Performance indicators of organized cervical screening in Romagna (Italy).

The availability of published data from organized cervical screening programmes in southern Europe is scant. In the Italian area of Romagna, a first round of organized screening (based on a 3-yearly Pap smear for women aged 25-64 years) was initiated between December 1995 and January 1997 and was completed in an average of 42 months (range 36-48 months). The target population included 305 478 women. Of these, 253 949 were eligible and received a personal letter of invitation. Age-specific screening performance indicators were calculated according to standard methods. The response rate within 6 months of invitation was 49.1% (n=124 621). The total participation rate including women who presented later was 61.7% (n=156 735). The recall rate was 35.2 per 1000 of participants (n=5514). Positive cytology results were distributed as follows: atypical squamous cells of un-determined significance/atypical glandular cells of undetermined significance (ASCUS/AGUS) 40.1%, low-grade squamous intraepithelial neoplasia (LGSIL) 48.6%, high-grade squamous intraepithelial neoplasia (HGSIL) 10.7% and carcinoma 0.7%. Compliance to colposcopy follow-up was 93.4% (n=5149). The biopsy rate was 52.4% (n=2696) of patients undergoing colposcopy. The detection rate was 4.5 per 1000 of participants (n=707) for CIN2-3 and 0.5 (n=75) for invasive carcinoma. The proportion of microinvasive carcinomas was 36.0% (n=27). The positive predictive value for CIN2-3/carcinoma was 5.8% for the cytology reports of ASCUS/AGUS, 7.6% for those of LGSIL, 76.5% for those of HGSIL, and 100.0% for those of carcinoma (80.4% for combined HGSIL/carcinoma). The ratio of observed to expected (or prevalent to incident) cases of invasive carcinoma was 2.35 (95% confidence interval (CI) 1.85-2.95). In conclusion, most early results of the programme were compatible with an acceptable performance.

Is it possible to define a better ASCUS class in cervicovaginal screening? A review of 187 cases.

OBJECTIVE: To try to better define the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) in a cervical screening protocol. STUDY DESIGN: Smears from 187 patients with cytologic diagnoses of ASCUS and histologic or two years' cytologic/colposcopic follow-up were reviewed. When an ASCUS diagnosis was confirmed, it was done strictly on the basis of the morphologic criteria recommended by the Regione Emilia Romagna Screening Protocol in 1997, trying also to subclassify ASCUS into favor reactive or favor neoplasia. RESULTS: Seventy ASCUS cases were negative (37.4%). Three cases (1.6%) were low grade squamous intraepithelial lesion, and seven (3.8%) were high grade squamous intraepithelial lesion. One hundred seven ASCUS cases (57.2%) were confirmed. Among the 70 negative cases, 36 (51.4%) had reactive changes on biopsy, 30 (42.9%) koilocytosis, 3 cervical intraepithelial neoplasia (CIN 1) and one CIN not otherwise specified (5.7% total). CONCLUSION: Reclassification of ASCUS cases using tighter criteria reduced them to a rate of 57.2% but missed 30 patients with histologic diagnoses of koilocytosis and 4 with histologic diagnoses of CIN.

Probability of early repeat Pap smear in an integrated cervical screening programme.

The integration of routine Pap smear practice based on self-referral into an organized programme based on personal invitation is the recommended approach to cervical cancer screening. In this study, the cytology archive of the integrated cervical screening programme implemented in the Faenza district (northern Italy) was used to compare the population of women responding to invitation with that of self-referred women for the cumulative probability of early (< 36 months) repeat Pap smear after a negative result. Between 1995 and 1998, women aged 25-64 living in five municipalities of the district were targeted by the first round of the programme. Eligible for the study were 2356 women responding to invitation for screening and 2221 women not invited because of self-referral for Pap smear at any other setting. The probability of early repeat Pap smear was estimated by the life table method. Differences were evaluated by the Gehan test. Multivariate determinants were assessed by the Cox regression analysis. At 36 months' follow-up, the cumulative probability of early repeat Pap smear was 44% among self-referred women and 6% among women responding to invitation (relative hazard = 4.8). For self-referred women, the probability was related to age (with a peak at 35-44 years), previous Pap smear history and municipality of residence. Among women responding to invitation, only an inverse association with age was demonstrated. In conclusion, the observed differences in overall probability and determinants of early repeat Pap smear between the two screening populations provided important information on Pap smear usage in the total target population.

