Five-year annual incidence and clinico-molecular features of breast cancer after the last negative screening mammography at age 68-69.

OBJECTIVE: The European Commission Initiative on Breast Cancer recommendation for triennial screening of women aged 70-74 is based on very weak evidence. A cohort of Italian women who had their last biennial screening mammography at age 68-69 was followed up for 5 years, assumed to represent the interval to another hypothetical screening mammography, in order to determine the annual proportional incidence of interval breast cancer. METHODS: The cohort included 118,370 women. They had their last mammography between 1997 and 2008. Incident breast cancers were identified by record-linking the cohort with the regional breast cancer registry. The expected incidence in the age range 65-74 was estimated with an age-period-cohort model. The number of interval cancers was divided by the expected number to obtain their proportional incidence. RESULTS: Overall, there were 298,658 woman-years at risk with 371 interval cancers versus 988.8 expected. In the first, second, third, fourth, and fifth interval year, the proportional incidence was 0.09 (95% confidence interval, 0.06-0.13), 0.32 (0.25-0.39), 0.60 (0.49-0.73), 0.75 (0.60-0.92), and 0.81 (0.60-1.07), respectively. Between the second and the fifth year, tumour stage and molecular subtype did not change significantly. CONCLUSION: Though not supported by these findings, the proposal of triennial screening for women aged 70-74 merits further research, because the 95% confidence interval of the third-year proportional incidence of interval cancer included 0.50-the maximum limit considered acceptable for women aged 50-69. KEY POINTS: • The third-year incidence of breast cancer relative to the expected one was 0.60 (95% confidence interval, 0.49-0.73). • Between the second and the fifth year, tumour stage and molecular subtype did not change significantly (p >0.10). • The proposal of a 3-year screening interval at age 70-74 merits further evaluation.

An online quality assurance program for colposcopy in a population-based cervical screening setting in Italy: results on colposcopic impression.

OBJECTIVE: To report the results of an Internet-based colposcopy quality assurance program from a population-based cervical screening service in a large region of northern Italy. METHODS: In 2010 to 2011, a Web application was made accessible on the Web site of the regional administration. Fifty-nine colposcopists of the registered 65 participated. They logged-in, viewed a posted set of 50 high-quality digital colpophotographs selected by an expert committee, and rated them for colposcopic impression using a 4-tier classification (Negative; abnormal, grade 1 [G1]; abnormal, grade 2 [G2]; suspected invasive cancer [Cancer]) derived from the International Federation for Cervical Pathology and Colposcopy 2002 classification. kappa (κ) coefficients for intercolposcopist agreement and colposcopist-committee agreement were calculated. RESULTS: Colposcopist-committee agreement was greater than intercolposcopist agreement (overall κ 0.69 vs 0.60, p<.001). The κ values for colposcopist-committee agreement were 0.83 on Negative, 0.53 on G1, 0.66 on G2, and 0.80 on Cancer (all p values for pairwise comparisons<.001, except for Negative vs Cancer [p=.078]). There was no systematic tendency for colposcopists to underestimate or overestimate the colposcopic findings (2-tailed sign test, p=.13). Overall colposcopist-committee agreement was greater among patients 35 years or older (p<.001) and for colposcopists with previous quality assurance experiences (p<.01). Only 0.2% of Negative impressions were formulated for a cervical intraepithelial neoplasia grade 2 or worse. As a parallel finding, the impression of Cancer predicted cervical intraepithelial neoplasia grade 2 or less in 0.5% of cases. The histologic substrates of G1 were dispersed over a large spectrum. CONCLUSIONS: The reproducibility of colposcopic impression, when classified by trained colposcopists examining high-quality images, is higher than is generally thought.

An image quality review programme in a population-based mammography screening service.

