rubrica

Screening

  • Paolo Giorgi Rossi1

  1. Servizio interaziendale di epidemiologia, AUSL Reggio Emilia

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Ricerca bibliografica periodo dal 16 novembre 2013 al 31 gennaio 2014

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Stringa: ("mass screening"[MeSH Terms] OR cancer[Title/Abstract] AND screening[Title/Abstract] AND ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2013/11/16"[PDAT] : "2014/01/31"[PDAT])

Breve commento a cura di P. Giorgi Rossi
In questi 60 giorni abbiamo visto l’uscita delle due pubblicazioni su Lancet Oncology dei risultati di EUROCARE 5 (De Angelis per gli adulti e Gatta per i tumori pediatrici, non inclusa in questa selezione sugli screening per ovvi motivi), come al solito i risultati di questa monumentale collaborazione europea ci offrono molti spunti per riflettere sul ruolo dei servizi sanitari nel cambiare la sopravvivenza, ma anche su come, per alcune sedi, l’aumento di sopravvivenza sia tristemente dovuto più all’aumento dell’incidenza che alla riduzione della mortalità. Anche questo bimestre le pubblicazioni sullo screening mammografico sono frutto di collaborazioni, idee e passioni che furono di Stefano Ciatto: la valutazione dei cancri intervallo in tutti i programmi di screening (Carbonaro) e la sperimentazione della tomosintesi (Caumo) con lo studio STORM. Compaiono due nuove proposte di screening: endometrio (Fambrini) ed epatocarcinoma (Giannini e Cucchetti); questo conferma una tendenza della letteratura, italiana e non, a proporre sempre nuovi screening di difficile sostenibilità, anche per patologie a bassa letalità, come nel caso dell’endometrio, o su popolazioni ad “alto rischio” con definizioni piuttosto vaghe, come nel caso dell’epatocarcinoma. Ben quattro lavori riguardano l’HPV e lo screening della cervice uterina (Del Mistro, Tornesello, Pileggi e una revisione sistematica di Arbyn in collaborazione con il gruppo del CPO Piemonte). Due lavori sullo screening del carcinoma prostatico, uno metodologico (Zappa) sui dati del trial ERSPC e uno sperimentale sull’accuratezza del PCA3 (Capoluongo), uno studio sul Polmone (Sozzi) per la valutazione di biomarker nello studio MILD e uno sull’uso della CT per il colon retto (Fini) in soggetti con familiarità completano il quadro.

1. Del Mistro A, Frayle H, Ferro A, Callegaro S, Del Sole A, Stomeo A, Cirillo E, Fedato C, Pagni S, Barzon L, Zorzi M; on behalf of the Veneto HPV-screening Working Group. Cervical cancer screening by high risk HPV testing in routine practice: results at one year recall of high risk HPV-positive and cytology-negative women. J Med Screen. 2014 Jan 31. [Epub ahead of print]
Author information: Immunology and Molecular Oncology Unit, Veneto Oncology Institute IOV IRCCS, Padova, Italy.

Abstract
OBJECTIVE: Cervical cancer screening by human papillomavirus (HPV) testing requires the use of additional triage and follow-up analyses. We evaluated women's compliance with and the performance of this strategy in a routine setting. SETTING: Five cervical service screening programmes in North-East Italy. METHODS: Eligible women aged 25-64 invited for a new screening episode underwent HPV testing for high risk types (hrHPV by Hybrid Capture 2) and cytology triage. Women with positive HPV and cytology results were referred for colposcopy; women with positive HPV but negative cytology results were referred to 1-year repeat hrHPV testing. RESULTS: Of 46,694 women screened by HPV testing up to December 2011, 3,211 (6.9%) tested hrHPV positive; 45% of these had a positive triage cytology. Those with negative cytology were invited for 1-yr repeat testing. Compliance with invitation was 61.6% at baseline and 85.3% at 1-yr repeat. Rate of persistent hrHPV positivity was 58% (830/1,435). Colposcopy performed in women with a positive hrHPV test at 1-yr repeat accounted for 36% of all colposcopies performed within the screening programmes. Cumulatively, a histological high-grade lesion was detected in 276 women (5.9‰ detection rate), 234 at baseline (85%), and 42 (15%) at 1-yr repeat. CONCLUSIONS: Compliance with hrHPV-based screening programmes was high both at baseline and at 1-yr repeat. Compared with the randomized trials, a higher proportion of triage cytology was read as positive, and only a small number of high-grade lesions were detected among the group of hrHPV positive cytology negative women who repeated testing 1-yr after baseline.

