rubrica

Screening

  • Paolo Giorgi Rossi1

  1. AUSL Reggio Emilia
Paolo Giorgi Rossi -

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Ricerca bibliografica periodo dal 16 agosto 2012 al 31 ottobre 2012

Per leggere le caratteristiche di questa ROUTINE di ricerca clicca qui

Stringa: ("mass screening"[MeSH Terms] OR cancer[Title/Abstract] AND screening[Title/Abstract] AND ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2012/08/16"[PDAT] : "2012/10/31"[PDAT])

Breve commento a cura di P. Giorgi Rossi
Anche in questa edizione della rubrica troviamo una proposta per un novo screening: l’adenocarcinoma del pancreas (Fiorino). È una proposta che si basa sul possibile ruolo di virus come l’HCV e l’HBV nell’eziopatogenesi e dunque sulla possibilità di individuare un gruppo di popolazione ad alto rischio da tenere sotto sorveglianza. Due lavori riguardano i metodi per aumentare la partecipazione agli screening (Ferroni, Hassan) e sono rielaborazioni ed aggiornamenti del rapporto HTA sullo stesso argomento pubblicato in gennaio proprio su E&P. Due lavori propongono la validazione di nuovi test (Rubeca), o combinazioni di test (Parente), fecali per lo screening del colon retto. Un lavoro su Endoscopy (Minozzi) presenta la metodologia utilizzata nella sintesi delle evidenze e produzione delle raccomandazioni per le linee guida europee sullo screening del colone retto uscite a inizio 2011. Due lavori (Giorgi Rossi et al, Giorgi Rossi & Ronco), con approcci differenti, cercano di delineare quale potrà essere il protocollo di screening del cervicocarcinoma nelle donne vaccinate. Sempre sulla cervice uterina vengono presentati su J Medical Virology (Tanzi) i risultati di accuratezza analitica di un test per la ricerca dell’HPV su campioni di urine; siamo ancora lontani da una validazione clinica, utile per licenziare il test per lo screening, ma la possibilità di eliminare le operazioni di prelievo da parte di personale sanitario è molto interessante nello screening della cervice. Due lavori sulla mammella vengono dall’ISPO di Firenze: uno sulla riduzione di mortalità causa specifica osservata negli studi europei (Puliti) e uno sulla caratterizzazione dei biomarker espressi dai carcinomi d’intervallo confrontati con gli screen-detected (Caldarella). Infine il lavoro, a mio parere, più innovativo: i risultati del trial SPRINT, un intervento di counselling per la cessazione del fumo e la promozione dell’attività fisica condotto da ostetriche in occasione del prelievo per il Pap test di screening. L’intervento si è dimostrato efficace nella cessazione del fumo e nel ridurre il numero di sigarette, ma non ha mostrato alcun effetto sull’attività fisica.

1. Rossi PG, Sideri M, Carozzi FM, Vocaturo A, Buonaguro FM, Tornesello ML, Burroni E, Mariani L, Boveri S, Zaffina LM, Chini F; the HPV Prevalence Italian Working Group. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies. Infect Agent Cancer. 2012 Oct 12;7(1):26. [Epub ahead of print]

Abstract
ABSTRACT: OBJECTIVE: The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. METHODS: A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. RESULTS: Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend < 0.005). CONCLUSIONS: The impact of HPV 16/18 vaccine on cervical cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection.

2. Tanzi E, Bianchi S, Fasolo MM, Frati ER, Mazza F, Martinelli M, Colzani D, Beretta R, Zappa A, Orlando G High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping. J Med Virol. 2012 Oct 23. doi: 10.1002/jmv.23434. [Epub ahead of print]
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; CIRI-IV, Department of Health Sciences, University of Genoa, Genoa, Italy. elisabetta.tanzi@unimi.it.

