rubrica

Screening

  • Paolo Giorgi Rossi1

  1. Servizio interaziendale di epidemiologia, AUSL Reggio Emilia

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Ricerca bibliografica periodo dal 16 giugno 2013 al 30 agosto 2013

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 ("2013/06/16"[PDAT] : "2013/08/30"[PDAT])

Breve commento a cura di P. Giorgi Rossi
In questo periodo estivo sono usciti 11 lavori che parlano di screening prodotti da gruppi italiani. Gli argomenti trattati presentano alcune novità: non ci sono lavori sullo screening mammografico, solo uno sul colon retto (Parente), mentre 5 sono sulla cervice (Liverani, Zucchetto, Dalla Palma, Zorzi, Favato), due sulla prostata (Penney, Chiriacò) e uno rispettivamente su polmone (Lopez-Pegna), carcinoma anale in maschi omosessuali (Donà), e vescica (Martini). Lo studio sul colon retto (Parente) mostra ancora una volta come i programmi di screening siano una fonte di casistica population based di fondamentale importanza per la ricerca epidemiologica e clinica. Gli studi sulla cervice sono estremamente eterogenei: due valutazioni economiche, una della lettura computer assistita del Pap test (Dala Palma), una del vaccino (Favato) che presenta una interessante innovazione metodologica; Zorzi presenta i risultati di un ampio studio pilota sull’uso del test HPV come test primario in Veneto, sono dati molto attesi e che integrano le prove di efficacia date dai trial, con informazioni sulla effectiveness, sulla fattibilità e sull’accettabilità da parte delle utenti in contesti routinari; Liverani presenta un punto di vista di un clinico molto attento alla sanità pubblica e pone al’attenzione tutti i suoi dubbi sulle trasformazioni dello screening, insistendo, giustamente sulla priorità di aumentare le coperture; infine una lettera presenta qualche dato in più sul’analisi di sopravvivenza nello studio IMPATTO. Dei due studi sulla prostata, uno presenta i risultati di accuratezza di un test simultaneo per PSA totale e Free (Chiriacò), l’altro (Penney) propone un’interessante analisi del ruolo del Glison come marcatore prognostico indipendente dallo stadio, qualcosa che nello screening della prostata potrebbe veramente fare la differenza spezzando il legame fra sovra-diagnosi e sovra-trattamento, certo sembra difficile che la soluzione fosse lì e nessuno l’avesse trovata… studi prospettici e analisi delle coorti gestite con “careful watch” non hanno dato risultati altrettanto promettenti. Lo studio sul polmone (Lopez-Pegna) presenta dati preliminari dello studio ITALUNG, ancora niente di veramente rilevante sull’efficacia. Lo studio sul carcinoma anale introduce una tematica importante: il test HPV può diventare un’opportunità per screenare gruppi ad altro rischio per carcinomi in altre sedi oltre alla cervice. Infine, un lavoro (Martini) presenta i risultati di modelli predittivi del rischio di avere un carcinoma della vescica, il valore predittivo positivo del modello risulta del 67%, un valore alto se fossimo in una popolazione di screening (in gran parte sana), ma il modello è stato validato su di una popolazione di 241 persone di cui 141 con carcinoma della vescica, dunque ance il lancio di una monetina avrebbe avuto un valore predittivo positivo del 60%! Forse l’ottimismo degli autori è un po’ eccessivo.

1. Parente F, Bargiggia S, Boemo C, Vailati C, Bonoldi E, Ardizzoia A, Ilardo A, Tortorella F, Gallus S. Anatomic distribution of cancers and colorectal adenomas according to age and sex and relationship between proximal and distal neoplasms in an i-FOBT-positive average-risk Italian screening cohort. Int J Colorectal Dis. 2013 Aug 24. [Epub ahead of print]
Gastroenterology Unit, Department of Oncology, A.Manzoni Hospital, Via dell'Eremo 9/11, 23900, Lecco, Italy, f.parente@ospedale.lecco.it.