INTRODUCTION: Mammography is one of the most technically demanding radiographic processes, and mammography quality assurance initiatives are priorities in the implementation of public health screening services. In the optimisation of image quality (IQ), radiographers play a major role. Between 1998 and 2009, the steering committee for mammography of a large population-based screening service in northern Italy undertook several audit checks of the imaging facilities. In 2009, the target age range of the screening service was extended. The mammogram volume was projected to increase steeply but with no substantial increase in the radiographer workforce. METHODS: In view of the potential impact on mammographic IQ, the passive audit approach was abandoned in favour of an active radiographer-oriented IQ review programme. Its technical basis consists of regularly repeated rounds of review of random samples of digital mammograms performed by each first-level radiographer and by more experienced local reference radiographers, with IQ classification, followed by a training effort and a monitoring work. RESULTS: The mammogram volume grew from 140,822 in 2008 to 319,394 in 2014 (+127%) and then stabilised. In 2012, the proportion of mammograms with a poor IQ rose from 0.6% to 19.3%, paralleled by a substantial decrease of mammograms interpreted to have a moderate and perfect IQ. Conversely, a generalised improvement occurred in both rounds of 2016 and in the first round of 2018. CONCLUSION: In the new challenging scenario, the programme proved to be effective. A successful IQ review initiative is one that encourages radiographers to participate with a positive and confident attitude.

Incidence of interval breast cancer among women aged 45-49 in an organised mammography screening setting.

OBJECTIVE: To estimate the proportional incidence (PI) of first- and second-year interval breast cancer among women aged 45-49. METHODS: In the Emilia-Romagna Region (northern Italy), women aged 45-49 are invited to mammography screening annually, and women aged 50-74 biennially. For younger ones, the proportional incidence of interval cancer in the first and unique interval year was calculated using standard methods. For the second, hypothetical year, it was estimated using two different estimates of the ratio between the second- and the first-year proportional incidence observed among women aged 50-54. Overall, 567,151 negative mammography records were used. RESULTS: In the first interval year, the observed proportional incidence of interval cancer among women aged 45-49 was 0.27 (95% confidence interval (CI), 0.22-0.33), within the European limit considered desirable for women aged 50-69 (<0.30). In the second, hypothetical interval year, the estimated proportional incidence ranged from 0.61 (95% CI, 0.43-0.86) to 0.48 (95% CI, 0.31-0.76) depending on whether the estimate was based on data from the pre-digital or digital era, respectively. CONCLUSION: The more up-to-date estimate of 0.48, slightly below the maximum limit considered acceptable for women aged 50-69 (<0.50), suggests that a screening interval of two years may also be an acceptable option for women aged 45-49.

Incidence, detection, and tumour stage of breast cancer in a cohort of Italian women with negative screening mammography report recommending early (short-interval) rescreen.

BACKGROUND: Although poorly described in the literature, the practice of early (short-interval) rescreen after a negative screening mammogram is controversial due to its financial and psychological burden and because it is of no proven benefit. METHODS: The present study targeted an Italian 2-yearly screening programme (Emilia-Romagna Region, 1997-2002). An electronic dataset of 647,876 eligible negative mammography records from 376,257 women aged 50-69 years was record-linked with the regional breast cancer registry. The statistical analysis addressed the following research questions: (1) the prevalence of recommendation for early (<24 months) rescreen (RES) among negative mammography reports; (2) factors associated with the likelihood of a women receiving RES; and (3) whether women receiving RES and women receiving standard negative reports differed in terms of proportional incidence of interval breast cancer, recall rate at the next rescreen, detection rate of breast cancer at the next rescreen and the odds of having late-stage breast cancer during the interscreening interval and at the next rescreen. RESULTS: RES was used in eight out of 13 screening centres, where it was found in 4171 out of 313,320 negative reports (average rate 1.33%; range 0.05%-4.33%). Reports with RES were more likely for women aged 50-59 years versus older women (odds ratio (OR) 1.33; 95% CI 1.25-1.42), for the first versus subsequent screening rounds (OR 1.91; 95% CI 1.79-2.04) and with a centre-specific recall rate below the average of 6.2% (OR 1.41; 95% CI 1.32-1.50). RES predicted a 3.51-fold (95% CI 0.94-9.29) greater proportional incidence of first-year interval cancers, a 1.90-fold (95% CI 1.62-2.22) greater recall rate at the next screen, a 1.72-fold (95% CI 1.01-2.74) greater detection rate of cancer at the next screen and a non-significantly decreased risk of late disease stage (OR 0.59; 95% CI 0.23-1.53). CONCLUSION: The prevalence of RES was in line with the maximum standard level established by the Italian national guidelines. RES identified a subset of women with greater incidence of interval cancers and greater prevalence of cancers detected at the next screen.

Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study.

BACKGROUND: The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening. METHODS: A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age. RESULTS: A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age > or =45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/microl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied. CONCLUSIONS: In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.

