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.     

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England

R.G. Blanks
ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low‐grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.     

A study of the effect of introducing a restrictive cervical screening policy on laboratory workload and cervical cancer detection rates

This study examines the effect of a change in screening policy on the detection rate of severe dyskaryosis. During 1987 a total of 423 cases of severe dyskaryosis were identified by the Avon Screening Programme. Eleven per cent of these abnormal smears were repeat smears taken without clinical indication within the recommended 5 year recall period (interval smears). In a comparable control group of negative smears 31% were interval smears. Twenty-five per cent of the dyskaryotic interval smears (3% of the total severely dyskaryotic smears) were taken within 3 years of the previous negative smear, compared with 50% of the control group. By discouraging opportunistic smears within 5 years of the previous smear, the laboratory workload could be reduced by 30%, or within 3 years of the previous smear by 15%. There is, however, a risk of 11% and 3% respectively of missing a significant lesion (severe dyskaryosis).     

Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types

The causal relationship between persistent infection with high-risk HPV and cervical cancer has resulted in the development of HPV DNA detection systems. The widely used MY09/11 consensus PCR targets a 450bp conserved sequence in the HPV L1 gene, and can therefore amplify a broad spectrum of HPV types. However, limitations of these consensus primers are evident, particularly in regard to the variability in detection sensitivity among different HPV types. This study compared MY09/11 PCR with type-specific PCRs in the detection of oncogenic HPV types. The study population comprised 15, 774 patients. Consensus PCR failed to detect 522 (10.9%) HPV infections indicated by type-specific PCRs. A significant correlation between failure of consensus PCR and HPV type was found. HPV types 51, 68 and 45 were missed most frequently. The clinical relevance of the HPV infections missed by MY09/11 PCR was reflected in the fraction of cases with cytological abnormalities and in follow-up, showing 104 (25.4%) CIN2+ cases. The MY09/11 false negativity could be the result of poor sensitivity, mismatch of MY09/11 primers or disruption of L1 target by HPV integration or DNA degradation. Furthermore, MY09/11 PCR lacked specificity for oncogenic HPVs. Diagnostic accuracy of the PCR systems, in terms of sensitivity (MY09/11 PCR: 87.9%; type-specific PCRs: 98.3%) and specificity (MY09/11 PCR: 38.7%; type-specific PCRs: 76.14%), and predictive values for histologically confirmed CIN2+, suggest that type-specific PCRs could be used in a clinical setting as a reliable screening tool.     