Abstract
BACKGROUND AND AIMS: Subsite-specific incidence rates of colorectal cancer (CRC) and adenomas may vary considerably by race, sex and age as well as due to different screening strategies. We assessed variations in the anatomical distribution of adenomas according to age and sex in an average-risk screening cohort testing positive at immunological faecal occult blood test (i-FOBT) in northern Italy. METHODS: Data from 2,281 consecutive asymptomatic i-FOBT-positive subjects ageing 50-70 years undergone colonoscopy were reviewed. Size, number, macroscopic and histological features of all adenomas found as well as their proximal or distal location in relation to the splenic flexure were examined. Odds ratios (OR) of proximal neoplasms, according to the presence of distal neoplasms and other selected covariates were assessed by multiple logistic regression analysis. RESULTS: A total of 2,599 neoplasms were found in 1,396 patients. Of these, 116 (5 %) were colorectal cancers, diagnosed in 106 patients. Out of 2,483 adenomas found, 1,564 (63 %) were sessile, 795 (32 %) were peduncolated and 124 (5 %) were flat-type; 54 % of all adenomas were tubular, 36 % were tubulovillous or villous, and 10 % were serrated adenomas. The majority of neoplasms (66 %) were located in the distal colon. Tumour subsite distribution was consistent in both sexes, whereas significant proximal migration of neoplasms occurred in the older age cohort. Indeed, the rate of proximal neoplasms in patients aged ≥60 years was 37 % as compared with 29 % in those ageing 50-59 years. Male gender (OR 1.84), age of 60 years or older (OR 1.44), having a family history of colorectal neoplasms (OR 1.47) and presence of at least 1 distal advanced adenoma (OR 1.63) were all significant predictors of advanced proximal neoplasms. CONCLUSIONS: A left to right shift of colorectal adenomas with increasing age is evident in northern Italian asymptomatic i-FOBT-positive population. Advanced proximal neoplasms are not uncommon in subjects with or without distal adenomas, especially after 60 years of age. This should be carefully considered when implementing public screening strategies for CRC since the use of flexible sigmoidoscopy as a screening tool, particularly in older age groups, appears to be less effective.

2. Liverani CA. The four steps in the prevention of human papillomavirus-associated neoplasia : Considerations for preventive measures, screening, disease impact, and potential overtreatments in HPV-related pathology. Arch Gynecol Obstet. 2013 Aug 24. [Epub ahead of print]
Gynecologic Oncology Unit, Department of Mother and Infant Sciences, University of Milan, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, dr.carlo.liverani@gmail.com.

Abstract
There is no cure currently available for HPV infections, although ablative and excisional treatments of some dysplasias often result in a clinical and virological cure. Effective control measures of HPV-associated cancers rely on the prevention at four different levels. Apart from sexual abstinence, primary prevention is realized through vaccines targeting the most frequent HPV types: negative attitudes towards HPV vaccination and high costs are the main obstacles. The aim of secondary prevention is to detect precancerous changes before they develop into invasive cancer, while tertiary prevention involves actual treatment of high-grade lesions: in many countries routine screening with cytology is being challenged with HPV DNA testing. Quaternary prevention comprehends those actions adopted to mitigate or avoid unnecessary or excessive medical interventions, and may well be addressed in avoiding treatments for low-grade intraepithelial neoplasia. Though some gynecologists commonly recommend treatment for low-grade disease and women tend to prefer active management if not properly informed, harms arising from unnecessary treatments, increased costs, work overload for second-level health services, and induced psychosocial distress are causing on-going problems. Prevention efforts of genital HPV-associated cancers should concentrate in: (1) enhancing primary prevention through vaccination of all eligible subjects, (2) achieving high levels of adherence to routine screening programs, (3) treating precancerous lesions, and (4) monitoring current guidelines recommendations to avoid overtreatments. Novel research projects should be designed to study the delicate mechanisms of immune response to HPV.

