Daily peer review of abnormal cervical smears in the assessment of individual practice as an additional method of internal quality control.

OBJECTIVE: An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. METHODS: Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance (ASC-US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. RESULTS: In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58-0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category-specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). CONCLUSION: In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists.

Clinical impact (cost-effectiveness) of qualifying atypical squamous cells of undeterminate significance (ASCUS) in cases favoring a reactive or dysplastic process.

The cost-effectiveness of qualifying ASCUS cases into two different subcategories, favoring a reactive (ASCUS-R) or dysplastic process (ASCUS-S), was evaluated at the Centro per lo Studio e la Prevenzione Oncologica of Florence in a prospective study. The study determined the positive predictive value (PPV) for histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2) or more (CIN>) severe lesion of the two ASCUS subgroups. ASCUS-S had a PPV (10.78%) comparable to low-grade squamous intraepithelial lesions (LSIL) (11.40%). For ASCUS-R cases, the recommendation of 6-mo repeat cytology prompting colposcopy in cases of persistent ASCUS or more severe cytology was also effective, as it selected a subgroup with a relatively high PPV (10.34%). The cost-effectiveness of a protocol based on ASCUS qualification was compared with two other possible options for nonqualified ASCUS cases: immediate colposcopy and colposcopy in persistent ASCUS at 6-mo repeat cytology. The detection rate of CIN2> was substantially higher using ASCUS qualification (35.9 vs 14.8 or 17.1). The cost per ASCUS subject was euro 24.99, 27.11, or 25.14 and that per CIN2> detected was euro 697, 1,831 or 1,470 for the three options, respectively. The evidence that ASCUS detection option implies a higher detection rate of CIN2> and subsequently a lower cost per CIN2> detection must be considered with caution and deserves confirmation by other comparative studies.

Interlaboratory reproducibility of the immunocytochemical assessment of oestrogen and progesterone receptors and proliferative activity in fine needle aspiration of breast cancer.

The purpose of this study was to establish the interlaboratory reproducibility of immunocytochemical analysis of oestrogen (ER) and progesterone (PR) expression and Mib1 growth fraction on fine needle aspiration (FNA) smears. A set of 44 immunostained slides for ER, PR and Mib1 were randomly selected from the archives of the Center for the Study and Prevention of Cancer (CSPO) of Florence, Italy, and submitted for reading to 6 Italian laboratories. The generalized kappa statistic was used as an indicator of agreement among the six laboratories. A good correlation for ER and PR was evident. For Mib1 the results showed some discrepancies. In addition to adequate standardization of procedures, these data confirm that the reliability of the immunocytochemistry is strictly linked to accurate analysis of the results.

Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirus testing.

Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57-132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93-88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72-82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening.

Analysis of the causes of false negative cytology reports on breast cancer fine needle aspirates.

Forty-six (2.9%) false negative reports were recorded among adequate fine needle aspirates from 1609 consecutive histologically proven carcinomas, observed from 1991 to 1993. False negatives were more frequent among younger women (< 40 years = 7.1; 40-49 years = 4.0; 50-59 years = 3.6; 60-69 years = 1.7; > 69 years = 1.5%), lobular invasive subtypes (5.4%), and smaller tumours (pT1a = 4.2; pT1b = 7.6; pT1c = 1.9; pT2 = 2.1; pT3-4 = 1.5%). The latter findings is probably ascribable to better differentiation and less precise sampling of small non-palpable tumours. No significant association was found between the false negative rate and the sampler's or reader's skill and experience. The former finding may be ascribed to the wide use of sonography guided aspiration, even for palpable masses, and the latter to the fact that readers were highly experienced and undergo periodic quality control of individual performance. False negatives were reclassified at reviews as true false negatives, reading errors or inadequates in 27, 11, and eight cases, respectively. The observed findings suggest that in most cases cytological faults were due to the absence of cytological atypia in cells sampled from well differentiated tumours, rather than to misinterpretation or sampling from adjacent normal tissues.