Abstract
Human papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR-based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV-DNA detection and genotyping using a PCR-based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemar's test for differences. Concordance between tests was assessed using the Cohen's unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1-73.1%) of both cytobrush and urine samples. High concordance rates of HPV-DNA detection (k = 0.96; 95% CI: 0.90-1.0) and of high risk-clade and low-risk genotyping in paired samples (k = 0.80; 95% CI: 0.67-0.92 and k = 0.74; 95% CI: 0.60-0.88, respectively) were observed. HPV-DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1-99.9%) and a specificity of 97.4% (95% CI: 87.7-99.9%), with a very high NPV (97.4%; 95% CI: 87.7-99.9%). The PCR-based assay utilized in this study proved highly sensitive and specific for HPV-DNA detection and genotyping in urine samples. These data suggest that a urine-based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs.

3. Ferroni E, Camilloni L, Jimenez B, Furnari G, Borgia P, Guasticchi G, Rossi PG; the Methods to increase participation Working Group. How to increase uptake in oncologic screening: A systematic review of studies comparing population-based screening programs and spontaneous access. Prev Med. 2012 Oct 11. pii: S0091-7435(12)00481-1. doi: 10.1016/j.ypmed.2012.10.007.
Laziosanità, Public Health Agency, Lazio Region, Rome, Italy.

Abstract
BACKGROUND.: Cervical, breast and colorectal cancer (CRC) screenings are universally recommended interventions. High coverage of the target population represents the most important factor in determining their success. This systematic review aimed at assessing the effectiveness of population-based screening programs in increasing coverage compared to spontaneous access. METHODS.: Electronic databases and national and regional websites were searched. We included all studies on interventions aimed at increasing screening participation published between 1999 and 2009; for those published before, we consulted the Jepson et al. review (2000). We compared spontaneous access (including no intervention) vs population-based screening programs actively inviting the target population. Among the latter, we compared GP-based vs invitation letter-based interventions. RESULTS.: The invitation letter vs no intervention showed significantly more participation (RR=1.60 95%CI 1.33-1.92; RR=1.52 95%CI 1.28-1.82; RR=1.15 95%CI 1.12-1.19, for breast, cervical and CRC screenings, respectively). GP-based interventions, although more heterogeneous, showed a significant effect when compared with no intervention for breast (RR=1.74 95%CI 1.25-2.43), but not for cervical and CRC. No significant differences were found between invitation letter-based and GP-based organization (RR=0.99 95%CI 0.94-1.05; RR=1.08 95%CI 0.99-1.17, for breast and cervical cancer, respectively). CONCLUSION.: Population-based programs are more effective than spontaneous screening in obtaining higher testing uptake. Both invitation letter-based and GP-based programs are effective.

4. Hassan C, Giorgi Rossi P, Camilloni L, Rex DK, Jimenez-Cendales B, Ferroni E, Borgia P, Zullo A, Guasticchi G, Group H. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther. 2012 Nov;36(10):929-40. doi: 10.1111/apt.12071. Epub 2012 Oct 4.
Laziosanità Agenzia di Sanità Pubblica, Regione Lazio, Rome, Italy; Division of Gastroenterology, 'Nuovo regina Margherita' Hospital, Rome, Italy.

Abstract
BACKGROUND: A variety of tests have been proposed for colorectal cancer (CRC), giving rise to uncertainty regarding the optimal approach. The efficacy and effectiveness of different tests are related to both screenee participation and the detection rate. AIM: To perform a meta-analysis on adherence and detection rates of CRC screening tests. METHODS: Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1999-2012. A previous systematic review was used for the period before 1966-1999. RCTs and controlled studies including a direct comparison of the uptake rates among different options for CRC screening were included. Adherence and detection rates for advanced neoplasia and cancer were extracted. Risk for bias was ascertained according to CONSORT guidelines. Forrest plots were produced based on random-effect models. RESULTS: Fourteen studies provided data on 197 910 subjects. Endoscopic strategies were associated with a lower participation (RR: 0.67, 95% CI: 0.56, 0.80) rate, but a higher detection rate of advanced neoplasia (RR: 3.21, 95% CI: 2.38, 4.32) compared with faecal tests. FIT was superior to g-FOBT with regard to both adherence (RR: 1.16, 95% CI 1.03, 1.30) and detection of advanced neoplasia (RR: 2.28, 95% CI 1.68, 3.10) and cancer (RR: 1.96, 95% CI: 1.2, 3.2). CONCLUSION: The superior accuracy of endoscopy compared with faecal tests minimised any impact of the participation rate in determining the detection rate of advanced neoplasia in a screening setting.