Changes in the incidence of cervical tumours by disease stage in a cytology-based screening programme.

OBJECTIVES: To report changes in incidence of cervical tumours by disease stage, following the introduction of an organized cytology-based screening programme. METHODS: An intention-to-screen study of a cytology-based screening programme targeting 1,219,000 women aged 25-64 in northern Italy was carried out. Based on the previously reported trend in total incidence of cervical cancer, the study period 1995-2014 was divided into 1995-1996 (pre-screening, or reference, years), 1997-1998 (screening implementation phase), 1999-2006 (transition phase, when incidence decreased), and 2007-2014 (steady-state phase, when incidence stabilized again). Tumour stage was categorized as preinvasive (cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ), early (pT1a), advanced (pT1b or greater, ypT), and unknown (pT1 not otherwise specified, pTx, missing information). Average annual incidence rates observed in each phase were compared with the expected (reference) rates, using the incidence rate ratio, calculated with a Poisson regression model. RESULTS: In the steady-state phase, incidence rate ratios were: CIN3, 1.55 (95% confidence interval, 1.41-1.70); early-stage squamous carcinoma, 0.49 (0.36-0.67); advanced-stage squamous carcinoma, 0.44 (0.33-0.57); unknown-stage squamous carcinoma, 0.69 (0.48-0.99); adenocarcinoma in situ, 1.44 (0.72-2.88); early-stage adenocarcinoma, 2.65 (0.82-8.53); advanced-stage adenocarcinoma, 1.03 (0.56-1.91); and unknown-stage adenocarcinoma, 0.46 (0.23-0.92). CONCLUSIONS: After stabilization, changes in incidence by tumour stage included a 55% increase for CIN3 and a 50-55% decrease both for early- and advanced-stage squamous carcinoma, but no significant changes for glandular tumours. These data will serve to quantify the incremental impact of the implementation of human papillomavirus-based screening, introduced in 2015.

Evaluation of service mammography screening impact in Italy. The contribution of hazard analysis.

12,987 invasive breast cancer cases were diagnosed in women aged 50-69 upto the year 2001 in nine Italian areas where a screening programme was active. Cases were followed up in 2005 for a total of 1921 breast cancer failures. The 10-year survival rates were 85.3% for the invited group against 75.6% for the non-invited. A time dependent analysis was performed using 5-year intervals. Crude hazard ratios for the invited group in comparison to the not invited group were 0.52 and 0.64 respectively in the (0-5) year and [5-10] year time windows. Hazard ratio adjusted for tumour characteristics was 0.96 in the [5-10] year time window, suggesting minimal or any length bias. Consistent with the results of randomised trials, these analyses of service screening data document a mortality reduction of 36% at 5-10 years after diagnosis.

Screening for colorectal cancer in Italy: 2006 survey.

We present the main results of the third survey of the Italian screening programmes for colorectal cancer carried out by the ONS (Osservatorio Nazionale Screening, National Centre for Screening Monitoring) on behalf of the Ministry of Health. During 2006, many new programmes were activated and by the end of the year, 44% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Five regions had their entire population covered. In the South of Italy and Islands only one new programme was activated in 2006, with a 10% theoretical extension. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted the flexible sigmoidoscopy (PS) once in a lifetime, or a combination of both. Overall, about 2,107,000 subjects were invited to undergo FOBT, 70.3% of those to be invited within the year. The adjusted attendance rate was 44.6% and approximately 907,000 subjects were screened. Major differences in the attendance rate were observed among regions, with 10% of programmes reporting values lower than 26%. Positivity rate of FOBT programmes was 5.3% at first and 3.9% at repeat screening: it increased with age and was higher among males than females in all age groups. The average attendance rate to total colonoscopy (TC) was 81% (10th-9Oth percentiles: 64%, 93%). Completion rate of TC was 89%, with higher rates among males. At first screening, the detection rate (DR) per 1,000 screened subjects was 3.1 and 14.6 for invasive cancer and advanced adenomas (AA--adenomas with a diameter > or =1 cm, with villous/tubulo-villous type or with high-grade dysplasia), respectively; the corresponding figures at repeat screening were 1.3 per thousand for cancer and 7.7 per thousand for AA. The DR of cancer and adenomas increased with age and was higher among males; 25% of screen-detected cancers were in TNM stage III+. The positive predictive value (PPV) was 6.8% for cancer and 32.1% for AA at first screening, and 4.0% for cancer and 23.4% for AA at repeat screening. Given the high PPVof a positive FOBT, obtaining a high attendance at TC is therefore crucial. Seven programmes employed PS as the screening test: 51.4% of the target population (about 50,000 subjects) were invited and 7,589 subjects were screened, with an attendance rate of 29.2%. Overall, 88% of FS were classified as complete. TC referral rates ranged between 6.1 and 17.8%, due to different referral criteria. Among subjects referred to colonoscopy, the prevalence of proximal AA and cancer ranged from 6 to 18.2%. The overall DR (subjects with at least one advanced lesion) ranged from 4.9 to 7.5%. In conclusion, during 2006, organised colorectal cancer screening programmes in Italy grew considerably, covering almost half of the eligible population at a national level. Many programmes were activated in the second part of the year, thus their results should be evaluated with caution. However, reported experiences showed good results in terms of attendance and DR, although some critical aspects need to be carefully addressed when planning and implementing screening activity.