2. Fini L, Laghi L, Hassan C, Pestalozza A, Pagano N, Balzarini L, Repici A, Pickhardt PJ, Malesci A. Noncathartic CT Colonography to Screen for Colorectal Neoplasia in Subjects with a Family History of Colorectal Cancer. Radiology. 2013 Nov 22:130373. [Epub ahead of print]
Author information: From the Humanitas Clinical and Research Center (L.F., L.L., A.P., L.B., A.M.) and Digestive Endoscopy Unit (N.P., A.R.), Istituto Clinico Humanitas, Milan, Italy; Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Via Morosini 30, Rome 00153, Italy (C.H.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P.); and Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy (A.M.).

Abstract
Purpose To prospectively assess the diagnostic performance of noncathartic computed tomographic (CT) colonography in the detection of clinically relevant colorectal lesions (≥6 mm polyps or masses) in a well-defined cohort of first-degree relatives of patients with colorectal cancer (CRC), using colonoscopy and histologic review as the standard of reference. Materials and Methods Institutional review board approval was obtained, and all subjects provided written informed consent. Consecutive patients admitted with CRC (index cases) were prospectively evaluated, and those who agreed to contact their first-degree relatives who were at least 40 years old were included. Available first-degree relatives were invited to undergo noncathartic CT colonography (200 mL of diatrizoate meglumine and diatrizoate sodium). Colonoscopy was performed the following day, and findings from CT colonography were disclosed for each segment. Sensitivity, specificity, and positive and negative predictive values of CT colonography were assessed for detecting subjects with any lesion at least 6 mm, any lesion at least 10 mm, and advanced neoplasia at least 6 mm. Colonoscopy with segmental unblinding and histologic diagnosis were used as the standard of reference. Matching between findings from CT colonography and colonoscopy was allowed when lesions were located in the same or adjacent colon segments and when the size difference was 50% or less. Results Three hundred four first-degree relatives (median age, 47 years; age range, 40-79 years; 46.7% women) identified from 221 index cases were included. Overall, CT colonography helped identify 17 of 22 subjects with polyps measuring at least 6 mm (sensitivity, 0.77; 95% confidence interval [CI]: 0.59, 0.95) and helped correctly classify as negative 278 of 282 subjects without lesions measuring at least 6 mm (specificity, 0.99; 95% CI: 0.97, 1.00). CT colonography helped detect eight of nine subjects with polyps measuring at least 10 mm as well as eight of nine subjects with advanced neoplasia measuring at least 6 mm (sensitivity, 0.89 for both). Per-subject positive and negative predictive values for lesions measuring at least 6 mm were 0.81 (17 of 21 subjects; 95% CI: 0.65, 0.97) and 0.98 (282 of 287 subjects; 95% CI: 0.96, 0.99), respectively. Conclusion Noncathartic CT colonography is an effective screening method in first-degree relatives of patients with CRC

3. Fambrini M, Sorbi F, Sisti G, Cioni R, Turrini I, Taddei G, Guaschino S. Endometrial carcinoma in high-risk populations: is it time to consider a screening policy? Cytopathology. 2014 Jan 27. doi: 10.1111/cyt.12131. [Epub ahead of print]
Author information: Department of Biomedical, Clinical and Experimental Sciences, University of Florence, Florence, Italy.

Abstract
Endometrial carcinoma (EC) is the leading female genital tract malignancy in industrialized countries. It will become an important public health problem in the coming years in the USA and Europe, where its incidence is increasing, and next-generation interventions should include periodical screening in high-risk women. In this review, we discuss the importance to gynaecologists of detecting women at high risk and offering an adequate screening programme. Screening for EC is particularly challenging and there is currently no proven programme for the surveillance of women estimated to be at an increased risk of developing this form of cancer. The data in the literature, including this and previous issues of Cytopathology, and personal experience suggest that endometrial liquid-based cytology (LBC) might play an essential role in a screening policy for EC. LBC may enable practitioners to reduce age-adjusted mortality for women at high risk for EC.