5. Minozzi S, Armaroli P, Segnan N. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition - Principles of evidence assessment and methods for reaching recommendations. Endoscopy. 2012 Sep;44 Suppl 3:SE9-SE14. Epub 2012 Sep 25./div>
CPO Piemonte (Piedmont Centre for Cancer Prevention) and S. Giovanni Hospital, Turin, Italy.

Abstract
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The principles of evidence assessment and methods for reaching recommendations are presented here to promote international discussion and collaboration by making the principles and methods used in developing the guidelines known to a wider professional and scientific community. Following this methodology in the future updating of the guidelines has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multidisciplinary diagnosis and management of the disease.

6. Rossi PG, Ronco G. The Present and Future of Cervical Cancer Screening Programmes in Europe. Curr Pharm Des. 2012 Sep 24. [Epub ahead of print]
AUSL Reggio Emilia, Epidemiology Unit, Reggio Emilia, via Amendola 2, 42122, Reggio Emilia, Italy. Paolo.giorgirossi@ausl.re.it.

Abstract
The identification of HPV as the cause of cervical cancer has changed the information required for surveillance. HPV prevalence and screening uptake worldwide are now necessary to describe the epidemiology of this cancer. In low-income countries cervical cancer incidence varies from low to very high levels and is strongly influenced by virus prevalence. In high-income countries, instead, incidence is low and little influenced by the virus prevalence, thanks to screening. The European Guidelines currently recommend Pap test every 3-5 years starting at age 22-30 and stopping at age 60-65. HPV testing is now limited to triage of borderline lesions? and to post-CIN follow up. Pilot studies evaluating HPV testing as primary test are recommended. Future governmental agency Guidelines in Europe will probably include HPV testing as viable for primary screening, with cytology triage for HPV-positive women (those positive to cytology will be directly referred to colposcopy, those negative will repeat HPV at one year. Persistence of HPV positivity will refer to colposcopy directly, clearance to regular screening). The interval after an HPV-negative test should be at least 5 years and starting age should be age 30/35. Pap test is still recommended for women under 30.

7. Puliti D, Zappa M. Breast cancer screening: are we seeing the benefit? BMC Med. 2012 Sep 20;10:106.
Clinical and Descriptive Epidemiology Unit, ISPO - Cancer Prevention and Research Institute, Via delle Oblate 2, 50141 Florence, Italy. m.zappa@ispo.toscana.it.

Abstract
ABSTRACT: A decline in breast cancer mortality has been observed in western European Countries since the middle of the 1990s.Different methodological approaches, including case-control studies, incidence-based mortality studies, and trend studies, have been used to assess the effectiveness of mammography screening programmes in reducing breast cancer mortality. However, not all methods succeed in distinguishing the relative contributions of service screening and taking correctly into consideration the potential source of bias that might affect the estimate.Recently, a review of six case-control studies confirmed a breast cancer mortality reduction ranging from 38% to 70% among screened women. This figure is in accordance with the estimate obtained from incidence-based mortality studies if screening compliance is taken into account. We will describe the methodological constraints of mortality trend studies in predicting the impact of screening on mortality and the necessary caution that must be applied when interpreting the results of such studies.In conclusion, when appropriate methodological approaches are used, it is evident that mammographic screening programmes have contributed substantially to the observed decline in breast cancer mortality.

8. Caldarella A, Puliti D, Crocetti E, Bianchi S, Vezzosi V, Apicella P, Biancalani M, Giannini A, Urso C, Zolfanelli F, Paci E. Biological characteristics of interval cancers: a role for biomarkers in the breast cancer screening.
Clinical and Descriptive Epidemiology Unit, Institute for Study and Cancer Prevention (ISPO), Via delle Oblate 2, 50141, Florence, Italy, a.caldarella@ispo.toscana.it.

Abstract
INTRODUCTION: In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes. MATERIALS AND METHODS: We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki67 <14 %, luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive if ER/PR- and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables. RESULTS: Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709). CONCLUSION: Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies.