Involving the General Practitioner In Screening For Cervical Cancer

In the Leiden region, the cervical cancer screening programme for the age group 35–54 years shifted in 1989 from one in which the smears were taken by specially trained paramedical personnel in health centres to a programme where the general practitioner is the smear taker. Hence, it is possible to compare the results of the two types of screening to evaluate whether involvement of general practitioners leads to better uptake of screening. In the 6 year period evaluated in this paper, the 3-yearly cytological rate per thousand for severe dysplasia or worse increased from 1.00 to 3.40; when stratified by age the positive rates were significantly higher. the histological rate per thousand for severe dysplasia increased from 0.60 to 2.09, and for carcinoma in situ from 0.35 to 1.36. All six invasive carcinomata were detected in the GP programme (0.31%). the general practitioner is clearly more able to attract the ‘high-risk’groups. Dans la reéion de Leiden, le programme de dépistage du cancer du col pour les tranches d'âge de 35–54 ans a été modifié en 1989. Le programme était initialement basé sur des frottis faits dans des centres de santé, par un personnel paramédical ayant suivi une formation particulière. Après 1989, le médecin généraliste est devenu le préleveur. II est done possible de comparer les résultats de ces 2 types de dépistage et d'apprécier si la participation des médecins généralistes a pour conséquence un meilleur dépistage. Au cours de la période d'étude, les taux pour 1000 de positivité cytologique pour les lésions graves (de type dysplasie sévère et plus) et par période de 3 ans ont augmenté de 1,00 à 3,40. Lorsque l'on stratifie sur l'âge, les taux de cas positifs sont significativement supérieurs. Le taux histologique des dysplasies sévères pour 1000 passe de 0,60 à 2,09 et celui du carcinome in situ de 0,35 à 1,36. Les 6 cas de carcinome invasif ont été détectés par le programme impliquant les médecins généralistes (0,31%). II est clair que le médecin généraliste est mieux placé pour dépister les patientes à“haut risque”. Im Bezirk von Leiden wurden die Abstriche der 35- bis 54 jährigen vor 1989 von speziell ausgebildeten Hilfskräften in Gesundheitszentren hergestellt, während diese Aufgabe dann von den Allgemeinmedizinern übernommen wurde. Dies erlaubt einen Vergleich zwische den Präparaten von zwei jeweils 3 Jahre umfassenden Perioden. Der Anteil schwerer Dysplasien und stärkerer Veränderungen nahm von 1.00 auf 3.40 pro Tausend zu. Der histologische Anteil der schweren Dysplasien erhöhte sich von 0.60 auf 2.09 und der der Carcinomata in situ von 0.35 auf 1.36. Alle 6 nachgewiesenen invasiven Carcinome wurden in den Abstrichen der Allgemeinmediziner entdeckt (0.31%_o). Damit ist klar, daß die Allgemeinmediziner die Risikogruppen besser zu erfassen vermögen.     

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.     

The development of the referral outcome diagram and an analysis of laboratory cancer detection rates in the English NHS cervical screening programme – is there an optimum level of detection of CIN 1 and CIN 2 lesions?

Objective: To use routine annual data from the English cervical screening laboratories (KC61 returns) to evaluate individual laboratory return characteristics with particular reference to factors associated with sensitivity and specificity. Methods: A graphical technique has been developed using data on referral to colposcopy and histological outcomes called a referral outcome (ROUT) diagram. The average grade of cervical intraepithelial neoplasia (CIN) detected (the mean CIN score, MCS) is plotted against the odds of a false‐positive referral. Further analysis has been conducted to examine the relationship between the MCS and screen‐detected invasive cancer rate. Results: There are large variations in ROUT diagram positions of individual laboratories and the diagram can be used to identify laboratories for further investigation. These variations are strongly influenced by substantial differences in the rate of low‐grade referrals and the MCS (and positive predictive value) are inversely related to the referral rate for low‐grade cytology (P < 0.001). There is a strong association between high MCS values and increased screen‐detected cancer rates (P < 0.001) particularly above an MCS of 2.2. The data can be re‐formulated in terms of CIN 2 and CIN 3 only where it can be shown that the invasive cancer rate rapidly increases if the numbers of CIN 2 lesions detected drops below 50% of the number of CIN 3 lesions. Given the complexity of cervical screening this may best be viewed as a hypothesis generating observation, best tested by interventional studies. Conclusions: The ROUT diagram represents a new and potentially interesting way of presenting annual return data. The national programme in England needs to balance the prevention of cancer against too many unnecessary referrals to colposcopy and the ROUT diagram, and associated data given in this paper may help toward this. Further research is required including examining the role of referral policy and threshold criteria in influencing low‐grade referrals and the relationship between MCS and cancer detection rate.     