4. Arbyn M(1), Verdoodt F(2), Snijders PJ(3), Verhoef VM(3), Suonio E(4), Dillner L(5), Minozzi S(6), Bellisario C(6), Banzi R(7), Zhao FH(8), Hillemanns P(9), Anttila A(10). Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 2014 Feb;15(2):172-83. doi: 10.1016/S1470-2045(13)70570-9. Epub 2014 Jan 14.
Author information: (1)Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium. Electronic address: marc.arbyn@wiv-isp.be. (2)Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium. (3)Department of Pathology, VU University Medical Center, Amsterdam, Netherlands. (4)International Agency for Research on Cancer, Lyon, France. (5)Karolinska Institute, Stockholm, Sweden. (6)Unit of Cancer Epidemiology, Department of Oncology, Piedmont Centre for Cancer Prevention, S Giovanni University Hospital, Turin, Italy. (7)IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. (8)Department of Cancer Epidemiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China. (9)Department of Gynaecology and Obstetrics, Hannover Medical School, Hannover, Germany. (10)Finnish Cancer Registry, Helsinki, Finland.

Abstract
BACKGROUND: Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. METHODS: We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. FINDINGS: We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84% (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0•88 [95% CI 0•85-0•91] for CIN2 or worse and 0•89 [0•83-0•96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0•96 [0•95-0•97] for CIN2 or worse and 0•96 [0•93-0•99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. INTERPRETATION: In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. FUNDING: The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.

5. Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, Roz L, Conte D, Grassi M, Sverzellati N, Marchiano A, Negri E, La Vecchia C, Pastorino U. Clinical Utility of a Plasma-Based miRNA Signature Classifier Within Computed Tomography Lung Cancer Screening: A Correlative MILD Trial Study. J Clin Oncol. 2014 Jan 13. [Epub ahead of print]
Author information: Gabriella Sozzi, Mattia Boeri, Carla Verri, Paola Suatoni, Luca Roz, Davide Conte, Michela Grassi, Tumor Genomics Unit; Ugo Pastorino, Thoracic Surgery Unit; Alfonso Marchiano, Radiology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori; Marta Rossi, Francesca Bravi, Eva Negri, Carlo La Vecchia, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri"; Francesca Bravi and Carlo La Vecchia, University of Milan, Milan; and Nicola Sverzellati, University of Parma, Parma, Italy.

Abstract
PURPOSE: Recent screening trial results indicate that low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of a noninvasive plasma microRNA signature classifier (MSC) was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicenter Italian Lung Detection (MILD) trial. PATIENTS AND METHODS: Plasma samples from 939 participants, including 69 patients with lung cancer and 870 disease-free individuals (n = 652, LDCT arm; n = 287, observation arm) were analyzed by using a quantitative reverse transcriptase polymerase chain reaction-based assay for MSC. Diagnostic performance of MSC was evaluated in a blinded validation study that used prespecified risk groups. RESULTS: The diagnostic performance of MSC for lung cancer detection was 87% for sensitivity and 81% for specificity across both arms, and 88% and 80%, respectively, in the LDCT arm. For all patients, MSC had a negative predictive value of 99% and 99.86% for detection and death as a result of disease, respectively. LDCT had sensitivity of 79% and specificity of 81% with a false-positive rate of 19.4%. Diagnostic performance of MSC was confirmed by time dependency analysis. Combination of both MSC and LDCT resulted in a five-fold reduction of LDCT false-positive rate to 3.7%. MSC risk groups were significantly associated with survival (χ1(2) = 49.53; P < .001). CONCLUSION: This large validation study indicates that MSC has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT, thus improving the efficacy of lung cancer screening.

6. Zappa M(1), Puliti D(2), Hugosson J(3), Schröder FH(4), van Leeuwen PJ(4), Kranse R(5), Auvinen A(6), Carlsson S(7), Kwiatkowski M(8), Nelen V(9), Borda AP(10), Roobol MJ(4), Villers A(11) A Different Method of Evaluation of the ERSPC Trial Confirms That Prostate-specific Antigen Testing Has a Significant Impact on Prostate Cancer Mortality. Eur Urol. 2014 Jan 7. pii: S0302-2838(13)01480-2. doi: 10.1016/j.eururo.2013.12.055. [Epub ahead of print]
Author information: (1)Clinical and Descriptive Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. Electronic address: m.zappa@ispo.toscana.it. (2)Clinical and Descriptive Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. (3)Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden. (4)Department of Urology, Erasmus MC, Rotterdam, The Netherlands. (5)Department of Urology, Erasmus MC, Rotterdam, The Netherlands; Comprehensive Cancer Centre The Netherlands, Utrecht, The Netherlands. (6)School of Health Sciences, University of Tampere, Tampere, Finland. (7)Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA. (8)Department of Urology, Kantonsspital Aarau, Aarau, Switzerland; Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany. (9)Provinciaal Instituut voor Hygiëne, Antwerp, Belgium. (10)Department of Urology, Hospital Universitario de Fuenlabrada, Madrid, Spain. (11)Department of Urology, CHU Lille, University Lille Nord de France, Lille, France.