Effects of the Bethesda System on the rate of unsatisfactory Pap smears in spontaneous cervical screening.

AIMS: In 1990, The Bethesda System (TBS) was introduced into spontaneous cervical screening practice in Ravenna, Italy. Negative/benign reports with the recommendation for early repeat smears (RERS) due to some limitation in sample adequacy were considered no longer acceptable. A monitoring program for the rate of unsatisfactory smears (UNS) was implemented. The aim of the present study was to evaluate the effects of such changes in the screening procedure. METHODS: The frequency of UNS in 1990 was compared with that of UNS+RERS in 1988 (assumed as a baseline year) by the calculation of the standardized rate ratio with the 95% confidence interval (CI). The trend in the standardized rate of UNS from 1990 to 1994 was evaluated by the calculation of the average annual variation with the 95% CI. RESULTS: The immediate effect of TBS (1990; 1988 comparison) was a significant increase in the rate of UNS attributable to scant cellularity, poor fixation and thick areas (rate ratio, 2.35; 95% CI, 2.18 to 2.53) and to the absence of endocervical component (1.45; 95% CI, 1.30 to 1.60). The rate of UNS attributable to the presence of cytolysis, inflammation, blood and foreign material decreased by about 6 times (0.16; 95% CI, 0.13 to 0.19). The midterm effect of TBS (trend from 1990 to 1994) was a decrease in the total rate of UNS by an average of 2.3% per year. The downward trend was significant for smears showing scant cellularity, poor fixation and thick areas (-1.5% per year) and the absence of endocervical component (-0.7% per year). UNS attributable to the presence of cytolysis, inflammation, blood and foreign material stabilized. CONCLUSIONS: TBS led to a substantial change in the type of information provided by the cytology report (immediate effect). The monitoring program according to TBS led to a reduction in UNS attributable to sample taker (midterm effect).

A feasibility study of ovarian cancer screening: does fine-needle aspiration improve ultrasound specificity?

AIMS AND BACKGROUND: The prognosis for ovarian cancer patients depends on the stage at diagnosis. As a prerequisite for any proposed procedure for ovarian cancer screening, high levels of specificity should be obtained using combinations of tests. Based on preliminary data from an ongoing feasibility study, this report is focused on the possible gain in specificity provided by fine-needle aspiration of occult ovarian masses detected by ultrasound. METHODS: Ultrasonography was used as a basic test, and fine-needle aspiration was obtained from selected patients. Those with (a) positive aspiration cytology or histology, (b) complex or solid masses showing volume increase, (c) complex or irregular masses and inadequate samples, and (d) recurrent cystic lesions were operated on. RESULTS: A total of 3541 asymptomatic patients 50-69 years of age underwent ultrasonography, and 98 were selected for fine-needle aspiration. Of these, 19 (positivity rate 19/3541 or 0.5%) were operated on. Two ovarian cancer cases (FIGO Stage II and III) were detected (detection rate 2/3541 or 0.6 x 1,000; positive predictive value 2/19 or 10.5%). Specificity was 3443/3539 or 97.3% for ultrasound alone and 3522/3539 or 99.5% for the procedure as a whole. Surgical exploration for relapses of benign cysts reduced by some 50% the potential gain in positive predictive value provided by aspiration cytology compared with ultrasound alone. CONCLUSIONS: Although fine-needle aspiration has improved the performance of ultrasound, this 2-level procedure does not appear to achieve acceptable levels of specificity.

Self-selection for mammography and breast cancer incidence by stage.