Interlaboratory Reproducibility In Reporting Inadequate Cervical Smears—A Multicentre Multinational Study

A set of 300 vaginal smears was interpreted by 13 cytologists from six European laboratories, who were requested to report inadequate and suboptimal smears. the set had been appropriately seeded to reach approximately 10% inadequate and 20% suboptimal smear frequency. According to the majority report, 230 smears were classified as adequate (76.7%), 43 as inadequate (14.3%), and 27 as suboptimal (9.0%). Agreement with the majority report ranged from 52% to 91% (average 78%). Kappa statistics for reporting inadequate smears showed a high level of agreement for five cytologists, and fair to good agreement for eight. In contrast, K statistics for reporting suboptimal smears showed fair to good agreement with the majority report only in five instances, whereas agreement was poor for eight cytologists. ‘Inadequate smear’rates may be used to compare the quality of smears received in different laboratories, as there is a high level of agreement among cytologists as to what constitutes an inadequate smear. However, this is not true for ‘suboptimal smear’ rates, and more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears: more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears. Une série de 300 frottis cervico-vaginaux a été examinee par 13 cytologistes appartenant à 6 laboratoires européens auxquels il avait été demandé de signaler les frottis inadéquats et sub-optimaux. Cette série de frottis a été constituée de façon à atteindre approximativement une fréquence de 10% de frottis inadéquats et de 20% de frottis sub-optimaux. Si I'on considère les réponses faites par la majorité des cytologistes, 230 frottis ont été classés adéquats (76,7%), 43 classés inadéquats (14,3%), et 27 comme sub-optimaux (9,0%). La concordance avec les réponses de la majorité des cytologistes varie de 52%à 91% (moyenne 78%). Concernant le signalement des frottis inadéquats, le test Kappa est excellent pour 5 cytologistes et moyen à bon pour les 8 autres. Au contraire, pour le signalement des frottis sub-optimaux, le test Kappa montre un accord moyen à bon avec les réponses de la majorité seulement dans 5 cas alors que I'agrément est mauvais pour 8 cytologistes. La fréquence des frottis inadéquats peut être utilisée pour comparer la qualité de prélèvement du frottis dans différents laboratoires, alors que les comparaisons de la fréquence des frottis sub-optimaux sont discutables, du fait d'un biais de diagnostic évident. Des critéres plus précis pour le signalement des frottis sub-optimaux doivent étre définis et testés si cette catégorie doit être retenue pour rapporter les frottis de mauvaise qualité. 300 Abstriche wurden durch 13 Zytologen aus 6 europäischen Laboratorien hinsichtlich der Kriterien ‘unbrauchbar’und ‘suboptimal’beurteilt. Die Sammlung enthielt etwa 10% unbrauchbare und 20% suboptimale Präparate. Mehrheitlich wurden 230 Abstriche als auswertbar (76,7%), 43 als unbrauchbar (14,3%) und 27 als suboptimal (9,0%) bezeichnet. Die Statistik ergab hinsichtlich der unbrauchbaren Abstriche eine ausgezeichnete Ûbereinstimmung für 5 und eine gute Ûbereinstim-mung für 8 Zytologen. Demgegenüber zeigte sich hinsichtlich der Beurteilung suboptimal nur 5mal eine gute und 8mal eine schlechte Ûbereinstimmung. Damit ist die Kategorie suboptimal ungeeignet zum Vergleich und bedarf einer genaueren Definition wenn sie für die Qualitätskontrolle eingesetzt werden soll.     

Effect of regular 3-yearly screening on the incidence of cervical smears: the Leiden experience

The effect of regular 3-yearly screening over a period of 12 years, on the incidence of cervical cancer in 25,000 women aged 35-54 years, is examined. The rate of squamous cell carcinoma decreased from 0.38 per 1000 women in the first round to zero in the fourth round. Similarly, the rate of carcinoma in situ declined from 1.69 per 1000 women in the first round to 0.35 per 1000 in the fourth round. The rates of severe dysplasia showed no decline. Cytologic under diagnosis of carcinoma-in-situ and cervical carcinoma increased with each round. Widowed and divorced women and those living in urban areas were identified as high risk groups.     