3. Zucchetto A, Ronco G, Rossi PG, Zappa M, Serraino D; Reply to manuscript no. 13-479, Dugué et al. - Re: Lead time and down-staging in the survival of cervical cancer cases detected by screening. Prev Med. 2013 Aug 14. pii: S0091-7435(13)00283-1. doi: 10.1016/j.ypmed.2013.08.006. [Epub ahead of print]
Epidemiology and Biostatistics, Aviano National Cancer Institute (CRO), Via Gallini 2, 33081 Aviano (PN), Italy; Clinical Sciences and Community Health, Milan University, Via Vanzetti 5, 20133 Milano, Italy. Electronic address: zucchetto.epi@cro.it.
4. Donà MG, Paolini F, Benevolo M, Vocaturo A, Latini A, Giglio A, Venuti A, Giuliani M. Identification of Episomal Human Papillomavirus and Other DNA Viruses in Cytological Anal Samples of HIV-Uninfected Men Who Have Sex with Men. PLoS One. 2013 Aug 12;8(8):e72228. doi: 10.1371/journal.pone.0072228. eCollection 2013.
Sexually Transmitted Infection (STI) Unit, San Gallicano Dermatological Institute, Rome, Italy.

Abstract
To date, there have been only few studies that investigated integration of anal Human Papillomavirus (HPV). Most of them were conducted on HIV-infected individuals and mainly analyzed samples from high-grade lesions and invasive cancer. We aimed to investigate HPV physical status in HIV-negative men who have sex with men (MSM) with a detectable anal HPV infection, irrespective of the presence of lesions. We also sought to explore the presence of other circular DNA viruses in the anal region. Study participants were attendees of an STI screening program, which were also screened for anal HPV infection and cytological abnormalities. HPV physical status was assessed using multiply-primed RCA. HPV16-positive samples were also analyzed using E2/E6 multiplex PCR, qRT-PCR and APOT assay. RCA and virus-specific PCR were employed to investigate the presence of other DNA viruses. Anal HPV infection was detected in 76.9% of the 230 MSM enrolled. The anal cytological reports were: 129 NILM, 37 ASC-US and 28 L-SIL (36 samples were inadequate for interpretation). HPV physical status was evaluated in the 109 anal specimens that harbored one or two different HPV genotypes. Integration was observed only in one HPV16-positive sample (0.9%), in which integrate-derived viral transcripts of type B were detected. Integration occurred in chromosome 14 q. In 22 of the 53 (41.5%) mucosal HPV-negative samples, RCA restriction results would seem to indicate the presence of circular DNA viruses. Indeed, cutaneous HPV (4 samples), MCPyV (5 samples) and TTV (4 samples) were detected. In conclusion, anal HPV integration was rarely evidenced in HIV-uninfected MSM with no or mild anal cytological abnormalities, although the integration rate may have been underestimated because of the limitations of the employed assays. Other DNA viruses were detected in the anal samples of these individuals, although the significance of this occurrence needs to be assessed.

5. Penney KL, Stampfer MJ, Jahn JL, Sinnott JA, Flavin R, Rider JR, Finn S, Giovannucci E, Sesso HD, Loda M, Mucci LA, Fiorentino M. Gleason Grade Progression Is Uncommon. Cancer Res. 2013 Aug 15;73(16):5163-5168.
Authors' Affiliations: Departments of Epidemiology, Nutrition, and Biostatistics, Harvard School of Public Health; Channing Division of Network Medicine, Department of Medicine; Departments of Preventive Medicine and Pathology, Brigham and Women's Hospital and Harvard Medical School; Department of Pathology, Dana-Farber Cancer Institute, Boston; The Broad Institute, Cambridge, Massachusetts; Department of Histopathology Research, Trinity College, Dublin, Ireland; and Pathology Unit, Addarii Institute of Oncology, University of Bologna, Italy.