9. Fiorino S, Lorenzini S, Masetti M, Deleonardi G, Grondona AG, Silvestri T, Chili E, Del Prete P, Bacchi-Reggiani L, Cuppini A, Jovine E. Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma. Med Hypotheses. 2012 Nov;79(5):678-97. doi: 10.1016/j.mehy.2012.08.008. Epub 2012 Sep 5.
Unità Operativa di Medicina Interna, Ospedale di Budrio, Budrio, Bologna, Italy. Electronic address: sirio.fiorino@ausl.bologna.it.

Abstract
Pancreatic adenocarcinoma (PAC) is a very aggressive and lethal cancer, with a very poor prognosis, because of absence of early symptoms, advanced stage at presentation, early metastatic dissemination and lack of both specific tests to detect its growth in the initial phases and effective systemic therapies. To date, the causes of PAC still remain largely unknown, but multiple lines of evidence from epidemiological and laboratory researches suggest that about 15-20% of all cancers are linked in some way to chronic infection, in particular it has been shown that several viruses have a role in human carcinogenesis. The purpose of this report is to discuss the hypothesis that two well-known oncogenic viruses, Human B hepatitis (HBV) and Human C hepatitis (HCV) are a possible risk factor for this cancer. Therefore, with the aim to examine the potential link between these viruses and PAC, we performed a selection of observational studies evaluating this association and we hypothesized that some pathogenetic mechanisms involved in liver carcinogenesis might be in common with pancreatic cancer development in patients with serum markers of present or past HBV and HCV infections. To date the available observational studies performed are few, heterogeneous in design as well as in end-points and with not univocal results, nevertheless they might represent the starting-point for future larger and better designed clinical trials to define this hypothesized relationship. Should these further studies confirm an association between HBV/HCV infection and PAC, screening programs might be justified in patients with active or previous hepatitis B and C viral infection.

10. Gorini G, Carreras G, Giordano L, Anghinoni E, Iossa A, Coppo A, Talassi F, Galavotti M, Chellini E. The Pap smear screening as an occasion for smoking cessation and physical activity counselling: effectiveness of the SPRINT randomized controlled trial. BMC Public Health. 2012 Sep 5;12(1):740. [Epub ahead of print]

Abstract
ABSTRACT: BACKGROUND: The organized Cervical Cancer Screening Programme (CCSP) in Italy might represent an occasion to deliver smoking cessation (SC) counselling to women attending the Pap test examination. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to SC counselling is not strong.Objective of the SPRINT trial was to evaluate the effectiveness of a standard SC counselling intervention delivered by trained midwives in the CCSP, and whether the adjunct of a PA counselling to the SC counselling might increase quit rates. METHODS: We undertook a randomized controlled trial of 1,100 women undergoing the Pap examination in the three study centres (Florence, Turin, Mantua): 363 were randomly assigned to the SC counselling arm, 366 to the SC + PA counselling arm, and 371 to the control group. The intervention was a standard brief SC counselling combined with a brief counselling on increasing PA, and was tailored according to the Di Clemente-Prochaska motivational stages of change for SC and/or PA. Primary outcomes were quit rates, improvement in the motivational stages of change for SC, and reduced daily cigarette consumption. Analysis was by intention to treat; RESULTS: Participants randomized in both intervention arms and in the preparation stage of change for SC doubled their likelihood of quitting at 6-month follow-up in comparison to controls (odds ratio [OR]=2.1, 95% confidence interval [95%CI]:1.0-4.6). Moreover, participants in the intervention arms and in the contemplation stage were more likely to reduce their daily cigarette consumption after the intervention (OR=1.8, 95%CI:1.1-3.0). Our study did not show any effect of PA counselling on various outcomes; CONCLUSIONS: Smoking cessation counselling delivered by midwives to smokers in preparation and contemplation stages of change during the Pap-smear screening was effective and should be recommended, given the high number of women attending the cervical cancer screening programme in Italy. Moreover, the daily number of women invited for the Pap-smear examination should be slightly lowered, in order to let midwives deliver SC counselling to smokers.T rial registrationCurrent Controlled Trials ISRCTN52660565.