Some Aspects of Cervical Screening In Southern New Zealand; the Situation Before Implementation of the National Cervical Cancer Prevention Programme

To gain some idea of cervical screening in Otago and Southland (two southern provinces of New Zealand), before the implementation of a national cervical cancer prevention programme, a questionnaire was sent to all doctors identified as smear takers. Questionnaires were returned by 75% of the doctors. Only 53.8% of practice nurses were involved in taking smears. Well Women Clinics staffed by nurses were not widespread in either province. Just under half (46.4%) of doctors took cervical smears as part of a health check programme. Sixty-three per cent (63.3%) routinely performed a pelvic examination when taking a smear. Surprisingly few doctors were familiar with the technique of placing spatula and cytobrush samples on one slide, a manoeuvre which could significantly reduce the workload of the cytology laboratories. Only a minority of doctors were aware of a new sampler which can provide samples equivalent to combined spatular-cytobrush smears. There was confusion over the timing of a repeat smear following two normal ones. the recommended interval of 3 years was only complied with by 44.2% of doctors. However, 71.4% of respondents did remind women to have smears. the study indicates that many doctors already provide patients with a good cervical screening service, and this augers well for the national screening programme. Afin d'abtenir des informations sur le dépistage du cancer du col utérin dans les provinces d'Otago et de Southland (2 provinces du sud de la Nouvelle Zélande), préalablement au lancement d'un programme de prévention, un questionnaire a été envoyéà tous les médecins susceptibles de réaliser des frottis. Ces questionnaires ont été renvoyés par 75% d'entre eux. Seulement 53.8% des infirmiéres sont concernées par la réalisation des frottis. Les ‘Well Women Clinics’dirigées par des infirmiéres ne sont pas très répandues dans ces deux provinces. Moins de la moitié des médecins (46.4%) font des frottis dans le cadre d'un programme de bilan de santé. Soixante trois pourcent (63.3%) font un examen pelvien systématique lorsqu'ils réalisent un frottis. De façon surprenante, peu de médecins sont familiarisés avec la technique de l'étalement sur une même lame de la spatule et de la cytobrush, technique qui réduit notable-ment le travail des laboratoires de cytologie. eule une minorité de médecins est au courant de l'existence de ce nouveau système permettant d'obtenir l'equivalent d'un frottis combinéà la spatule et à la cytobrush. Une confusion a été constatée à propos de l'intervalle recommandé après 2 frottis normaux. Les médecins se sont conformés à l'intervalle recommandé de 3 ans pour 44.2% d'entre eux. Cependant 71.4% des médecins répondeurs rappellent à leurs patientes qu'elles doivent faire pratiquer des frottis. Cette étude montre que de nombreux médecins proposent une bonne utilisation du dépistage du cancer du col à leurs patientes, signe de bonne augure pour le programme national de dépistage. Um die Lage hinsichtlich eines gynäkologischen Screenings in den beiden südlichen Provinzen von Neuseeland, Otago und Southland, zu erfassen, wurden Fragebogen an alle Ärzte verschickt von welchen bekannt wer, daß sie Abstriche herstellen. 75% der Fragebogen wurden beantwortet. Nur in 53.8% der Praxen waren die Schwestern mit der Herstellung der Abstriche betraut. In beiden Provinzen gab es kaum ‘Well Women Clinics’. Etwas weniger als die Hälfte (46.4%) der Ärzte fertigen Cervikalabstrich im Rahmen eines Gesundheitscheques an, 63% (63.3%) von diesen führte routinemäßig gleichzeitig eine Beckenuntersuchung durch. Überraschenderweise waren nur wenige Ärzte mit der Technik Spatel-und Cytobrushmaterial auf einem einzigen Objektträger aufzutragen vertraut, nur eine Minderheit kannte neue Verfahren, die dem kombinierten Spatel- und Cytobrushabstrich entsprechen. Es herrschte Unklarheit hinsichtlich der Kontrollzeiträume nach 2 normalen Abstrichen. Der empfohlene Zeitraum von 3 Jahren war nur 44.2% der Ärzte bekannt. Trotzdem forderten 71.4% die Patientinnen auf, Abstriche herstellen zu lassen. Die Studie zeigt, daß viele Ärzte ihre Patientinnen bereits mit einem guten Screeningprogramm versorgen und bietet somit gute Voraussetzungen für ein nationales Screeningprogramm.     

