high‐grade squamous intra‐epithelial lesions (HSIL) in both conventional and LBC preparations. Furthermore, the most consistent quantitative finding in both conventional and LBC preparations was a statistically significant increase in the mean area and diameter ratios from normal intermediate cells to LSIL and then to HSIL. In all instances this varied from ×2 to just below ×3. This is in agreement with TBS, which states that the cytoplasmic area in HSIL is decreased leading to a marked increase in nuclear to cytoplasmic (NC) ratio. With the exception of an increase in mean nuclear area in conventional preparations from normal intermediate cells to LSIL, the predominant cause for this increase in NC ratios was a reduction in mean cytoplasmic area. The numerical increase in NC ratio for LSIL identified in this study was greater than implied by the ‘slightly increased’ statement in TBS. TBS comments that some HSIL cells can have the same degree of nuclear enlargement as in LSIL and that other HSIL cells may have much smaller nuclei than in LSIL. Both of these qualitative comments were supported in this study. The mean diameter NC ratios of 33% and 50% could provide useful diagnostic assistance in the distinction of normal intermediate cells and LSIL and between LSIL and HSIL, respectively. Because of overlapping individual ranges, however, additional diagnostic features such as nuclear morphology must be used in the distinction of normal intermediate cells, LSIL and HSIL. No statistical difference was identified in the mean diameter NC ratios between ASC‐US and LSIL in TBS publications. In addition, the proposed new BSCC low and high grades of squamous abnormality were not statistically different from ASC‐US/LSIL and HSIL, respectively. This provides support that the proposed BSCC two‐tier system of squamous abnormalities is comparable to TBS. This study shows that LBC has variable but major and significant effects on nuclear and cytoplasmic morphology and that quantitative definitions in conventional preparations cannot be automatically extrapolated to LBC methodology. Conclusions: The study shows that some TBS quantitative and qualitative criteria require amendment and that an alternative quantitative approach, such as diameter NC ratio has a more valid scientific evidence base. Furthermore, use of NC ratios avoids the problems associated with the variable changes in nuclear and cytoplasmic areas, occurring between conventional and different commercial LBC preparations. By contrast, classifications based on area comparisons must be tailored to the specific conventional or commercial LBC preparation.     

Use of the ThinPrep Imaging System for internal quality control of cervical cytology

T. Heard, A. Chandra, G. Culora, S.S. Gupta, A. Herbert and M. Morgan
Use of the ThinPrep Imaging System for internal quality control of cervical cytology Objective: To audit the use of the ThinPrep Imaging System (TIS) for internal quality control (IQC) in the place of rapid review (RR), and to compare its performance with routine primary screening. Method: During 9 months, 16 462 ThinPrep slides were processed by TIS. Slides were initially reviewed using the TIS review scope, as recommended by the manufacturer: 22 fields of view were observed and, if considered abnormal, a full microscopic review was conducted using the review scope. Different biomedical scientists (BMSs), working on each procedure in rotation, performed batches of TIS‐assisted quality control and routine primary screening independently on unmarked slides. Any slides with abnormalities detected by either method were referred to a consultant pathologist or advanced BMS practitioner for a final report. TIS results were compared with both previous records of RR and routine primary screening carried out on the same slides. We used the UK terminology in which ‘dyskaryosis’ is equivalent to squamous intraepithelial lesion (SIL) and borderline to atypical (including squamous and glandular cells). Results: TIS preview detected significantly more high‐grade dyskaryosis compared with RR during the previous 4 years: 2.0–4.2 compared with 0.1–1.8 detected per 1000 slides (P = 0.0001). TIS and routine screening were equivalent in sensitivity and specificity for the final cytology result, but BMSs were significantly more likely to classify slides as dyskaryotic rather than borderline when using TIS compared with routine screening. Referrals for potentially high‐grade abnormalities detected by TIS‐assisted IQC alone found 28 biopsies of at least cervical intraepithelial neoplasia grade 2 (CIN2+), whereas 15 CIN2+ biopsies were found on routine screening but missed using TIS. There was no significant change in the rates of inadequate tests, high‐ or low‐grade cytological abnormalities, or positive predictive value for CIN2+ when TIS was in use. Conclusions: Screening with TIS was more sensitive than RR for IQC, providing a rescreening method equivalent to routine primary screening in overall accuracy.     

Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations

A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp., Boxborough, MA) compared with current methodologies of cervical cytology in two high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and a genito-urinary medicine outpatient clinic were examined. The TP reported increased detection of all grades of dyskaryosis (mild, moderate and severe; + 4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of high-grade dyskaryosis (moderate or severe) were detected only using the TP, while an additional four cases classified as high-grade dyskaryosis with the TP were reported as borderline by our conventional methods. The split-study finding of increased sensitivity with the TP provides for improved clinical management of patients in our high-risk cohorts.     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

Retrospective study on performance of constancy check device in Linac beam monitoring using Statistical Process Control

AimTo examine the application of Statistical Process Control (SPC) and Ishikawa diagrams for retrospective evaluation of machine Quality Assurance (QA) performance in radiotherapyBackgroundSPC is a popular method for supplementing the performance of QA techniques in healthcare. This work investigates the applicability of SPC techniques and Ishikawa charts in machine QA.Materials and MethodsSPC has been applied to recommend QA limits on the particular beam parameters using the QUICKCHECK^webline QA portable constancy check device for 6 MV and 10 MV flattened photon beams from the Elekta Versa HD linear accelerator (Linac). Four machine QA parameters – beam flatness, beam symmetry along gun target direction and left-right direction, and beam quality factor (BQF) – were selected for retrospective analysis. Shewhart charts, Exponentially Weighted Moving Average (EWMA) charts and Cumulative Sum (CUSUM) charts were obtained for each parameter. The root causes for a failure in machine QA were broken down into an Ishikawa diagram enabling the user to identify the root cause of error and rectify the problem subsequently.ResultsShewhart charts and EWMA charts applied could detect loss in control in one variable in the 6 MV beams and in all four variables in 10 MV beams. CUSUM charts detected offsets in the readings. The Ishikawa chart exhaustively included the possible errors that lead to loss of control.ConclusionSPC is proven to be effective for detection of loss in control in machine QA. The Ishikawa chart provides the set of probable root causes of machine error useful while troubleshooting.     

Monitoring and evaluating the performance of the UK NHS Cervical Screening Programme: monitoring performance by using cytology outcomes adjusted for population characteristics

Current quality assurance measures used in the NHS cervical screening programme (NHSCSP) include a review of laboratories with percentages of moderate/severe and borderline/mild smear results outside the 10th-90th percentiles. The method is limited by the fact that many of these outlier smear percentages may reflect laboratories covering populations with low or high risk and/or short or long average screening intervals. This paper outlines a new approach to aid the detection of outlier laboratories, by using data collected at the primary care trust (PCT) or health authority (HA) level and making allowances for population characteristics and screening interval. The setting is the NHSCSP in England using annual data provided by HAs. Data from the screening year 2000-01 is used to illustrate the methodology, although the methods can also be applied to data at the PCT level (now being collected for 2002-03 onwards). Percentages of smear results have been analysed against a series of explanatory variables using logistic regression models. These explanatory variables include Townsend deprivation index, uptake-corrected ethnic minority composition, a measure of screening interval, area type and region. An expected percentage of borderline/mild and moderate/severe smears is estimated from the models and an observed : predicted ratio (OPRmod/sev and OPRbord/mild) calculated. Low values are suggestive of relative undercalling and high values overcalling, after allowance for population characteristics. Analysis of data for 2000-01 showed that the OPRmod/sev for the 99 HAs varied from 0.68 to 1.44. Laboratories with low percentages of moderate/severe smears, but associated with PCTs or HAs with OPRmod/sev values closer to unity may not need to be investigated as their observed rates are consistent with predicted rates based on population characteristics. The method could also be directly applied to laboratories if further information on the population covered by each laboratory were routinely collected.