AIMS AND BACKGROUND: In the field of breast cancer control, obtaining population-based data on spontaneous mammography (MG) screening should be a priority. This study focuses on the breast cancer incidence and stage distribution in relation to MG use in Ravenna (Italy), 1987-88. METHODS: We estimated the MG rates, expected (E) incidence based on mortality data, observed (O) incidence, predicted excess incidence based on MG rates, observed excess incidence, and stage distribution according to the MG history. RESULTS: The highest MG rate (37%) was found among residents aged 40-44 but none of these had a T1a-bNO breast cancer diagnosed nor was the predicted excess incidence demonstrated. Between 45 and 64 years, 80% of self-selected screenees had repeat ("incidence") MG and the O:E incidence ratio was 1.32 (95% CI 1.09-1.58). The observed excess incidence was 3.8-fold (95% CI 2.56-5.16) greater than that predicted. Advanced (T2+ and/or N1+) cases accounted for 42% of patients diagnosed within 3 years of their last MG, for 55% of those diagnosed more than 3 years after their last MG, and for 70% of those with no previous MG. Above age 70, a significant worsening of stage at diagnosis was associated with a clearcut drop self-referral for MG. CONCLUSIONS: The results indicate that self-selection and its implications are major features of spontaneous screening practice.

Performance of fineneedle aspiration cytology of the breast. Clinical experience in Ravenna (Italy).

AIMS AND BACKGROUND: Fineneedle aspiration cytology (FNAC) is a routine test in the evaluation of breast lesions. We assessed the diagnostic accuracy of mammography (MG), physical examination (PE), ultrasonography (US) and FNAC in 1064 histologically confirmed breast lesions (638 malignant, 426 benign) observed consecutively at the Cancer Prevention Center of Ravenna (Italy). METHODS: The performance of each test and the additional contribution of FNAC were determined. RESULTS: FNAC was done in 69.6% of cancers and 39.7% of benign lesions (P = 0.00000), the frequency of aspiration being significantly associated with severity at MG, PE, and US. For FNAC, the true positive rate was 95.1% and the true negative rate 67.4%. Only one breast cancer case was detected by FNAC alone (additional true positive rate 0.2%). The positive predictive value of FNAC in the absence of other abnormalities was 5%. The negative predictive value of a benign report at MG, PE, US and FNAC was 100%. CONCLUSIONS: All breast lesions should be evaluated by all available techniques, especially FNAC, and open biopsy should be avoided for those reported as benign at all tests.

Apocrine cells in breast cyst fluid and their relationship to cyst type: a morphometric study.

The morphology of apocrine cells exfoliated in breast cyst fluid (BCF) was studied in 78 BCF samples obtained from 39 premenopausal patients with gross cystic disease who were bearing two simultaneously aspirated cysts. 57/78 samples showed cell clusters suitable for computer-assisted cytometry. This was performed on 5820 cells using a Leitz Texture Analysis System (TAS). We measured the surface areas of cytoplasm, nucleus and nucleolus; we also calculated the nuclear/cytoplasmic (N/C), nuclear/nucleolar (N/n) ratios and the nuclear roundness factor (RF). Cysts were divided according to the cationic pattern of BCF: Type I, K+/Na+ greater than 1.5; Type II, K+/Na+ less than 0.66. The cytometric analysis was made on 47 samples of Type I and 10 samples of Type II. At the light microscope, no difference was apparent between the apocrine cells coming from Type I or Type II cysts. Cytometric measurements showed significant differences for the apocrine cells aspirated from Type I vs. Type II cysts for the mean cytoplasmic area (97.13 +/- 24.28 S.D. mu2 vs. 59.66 +/- 14.90 S.D. mu2, respectively) and the mean nucleolar area (4.35 +/- 0.99 S.D. mu2 vs. 2.75 +/- 0.71 S.D. mu2, respectively). Our data do not allow the inference of apocrine changes in the epithelium lining the cysts simply from the cationic pattern of BCF. The significantly wider cytoplasm and nucleoli of the apocrine cells aspirated from Type I cysts could reflect different functional stages of these particular cells.