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations

The objective of this study was to estimate: (i) the sensitivity of cytologists in recognizing abnormal smears; (ii) the sensitivity of cervical cytology as a method of detecting abnormal smears among those obtained in the presence of cervical intraepithelial neoplasia (CIN). Study subjects were 61 women with a histologically confirmed CIN identified through colpohistological and cytologic screening. For objective (i) new smears were taken from study subjects just before treatment, mixed with routine preparations, interpreted by unaware cytologists and then blindly reviewed by a group of three expert supervisors, who reached a consensus diagnosis. Cytologists classified as positive for squamous intraepithelial lesion (SIL) 30 of the 34 smears judged as positive by supervisors (100% of smears classified as high-grade and 67% of smears classified as low-grade SIL by the supervisors). Our approach, based on creating a set of smears with a high a priori probability of being positive, proved to be an efficient way of estimating errors of interpretation. For objective (ii), smears taken at the moment of diagnosis, just before biopsy, were also reviewed by the same supervisors. These CIN cases were identified among asymptomatic women independently of cytological findings and results are therefore not subject to verification bias. Among the 33 histological CINII/III, four (12%) smears had no atypical cells (three negatives and one unsatisfactory) at review. The same proportion was 26% (four negatives and one unsatisfactory) among the 19 histological CINI. No significant differences in smear content were found between the seven ‘false negatives’ and a sample of ‘true positives’ and ‘true negatives’ for a number of formal adequacy criteria (including presence of endocervical cells). Strong differences were found between positive smears taken just before biopsy and those taken just before treatment (in 11 women the first smear only was positive, while the opposite was never observed), suggesting an effect of punch biopsy in removing lesions.     

The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme

Objective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women’s screening histories as episodes rather than as individual smears. Design: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. Setting: NHS Cervical Screening Programme. Population: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. Methods: Cytology information obtained from the call/recall (‘Exeter’) computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. Main outcome measures: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. Results: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20–24 years down to 0.9% in women aged 60–64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. Conclusion: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.     

Implications of gynaecological abnormalities in pre-selection criteria for cervical screening: preliminary evaluation of 3602 subjects in South India

Early detection and eradication of cervical cancer and its precursor lesions through organized mass cytological screening programmes have recently gained considerable attention in developing countries. Strategies for both cost saving and effective implementation are however required for mass cervical screening in developing countries. In an early cancer detection programme conducted in South India, we analysed cytological abnormalities in 3602 women and correlated the results with other factors, including age, gynaecological complaints, number of years of married life and parity to see if pre-selection for cytologic screening was possible. Only lower grades of dysplasia were found in asymptomatic women below the age of 40 years. In asymptomatic women, malignancy and higher grades of dysplasia were confined to women with a clinically abnormal cervix only. Univariate analysis also revealed that subjects with a parity of more than 3 and a married life of more than 20 years had a significantly higher number of cytological abnormalities. However, on a multivariate analysis the increased number of marital years was not found to be an independent variable. These results suggest that asymptomatic women below the age of 40 years with a married life of less than 20 years and parity below 3, may be excluded from screening campaigns, and that pre-selection for cytologic screening is possible by introducing a programme of clinical and speculum examination of the cervix.     

Interlaboratory reproducibility of atypical squamous cells of undetermined significance report: a national survey

The study was aimed at assessing interlaboratory reproducibility in the reporting of cervical smears in the atypical squamous cells of undetermined significance (ASCUS) category. A set of 50 selected slides circulated among 89 laboratories, currently involved in population-based screening programmes for cervical cancer, which provided a diagnostic report according to four main reporting categories based on the 1991 Bethesda system. Interlaboratory agreement was determined according to kappa (K) statistics: overall and weighted K values were determined for each laboratory and for single reporting categories. The results showed a very low reproducibility for the ASCUS category. This finding supports the Bethesda system 1991 recommendation to limit the use of this reporting category and suggests that the clinical response to ASCUS reports should be decided locally, based on the observed positive predictive value for cervical intraepithelial neoplasia 2 or more severe lesions.     