[Interval cancers as indicators of performance in screening programmes]. / I carcinomi di intervallo quali indicatori di performance di un programma di screening.

GISMa analyses the interval cancer (IS) topic providing guidelines and reference standards in addition to CE recommendations. IC identification is based on Cancer Registries (CR), if existing, or on hospital discharge records, in alternative. The optimal measure of IC frequency (inversely correlated with sensitivity) is the IC proportional incidence (observed IC/carcinomas expected in absence of screening). Other formulas (IC/IC + screen detected cancers; IC rate per 1000 negative screens) look less reliable. IC stage at diagnosis (if available through CR) must be compared with screen detected cancer and cancer detected in non-attenders. Review of mammograms preceding the IC (coded as screening error, minimal signs, or occult) should be done mainly with a blind procedure (IC mixed with negative controls), as this procedure is more representative of the original scenario and more respectful of radiologist's rights.

Follow-up of screening patients conservatively treated for cervical intraepithelial neoplasia grade 2-3.

OBJECTIVES: To evaluate the frequency and correlates of non-adherence to follow-up among patients conservatively treated for CIN2-3. STUDY DESIGN: Study population comprised 1560 patients aged 25-64 years from a screening programme in northern Italy. The regional standard protocol was used as a reference. Multinomial logistic regression analysis was used to estimate the odds ratio probability of a patient being lost to follow-up (no check-ups within 27 months of treatment) or incompletely followed-up (1-3 negative check-ups) versus having 4 negative check-ups. RESULTS: Three hundred twenty-six patients (21%) were lost to follow-up, 678 (43%) were incompletely followed-up, 352 (23%) presented for 4 negative check-ups and 204 (13%) were diagnosed with persistent disease. The probability of no or incomplete follow-up was greater for patients who lived in the urban district, who were treated in private settings (versus screening centres), who exhibited a visibile squamocolumnar junction on pre-treatment colposcopy, who were treated with cold knife excision and local destructive therapy (versus loop diathermy excision), and whose surgical specimens had positive excision margins. CONCLUSIONS: Adherence to the reference protocol was poor. Factors involved in follow-up failures require greater clinical attention.

[Ouality indicators for the evaluation of colorectal cancer screening programmes]. / Indicatori di qualità per la valutazione dei programmi di screening dei tumori colorettali.

Colorectal cancer screening programmes, which are supported by national and international recommendations, are gradually developing andspreading throughout Italy. The programmes strive to guarantee maximum equality, improve quality of life, and inform the target population about benefits and possible risks. These goals can only be achieved with adequate planning and training for the staff involved. Moreover, it is essential to regularly verify the quality of each step of the process, with a system that can constantly monitor the parameters used for the evaluation of quality and efficacy. The present document, created by the Italian Group for Colorectal Screening (GISCoR), proposes a unified method for collecting and reporting screening data using commonly agreed terminology, definitions and classifications, thus making it possible to compare data with standards and data from other programmes, and to plan suitable interventions. The indicators considered refer to the entire screening process, including organisational, logistic and performance indicators. The indicators are provided in the form of concise and easy-to-use data sheets. Every data sheet contains briefsections: definition of the indicator, goal, the data necessary to build it, the formula required to build it, possible problems of interpretation, acceptable and desirable standards.

[Process indicators and standards for the evaluation of breast cancer screening programmes]. / Indicatori e standard per la valutazione di processo dei programmi di screening del cancro della mammella.

