[Computerised monitoring of integrated cervical screening. Indicators of diagnostic performance]. / Monitoraggio informatizzato dello screening cervicale integrato. Indicatori di diagnosi.

In a previous issue of this journal, we presented the background, rationale, general methods, and indicators of participation of a computerised system for the monitoring of integrated cervical screening, i.e. the integration of spontaneous Pap smear practice into organised screening. We also reported the results of the application of those indicators in the general database of the Pathology Department of Imola Health District in northern Italy. In the current paper, we present the rationale and definitions of indicators of diagnostic performance (total Pap smears and rate of unsatisfactory Pap smears, distribution by cytology class reported, rate of patients without timely follow-up, detection rate, positive predictive value, distribution of cytology classes reported by histology diagnosis, and distribution of cases of CIN and carcinoma registered by detection modality) as well as the results of their application in the same database as above.

Cervical screening behavior of women with atypical squamous cells of undetermined significance (ASCUS).

Expectant follow-up based on early repeat Papanicolaou (Pap) smear(s) is the most commonly recommended management of patients with atypical squamous cells of undetermined significance (ASCUS). In a cervical cytology laboratory in northern Italy, a retrospective study of 1,087 ASCUS patients aged 25-64 was conducted. The primary aim was to assess the actual probability of early repeat Pap smear and associated factors. Univariate comparisons were based on the actuarial method. Multivariate associations were evaluated by Cox regression analysis. The cumulative probability of early repeat Pap smear was 0.11 at 6 mo, 0.29 at 12 mo, and 0.41 at 24 mo, with a multivariate association with screening sector (relative hazard, 3.0 for public offices and 2.8 for private offices vs. organized screening) and previous Pap smear history. Laboratory recommendation, patient age, place of birth, place of residence, marital status, and occupation exerted no independent effect. In conclusion, the probability of early repeat Pap smear was poor and independent of demographic and social factors. The frequency of follow-up failures emerged as a major problem with ASCUS management.

[An interlaboratory study of the use of PapNet in the quality control of cervico-vaginal cytology]. / Uno studio interlaboratorio sull'impiego di PapNet nel controllo di qualità della citologia cervico/vaginale.

In this feasibility study of the utilization of the PapNet System (Neuromedical Systems, Suffern, NY) for computer-assisted cervical/vaginal cytology diagnosis, a random sample of 329 negative smears and a series of 68 positive smears reported as such by the Caltagirone laboratory, underwent PapNet review at the Imola laboratory. False-positive (FP) cases (smears originally classified as ASCUS, LGSIL, AGUS, e HGSIL and interpreted as negative on PapNet) and false-negative (FN) cases (reverse discrepancies) were further and conventionally re-evaluated by the staff of the originating laboratory. On PapNet review, there were 16/68 FP cases (23.5%) e 20/329 FN cases (6.1%) with a FP:FN rate ratio of 3.8 (95% confidence interval, 2.2-6.3). At final re-examination of these diagnostic errors, most FP cases (14/16) were confirmed as such whereas the FN cases significantly decreased from 20 to 9, with a final rate of 2.7%. As a consequence, the ratio of the FP rate (14/68) to the FN rate (9/329) rose to 7.5 (4.1-12.6). The study suggests one potential approach to the preliminary utilization of PapNet by those laboratories that are interested in this technology. The results are in accordance with those of the previous PapNet review studies which have generally shown a greater frequency of FP cases compared with FN cases.

[The PAPNET system in the rescreening of negative cervical/vaginal smears. A study from the Imola cytology laboratory]. / Il sistema PAPNET nel rescreening degli strisci cervico/vaginali negativi. Uno studio del laboratorio di citologia di Imola.

The rescreening of negative cervical/vaginal smears is one of the potential areas of utilization of the systems for computer-assisted cytology diagnosis. In the Imola cytology laboratory, a random sample of 1309 conventionally prepared smears that had been originally reported as negative was rescreened with the PAPNET System (Neuromedical Systems, Inc., Suffern, NY). Smears with a PAPNET diagnosis other than negative were further and independently evaluated by the staff of the laboratory and classified according to the majority report. The PAPNET rescreening confirmed the original negative diagnosis for 1188 smears (907.6/1000) and led to the detection of 46 ASCUS/LGSIL cases (35.1/1000) and 2 AGUS/HGSIL cases (1.5/1000). Seventy-three smears (55.8/1000) were interpreted as unsatisfactory. The majority report confirmed the original negative diagnosis for 42 (91%) of the 46 PAPNET diagnoses of ASCUS/LGSIL and 50 (68%) of the 73 smears interpreted as unsatisfactory. The 2 cases of AGUS/HGSIL diagnosed by PAPNET were confirmed. The detection rate of ASCUS/LGSIL decreased from 35.1/1000 to 3.1/1000 (rate ratio 0.09, 95% confidence interval [95% CI] 0.02-0.22). The rate of unsatisfactory smears decreased from 55.8/1000 to 17.6/1000 (rate ratio 0.31, 95% CI 0.20-0.47). The rate of negative smears increased from 907.6/1000 to 977.9/1000 (rate ratio 1.08, 95% CI 1.02-1.14). In conclusion, the PAPNET rescreening of negative smears brought about a low detection rate of severe cellular changes. Though greater, the detection rate of low grade changes was substantially and significantly reduced by the majority reports. At our laboratory, the PAPNET rescreening does not appear to improve the performance of conventional cytodiagnosis.

Accuracy comparison between PAPNET diagnoses and conventional diagnoses in an Italian cervical cytology laboratory.