Abstract
The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality.

7. Tornesello ML(1), Buonaguro L(1), Giorgi-Rossi P(2), Buonaguro FM(1). Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013;2013:519619. doi: 10.1155/2013/519619. Epub 2013 Dec 9.
Author information: (1)Molecular Biology and Viral Oncology, National Cancer Institute "Fondazione Pascale", Cappella Cangiani, 80131 Naples, Italy. (2)Servizio Interaziendale di Epidemiologia, AUSL Reggio Emilia, 42121 Reggio Emilia, Italy.

Abstract
Cervical cancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV) genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1) increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2) integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3) molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervical cancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a) and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervical cancer.

8. Giannini EG, Cucchetti A, Erroi V, Garuti F, Odaldi F, Trevisani F. Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it? World J Gastroenterol. 2013 Dec 21;19(47):8808-21. doi: 10.3748/wjg.v19.i47.8808.
Author information: Edoardo G Giannini, Dipartimento di Medicina Interna, Unità di Gastroenterologia, Università di Genova, IRCCS-Azienda Ospedaliera San Martino-IST, 16155 Genova, Italy.

Abstract
Surveillance for hepatocellular carcinoma (HCC) is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy. Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments. Repetition of liver ultrasonography (US) every 6 mo is the recommended surveillance program to detect early HCCs, and a positive US has to entrain a well-defined recall policy based on contrast-enhanced, dynamic radiological imaging or biopsy for the diagnosis of HCC. Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance, the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure. Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC. The promotion of specific educational programs for practitioners, clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.

9. Carbonaro LA(1), Azzarone A(2), Paskeh BB(3), Brambilla G(4), Brunelli S(5), Calori A(2), Caumo F(5), Malerba P(4), Menicagli L(3), Sconfienza LM(6), Vadalà G(2), Brambilla G(7), Fantini L(7), Ciatto S(8), Sardanelli F(6). Interval breast cancers: Absolute and proportional incidence and blinded review in a community mammographic screening program. Eur J Radiol. 2014 Feb;83(2):e84-91. doi: 10.1016/j.ejrad.2013.11.025. Epub 2013 Dec 6.
Author information: (1)Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097, Italy(2). Electronic address: luca.carbonaro@gmail.com. (2)Servizio di Radiologia, Azienda Ospedaliera Circolo di Melegnano, Via Pandina 1, Vizzolo Predabissi (Mi) 20070, Italy(3). (3)Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097, Italy(2). (4)Dipartimento di Radiologia, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, Rozzano (Mi) 20089, Italy(4). (5)Centro di Prevenzione Senologica, ULSS 20, Piazza Lambranzi, Verona 37034, Italy(5). (6)Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097, Italy(2); Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy. (7)Servizio di Medicina Preventiva delle Comunità, ASL Milano 2, Via Friuli 2, Lacchiarella (Mi) 20084, Italy(6). (8)Screening Program, ULSS 16, Padova, Italy.

Abstract
PURPOSE: To evaluate the performance of the first years since the beginning of a mammographic population-based screening program. MATERIALS AND METHODS: Women aged 49-69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared. RESULTS: A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p=0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25%, 7/28) was higher than that for true ICs (10%, 7/71), although all these differences were not significant (p≥0.480). CONCLUSION: These results showed the possibility to comply with European Community standards in the first years of a screening program implementation.

10. Caumo F(1), Bernardi D(2), Ciatto S(3), Macaskill P(4), Pellegrini M(2), Brunelli S(1), Tuttobene P(2), Bricolo P(1), Fantò C(2), Valentini M(2), Montemezzi S(1), Houssami N(5). Incremental effect from integrating 3D-mammography (tomosynthesis) with 2D-mammography: Increased breast cancer detection evident for screening centres in a population-based trial. Breast. 2014 Feb;23(1):76-80. doi: 10.1016/j.breast.2013.11.006. Epub 2013 Dec 6.
Author information: (1)Centro di Prevenzione Senologica, Marzana, Verona, Italy. (2)U.O. Senologia Clinica e Screening Mammografico, Department of Diagnostics, Azienda Provinciale Servizi Sanitari (APSS), Trento, Italy. (3)Centro di Prevenzione Senologica, Marzana, Verona, Italy; U.O. Senologia Clinica e Screening Mammografico, Department of Diagnostics, Azienda Provinciale Servizi Sanitari (APSS), Trento, Italy. (4)Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia. (5)Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia. Electronic address: nehmath@med.usyd.edu.au.