Cervical intraepithelial neoplasia grade III (CIN III) and invasive cervical carcinoma: the yawning gap revisited and the treatment of risk

In a 3-year study of the population of Southampton and south-west Hampshire there were 10 times as many cases of CIN III compared with invasive squamous carcinoma (700 compared with 70). The peak incidence of CIN III per 1000 screened women years was in those aged 25-29 years, which was 20 years earlier than the peak incidence of invasive cervical cancer per 1000 women years at risk. Ninety percent of CIN III was diagnosed in women under 50 years. There were 14 cases of cervical glandular intraepithelial neoplasia grade III (CGIN III), three coexisting with CIN III, all in women aged under 50 years: the gap between intraepithelial and invasive lesions was not seen for glandular neoplasia. Although referral was for at least moderate dyskaryosis in 86.8% of women with CIN III or CGIN III, most had been screened previously, either having had mild abnormalities requiring repeat cytology (39.8%) or negative cytology (34.5%). Only 12 women aged > or = 50 years had previous negative cytology: 21.4% compared with 35.6% of women aged < 50 years (P = 0.034). The results of this study suggest that the best opportunity for preventing invasive squamous cell carcinoma lies in screening women aged 20-39 years when the incidence of CIN III in the screened population is highest and before the peak incidence of invasive disease. The results also indicate the importance of repeated screening and follow up of minor cytological abnormalities in the detection of CIN III. The benefit of screening must be regarded as a treatment of risk, since it is almost certain that a high proportion of CIN III regresses or persists unchanged.     

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.     

Inadequate cervical cytology—the need to audit individual smear takers'' inadequate rates

In order to assess the performance of individual smear takers, their rates of inadequate smears, due to insufficient material, were monitored between 1992 and 1996. Although the yearly average clinic inadequate rates were all at acceptable levels, there was great variation of rates between smear takers, ranging from 0% to 19.5%. Identification of individuals with unacceptably high inadequate rates allowed them to undergo further training. Continuous monitoring of these inadequate rates can be used to measure levels of performance amongst all smear takers, but is particularly useful for new smear takers, or those who have required retraining.     

Evaluation of 100% rapid rescreening of negative cervical smears as a quality assurance measure

OBJECTIVE: The objective of this study was to compare the performance of 100% rapid rescreening, 10% random rescreening and the review of smears selected on the basis of clinical criteria, as a method of internal quality control of cervical smears classified as negative during routine screening. METHODS: A total of 3149 smears were analysed, 173 of which were classified as positive and 2887 as negative, while 89 smears were considered unsatisfactory. The smears classified as negative were submitted to 100% rapid rescreening, 10% random rescreening, and rescreening based on clinical criteria. The rescreening stages were blinded and results were classified according to the Bethesda 2001 terminology. Six cytologists participated in this study, two of whom were responsible for routine screening while the other four alternated in carrying out rescreening so that no individual reviewed the same slide more than once. RESULTS: The 100% rapid rescreening method identified 92 suspect smears, of which 42 were considered positive at final diagnosis. Of the 289 smears submitted to the 10% rescreening method, four were considered abnormal but only one was confirmed positive in the final diagnosis. Of the 690 smears rescreened on the basis of clinical criteria, 10 were considered abnormal and eight received a positive final diagnosis. CONCLUSIONS: The 100% rapid rescreening method is more efficient at detecting false-negative results than 10% random rescreening or rescreening on the basis of clinical criteria, and is recommended as an internal quality control method.