In a population-based cervical screening laboratory with a controlled workload, a retrospective PAPNET review of 1,654 Pap smears was performed. The series included a random sample of smears originally and conventionally classified as negative (no. 1,309) and unsatisfactory (no. 43), and 299 consecutive smears originally classified as abnormal. The PAPNET diagnoses and the original diagnoses were compared for accuracy. For smears with discordant classification, a majority diagnosis as obtained on manual review was used as a gold standard. The PAPNET testing showed a greater proportion of negative smears classified as unsatisfactory (3.7% vs. 0.2%; ratio, 16.7; 95% CI 12.4-22.0); a reduced proportion of ASCUS/LGSIL cases correctly identified as positive (i.e., a reduced sensitivity for such lesions) (76.3% vs. 97.9%; ratio, 0.78; 95% CI 0.66-0.91); an equal proportion (96.2%) of AGUS/HGSIL cases correctly identified as positive (i.e., an equal sensitivity for such lesions); and an equal proportion of negative smears correctly identified as such (i.e., an equal specificity). In conclusion, the PAPNET testing did not improve the diagnostic performance of the manual screening.

[Analysis of the intralaboratory diagnostic variability in the Imola cervical screening program]. / Analisi della variabilità diagnostica intralaboratorio nel programma di screening cervicale di Imola.

The value of the assessment of intralaboratory variability as a method for quality control of cervical screening is an ill-defined one. This model has been advocated and utilized by some Authors and only indirectly addressed by others. In Italy, only occasional studies have been published. The present analysis is part of a series of studies for the evaluation and quality control of the population cervical screening programme in the area of Imola. The agreement between the 5 cytologists was tested over a series of 150 smears selected from the routine material. The data were analyzed with the k statistic and the degree and direction of discrepancies were assessed by the percent distribution of paired diagnoses. The k values for agreement between the 10 possible pairs of cytologists varied between 0.25 and 0.49 (average value, 0.37). The indexes for agreement as based on three classes ('Negative'/ASCUS + LGSIL + HGSIL/'Unsatisfactory') varied from 0.35 to 0.56 (average value, 0.46). The cytologist-specific k values (as based on five classes) ranged from 0.29 to 0.43. For the observer with the lowest specific coefficient (designated as C4), the excess disagreement was restricted to the ASCUS class and the 'Unsatisfactory' notation. In particular, C4 diagnosed more often 'Negative' smears (74% vs. 44-55%) and less frequently ASCUS (11% vs. 22-31%) and 'Unsatisfactory' smears (3% vs. 6-11%). ASCUS was the least reproducible diagnosis (k = 0.22). The evaluation of the degree and direction of the diagnostic discrepancies between the five cytologists showed that the frequency of concordant diagnoses of ASCUS was as low as 39.7%. However, the discrepancies were almost always of one degree and were directed towards the 'Negative' class. Conversely, ASCUS was associated with considerable proportions of the 'Negative' diagnoses (17.3%) and those of LGSIL (31.8%). In the occasions when one observer interpreted a smear as 'Unsatisfactory' the paired diagnoses were almost evenly distributed among 'Unsatisfactory' (49.2%) and 'Negative' (43.0%). In absolute terms, the k coefficients in this study were compatible with moderate agreement. However, they were unfavourably influenced by the modalities for smear selection. The study specimens were selected by all cytologists from the routine material over a short time period and did not include smears interpretable as showing carcinoma. A comprehensive evaluation of the diagnostic performance of C4 showed that the disagreement with other cytologists was restricted to the diagnosis of ASCUS and the 'Unsatisfactory' notation and was accounted for by a lower frequency of such reports coupled with a greater frequency of the 'Negative' diagnoses. A conservative approach to lesions of minor significance is the most likely explanation for that pattern of disagreement. Although characterized by the poorest k value, the ASCUS diagnosis proved to be generally matched with reports of minor cytology changes. This was consistent with the formal definition for ASCUS in the original Bethesda System. The observation that the ASCUS diagnosis is applied to those changes is a prerequisite for a more conservative utilization of such report. In conclusion, the study revealed important correlates of the k coefficients and provided an encouraging picture of the cytologic substrates of the diagnosis of ASCUS.

[Ki-67 in carcinoma of the breast: from the frozen to the paraffin sections]. / Ki-67 nel carcinoma della mammella: dal congelato al paraffinato.

We have studied 49 breast cancers in order to evaluate the Ki-67 polyclonal antibody in immunohistochemical assessing of the proliferating cell index on paraffin embedded tissue sections. Polyclonal Ki-67 immunostaining has been compared with monoclonal Ki-67 immunostaining on frozen sections. This study has been performed on two groups of breast cancers: the first using a prospective method including 22 consecutive cases observed in 1994; the second one, in a retrospective analysis of 27 consecutive cases observed in 1987-1988. Frozen section have been shortly fixed with formalin, methanol and acetone and subsequently processed with Ki-67 monoclonal antibody. The paraffin sections, routinely fixed in formalin and embedded in paraffin, have been pretreated in a microwave oven before processing with Ki-67 polyclonal antibody. The proliferating cell index, expressed in a semi-quantitative evaluation as percentage of stained nuclei, resulted differently in the mean and in the median values between the frozen and the paraffin groups. The difference is bigger and significant in the retrospective group observed in 1987-88. On the contrary, the results obtained from frozen and paraffin sections of the prospective group observed in 1994 are comparable. The prospective and the retrospective groups significantly differ in the fixation time. In 1994 the specimens were fixed for no more than 36 hours while previously the fixation time wasn't standardized and often exceeded 36 hours. The Ki-67 polyclonal antibody on paraffin sections is comparable to the Ki-67 monoclonal antibody on frozen sections on condition that fixation is strikingly standardized. The immunostaining with vimentin as antigenicity preservation control is also advisable.