Abstract
BACKGROUND & OBJECTIVES: Three-dimensional (3D)-mammography (tomosynthesis) may improve breast cancer detection. We examined centre-specific effect of integrated 2D/3D mammography based on the STORM (screening with tomosynthesis or standard mammography) trial. METHODS: Asymptomatic women who attended population-based screening through Trento and Verona screening centres were recruited into STORM, a prospective comparison of screen-reading in two sequential phases: 2D-mammography only and integrated 2D/3D mammography. Outcomes were the number and rates of detected cancers and of false positive recalls (FPR), and incremental cancer detection rate (CDR). Paired binary data were compared using Mc Nemar's test. RESULTS: Of 33 cancers detected in Trento, 21 were detected at both 2D and 2D/3D screening, 12 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P < 0.001). Of the 26 cancers detected in Verona, 18 were detected at both 2D and 2D/3D screening, 8 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P = 0.008). There were no differences between centres in baseline CDR, and incremental CDR attributable to 3D-mammography was similar for Trento (2.8/1000 screens) and for Verona (2.6/1000 screens). Trento had 239 FPR (5.7% of screens): 103 FPR at both screen-readings, 93 FPR only at 2D-mammography compared with 43 FPR only at 2D/3D-mammography (p < 0.001). Verona had 156 FPR (5.2% of screens): 78 FPR at both screen-readings, 48 FPR only at 2D-mammography compared with 30 FPR only at 2D/3D-mammography (p = 0.054). Estimated reduction in FPR proportion had recall been conditional to 2D/3D-mammography-positivity differed between centres (21.0% versus 11.5%; P = 0.02). CONCLUSION: Integrated 2D/3D-mammography significantly increased cancer detection for both screening services; potential reduction in FPR is likely to differ between centres with those experiencing relatively higher FPR most likely to benefit from 2D/3D-mammography screening.

11. De Angelis R(1), Sant M(2), Coleman MP(3), Francisci S(4), Baili P(2), Pierannunzio D(4), Trama A(5), Visser O(6), Brenner H(7), Ardanaz E(8), Bielska-Lasota M(9), Engholm G(10), Nennecke A(11), Siesling S(6), Berrino F(5), Capocaccia R(4); EUROCARE-5 Working Group. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol. 2014 Jan;15(1):23-34. doi: 10.1016/S1470-2045(13)70546-1. Epub 2013 Dec 5.
Author information: (1)Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Rome, Italy. Electronic address: roberta.deangelis@iss.it. (2)Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy. (3)Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. (4)Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Rome, Italy. (5)Evaluative Epidemiology Unit, Department of Preventive and Predictive Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy. (6)Comprehensive Cancer Center the Netherlands, Utrecht, Netherlands. (7)Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. (8)Registro de Cáncer de Navarra, Instituto de Salud Pública de Navarra, Pamplona, Spain. (9)National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland. (10)Danish Cancer Society, Copenhagen, Denmark. (11)Hamburg Cancer Registry, Hamburg, Germany.

Abstract
BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. METHODS: In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). FINDINGS: 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73•4% [95% CI 72•9-73•9] vs 81•7% [81•3-82•1]), non-Hodgkin lymphoma (53•8% [53•3-54•4] vs 60•4% [60•0-60•9]), and rectal cancer (52•1% [51•6-52•6] vs 57•6% [57•1-58•1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. INTERPRETATION: The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.

12. Pileggi C, Flotta D, Bianco A, Nobile CG, Pavia M. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials. Int J Cancer. 2013 Dec 3. doi: 10.1002/ijc.28640. [Epub ahead of print]
Author information: Department of Health Sciences, Chair of Hygiene, Medical School, University of Catanzaro "Magna Graecia", Catanzaro, Italy.