11. Rubeca T, Peruzzi B, Confortini M, Rapi S. Overall evaluation of an immunological latex agglutination system for fecal occult blood testing in the colorectal cancer screening program of Florence. Int J Biol Markers. 2012 Oct 8;27(3):e195-202. doi: 10.5301/JBM.2012.9343.
Cancer Prevention and Research Institute (ISPO), Florence - Italy.

Abstract
Several immunological fecal occult blood tests (FOBT) are currently available for colorectal cancer (CRC) screening. We compared the HM Jack (Jack) (Kiowa, Japan), with the OC-Hemodia (OC) (Eiken, Japan) in use in the Florence screening program. Aims of the study were: (i) to investigate the diagnostic performance and the best cutoff value for Jack; (ii) to evaluate the handiness of sampling tubes; (iii) to compare costs. A total of 5,044 subjects were screened with both tests. Sampling tube investigation was performed running each sample on both instruments. A number of 352 subjects positive for at least one test (175 OC, 310 Jack) were selected for further investigations, while 46 subjects refused further assessments. Analysis of costs related to the assessment phase was performed on the basis of Tuscany region's fares. Amongst the 306 subjects investigated, 9 CRC and 67 advanced adenomas (AdA) were detected. Detection rates (DR) were 1.4‰ for CRC and 9.6‰ for AdA. After Jack cutoff optimization, DR for CRC+AdA resulted in 11.1‰ for OC and 13.3‰ for Jack (p=0.041). Sensitivity of the methods was 73.7 for OC and 88.2 for Jack; specificity was 97.6 for OC and 96.0 for Jack, resulting in an increase of the required assessments from 3.5% to 5.1%. No differences were observed between sampling methods. Despite the lower specificity of Jack, its greater sensitivity makes the method attractive for screening programs. An increase of the costs of 30% for every subject investigated for pathological lesion (CRC+AdA) may be thus foreseen.

12. Parente F, Marino B, Ilardo A, Fracasso P, Zullo A, Hassan C, Moretti R, Cremaschini M, Ardizzoia A, Saracino I, Perna F, Vaira D. A combination of faecal tests for the detection of colon cancer: a new strategy for an appropriate selection of referrals to colonoscopy? A prospective multicentre Italian study. Eur J Gastroenterol Hepatol. 2012 Oct;24(10):1145-52. doi: 10.1097/MEG.0b013e328355cc79.
Gastrointestinal Unit, A Manzoni Hospital cColorectal Cancer Screening Unit Community Health Care Centre, Lecco, Italy. f.parente@ospedale.lecco.it

Abstract
INTRODUCTION: Colonoscopy workload for endoscopy services in Western countries is increasing markedly because of the implementation of faecal occult blood-based mass screening programmes against colorectal cancer (CRC). We therefore explored the possibility of using a combination of faecal tests to prioritize the access to colonoscopy with criteria other than symptoms and/or time of referral. AIMS AND METHODS: We tested a combination of faecal tests [immunochemical faecal occult blood test (i-FOBT), M2-PK, calprotectin] as markers for advanced neoplasia in a selected series of patients requiring colonoscopy for the suspicion of CRC. All the tests were performed in a 1-day stool sample of patients aged 50-80 years, without any dietary restriction, before colonoscopy. RESULTS: A total of 280 patients' stool single samples were analysed. Forty-seven patients had CRC and 85 patients had one or more advanced adenoma(s) at colonoscopy/histology. CRCs were associated with a highly significant increase (P<0.001) in faecal tumour M2-PK (mean 24.2 kU/l), which correlated with Dukes' staging. For CRC detection, i-FOBT was the test with the highest specificity and positive predictive value (0.89 and 0.53), whereas M2-PK had the highest sensitivity and negative predictive value (0.87 and 0.96). Calprotectin showed performance similar to M2-PK in terms of sensitivity and negative predictive value (0.93), but had lower specificity (0.39). The best combination of tests to predict the risk of CRC in this series was i-FOBT+M2-PK, as in patients showing positivity to both markers, the risk of cancer was as high as 79%. CONCLUSION: The combination of i-FOBT and M2-PK is a sensitive tool in clinical practice for the appropriate management of waiting lists for colonoscopy, as it allows the classification of patients into different degrees of priority for investigation, according to their foreseeable risk of CRC.

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