In order to obtain the maximum benefit from breast cancer screening it is essential for every programme to reach high levels of sensitivity and specificity. This can only be achieved if skill and a comprehensive quality assurance system is applied to the entire process, involving each individual part of the programme. Monitoring of outcomes and continuous evaluation of the entire screening process are key operational objectives for a successful population screening programme. The aim of this document, born in the framework of the Italian Group for Mammography Screening (GISMa), is to propose a unique methodology for collecting and reporting screening data using commonly agreed terminology, definitions and classifications. The indicators considered are those referred to the entire screening process and its sequelae, such as organizational, logistic and performance indicators. The indicators are provided under form of a synthetic and easy to use card. Every card is structured in short sections: definition, aim of the indicator, the data necessary to build it, the summarizing formula, possible problems of interpretation, the acceptable and desirable standards (derived both from the experience of national and European breast cancer screening programmes).

Screening history of cervical cancers in Emilia-Romagna, Italy: defining priorities to improve cervical cancer screening.

Most invasive cervical cancers in industrialized countries are due to the lack of Pap test coverage, very few are due to screening failures. This study aimed at quantifying the proportion of invasive cancers occurring in nonscreened or underscreened women and that in women with a previous negative screening, that is, screening failure, during the first two screening rounds (1996-2002) and in the following rounds (2003-2008) in the Emilia-Romagna region. All cases of invasive cancers registered in the regional cancer registry between 1996 and 2008 were classified according to screening history through a record linkage with the screening programme registry. The incidence significantly decreased from 11.6/100 000 to 8.7/100 000; this decrease is due to a reduction in squamous cell cancers (annual percentage change -6.2; confidence interval: -7.8, -4.6) and advanced cancers (annual percentage change -6.6; confidence interval: -8.8, -4.3), whereas adenocarcinomas and microinvasive cancers were essentially stable. The proportion of cancers among women not yet invited and among nonresponders decreased over the two periods, from 45.5 to 33.3%. In contrast, the proportion of women with a previous negative Pap test less than 5 years and 5 years or more before cancer incidence increased from 5.7 to 13.3% and from 0.3 to 5.5%, respectively. Although nonattendance of the screening programme remains the main barrier to cervical cancer control, the introduction of a more sensitive test, such as the human papillomavirus DNA test, could significantly reduce the burden of disease.

Applicability of the Bethesda System 2001 to a public health setting.

BACKGROUND: The degree of applicability of the Bethesda System 2001 (TBS 2001) for cervicovaginal cytology to a public health setting is unknown, and extrapolations from available data are unwarranted. METHODS: A "before/after" study design was used to evaluate the impact of TBS 2001 on an organized, population-based screening program in northern Italy. Between 2003-2004, 6 cytology laboratories converted from TBS 1991 to TBS 2001. A set of screening indicators based on TBS 2001 (85,012 patients) were compared with those based on TBS 1991 (199,833 patients) by means of their laboratory- and patient age-standardized ratio with a 95% confidence interval (CI). RESULTS: The prevalence of cervical intraepithelial neoplasm (CIN)2-3/carcinoma was stable between the 2 populations. TBS 2001 had no effect on the unsatisfactory rate (1.99% vs. 2.03% for TBS 1991) nor on follow-up compliance rate (93.2% vs. 92.3%). The reporting rate of atypical squamous cells (ASC) decreased from 17.1 to 14.7 per 1000 (ratio, 0.86; 95% CI, 0.81-0.91), the total positivity rate from 31.1 to 29.0 per 1000 (ratio, 0.93; 95% CI, 0.90-0.97), and the ASC:SIL (squamous intraepithelial lesion) ratio from 1.38 to 1.16. Compared with the ASCUS (ASC of undetermined significance) reports of TBS 1991, the predictive value for CIN2-3/carcinoma decreased from 5.2 to 3.5% (ratio, 0.68; 95% CI, 0.48-0.93) among ASCUS reports, but increased from 5.1 to 17.2% (ratio, 3.41; 95% CI, 1.64-6.28) among ASC-cannot exclude high grade lesion (ASC-H) reports. ASC-H had a 5.01-fold (95% CI, 2.23-10.2) greater predictive value than ASCUS. CONCLUSIONS: TBS 2001 is applicable to cervical screening in a public health setting.