Abstract
Human-papillomavirus (HPV) DNA testing has been proposed as an alternative to primary cervical cancer screening using cytological testing. Review of the evidence shows that available data are conflicting for some aspects. The overall goal of the study is to update the performance of HPV DNA as stand-alone testing in primary cervical cancer screening, focusing particularly on the aspects related to the specificity profile of the HPV DNA testing in respect to cytology. We performed a meta-analysis of randomized controlled clinical trials. Eight articles were included in the meta-analysis. Three outcomes have been investigated: relative detection, relative specificity, and relative positive predictive value (PPV) of HPV DNA testing versus cytology. Overall evaluation of relative detection showed a significantly higher detection of CIN2+ and CIN3+ for HPV DNA testing versus cytology. Meta-analyses that considered all age groups showed a relative specificity that favored the cytology in detecting both CIN2+ and CIN3+ lesions whereas, in the ≥30 years' group, specificity of HPV DNA and cytology tests was similar in detecting both CIN2+ and CIN3+ lesions. Results of the pooled analysis on relative PPV showed a not significantly lower PPV of HPV DNA test over cytology. A main key finding of the study is that in women aged ≥30, has been found an almost overlapping specificity between the two screening tests in detecting CIN2 and above-grade lesions. Therefore, primary screening of cervical cancer by HPV DNA testing appears to offer the right balance between maximum detection of CIN2+ and adequate specificity, if performed in the age group ≥30 years.

13. Capoluongo E(1), Zambon CF(2), Basso D(2), Boccia S(3), Rocchetti S(4), Leoncini E(3), Palumbo S(4), Padoan A(2), Albino G(4), Todaro A(5), Prayer-Galetti T(5), Zattoni F(5), Zuppi C(4), Plebani M(6). PCA3 score of 20 could improve prostate cancer detection: Results obtained on 734 Italian individuals. Clin Chim Acta. 2014 Feb 15;429:46-50. doi: 10.1016/j.cca.2013.10.022. Epub 2013 Nov 20.
Author information: (1)Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, Italy. Electronic address: ecapoluongo@rm.unicatt.it. (2)Department Laboratory Medicine, DIMED, University of Padova, Italy. (3)Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore of Rome, Italy. (4)Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, Italy. (5)Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, DiSCOG, Italy. (6)Department Laboratory Medicine, DIMED, University of Padova, Italy. Electronic address: mario.plebani@unipd.it.

Abstract
BACKGROUND: The role of PCa3 score in the diagnostics of prostate cancer (PCa) is still under debate, mainly due to the lack of a univocal cut-off useful alone or within nomograms proposed by Urologists. Aim of present study is to compare different PCA3 score cut-off values (20, 25, 35 and 50) observed in 734 patients with suspected PCa who were monitored for about three years with single or multiple biopsies. METHODS: 734 patients who underwent first prostate biopsy for suspected PCa were enrolled. One month later the first biopsy result was obtained, both negative and positive PCa patients were investigated by means of PCA3 score, in order to establish risk of PCa presence on repeated biopsies. RESULTS: PCA3 score was significantly higher (p<0.001) in PCa patients to the PCa negative ones, while tPSA did not significantly vary. The best negative predictive value (NPV 97.5%) and sensitivity (95.4%) result were obtained when a PCA3 score of 20 was used. At cut-off value of 50, the 75% of patients resulted as false positive. CONCLUSIONS: PCA3 score of 20 could be safely introduced in the prostate cancer screening diagnostic flow chart, since it provides important information regarding the outcome of re-biopsy.

14. Cucchetti A, Cescon M, Erroi V, Pinna AD Cost-effectiveness of liver cancer screening. Best Pract Res Clin Gastroenterol. 2013 Dec;27(6):961-72. doi: 10.1016/j.bpg.2013.08.021. Epub 2013 Oct 4.
Author information: General Surgery and Transplant Unit, Department of Medical and Surgical Sciences - DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Via Massarenti n° 9, 40138 Bologna, Italy. Electronic address: aleqko@libero.it.

Abstract
Screening for primary liver cancer means surveillance for hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. Detection of HCC for curative treatment is increased by surveillance, but target population, optimal periodicity and cost-effectiveness aspects are still debated issues. The aim of surveillance is to obtain a reduction in HCC-related mortality and this is usually achieved through an early diagnosis that increases both applicability and cost-effectiveness of curative treatments. The aim of the present review is to analyse economic aspects of HCC surveillance. Articles that assessed cost-effectiveness of surveillance for HCC, published between 1996 and February 2013, were reviewed in order to verify the cost-effectiveness of surveillance, its optimal periodicity, the target population and the role of alternative surveillance strategies. International guidelines are currently based on the results of such cost-effectiveness analyses, highlighting the importance of the release of cost-effectiveness-guided guidelines for HCC management.

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