Abstract
Gleason grade is universally used for pathologic scoring of the differentiation of prostate cancer. However, it is unknown whether prostate tumors arise well differentiated and then progress to less differentiated forms or if Gleason grade is an early and largely unchanging feature. Prostate-specific antigen (PSA) screening has reduced the proportion of tumors diagnosed at advanced stage, which allows assessment of this question on a population level. If Gleason grade progresses as stage does, one would expect a similar reduction in high-grade tumors. We studied 1,207 Physicians' Health Study and Health Professionals Follow-up Study participants diagnosed with prostate cancer from 1982 to 2004 and treated with prostatectomy. We compared the distribution of grade and clinical stage across the pre-PSA and PSA screening eras. We re-reviewed grade using the ISUP 2005 revised criteria. The proportion of advanced stage tumors dropped more than six-fold, from the earliest period (12/1982-1/1993), 19.9% stage ≥T3, to the latest (5/2000-12/2004), 3% stage T3, none T4. The proportion of Gleason score ≥8 decreased substantially less, from 25.3% to 17.6%. A significant interaction between stage and diagnosis date predicting grade (P = 0.04) suggests that the relationship between grade and stage varies by time period. As the dramatic shift in stage since the introduction of PSA screening was accompanied by a more modest shift in Gleason grade, these findings suggest that grade may be established early in tumor pathogenesis. This has implications for the understanding of tumor progression and prognosis, and may help patients diagnosed with lower grade disease feel more comfortable choosing active surveillance.

6. Chiriacò MS, Primiceri E, Montanaro A, de Feo F, Leone L, Rinaldi R, Maruccio G. On-chip screening for prostate cancer: an EIS microfluidic platform for contemporary detection of free and total PSA. Analyst. 2013 Sep 21;138(18):5404-10. doi: 10.1039/c3an00911d. Epub 2013 Jul 25.
NNL Istituto Nanoscienze - CNR and Dipartimento di Matematica e Fisica "Ennio De Giorgi", Università del Salento, Lecce, Italy. serena.chiriaco@unisalento.it giuseppe.maruccio@unisalento.it.

Abstract
Prostate cancer affects a large part of the western male population. The need for an early and accurate detection is thus a great challenge in common clinical practice, but the lack of specificity of the serum marker PSA (Prostate Specific Antigen) is a serious problem since its increased concentration can be related to several abnormalities. PSA, however, is found in serum in both a free and a complexed form with other proteins and the percentage amount of unbound PSA (the free-to-total PSA ratio) can be employed to distinguish prostate cancer from benign prostatic conditions, and also to predict the future risk of prostate cancer. To improve the operating characteristics of current PSA tests and to provide a clinical tool able to run label-free and sensitive analysis, we thus developed a biosensing platform based on Electrochemical Impedance Spectroscopy (EIS), which allows the contemporary detection of free and total PSA on a single biochip, enabling a quick screening for the risk of prostate cancer thanks to the presence of two different immobilized antibodies specific for the different antigens researched.

7. Martini T, Mayr R, Lodde M, Seitz C, Trenti E, Comploj E, Palermo S, Pycha A, Mian C, Zywica M, Weidner W, Lüdecke G. Validation of RiskCheck Bladder Cancer ©, Version 5.0 for Risk-Adapted Screening of Bladder Cancer. Urol Int. 2013 Jul 16. [Epub ahead of print]
Department of Urology, General Hospital of Bolzano, Bolzano, Italy.

Abstract
Introduction: The aim of the study was to assess the strength of the online tool RiskCheck Bladder Cancer©, version 5.0 (RCBC) for early detection of bladder cancer (BC). Materials and Methods: RCBC was evaluated retrospectively based on the data of 241 patients, of which 141 were suffering from BC. Statistical analysis was performed by descriptive statistics, nonparametric group comparison, classification tree analysis and ROC analysis. Results: ROC analysis of the risk classification showed a sensitivity of 71.6%, a specificity of 56.5%, a positive predictive value of 67.8%, a negative predictive value of 52% and an accuracy of 63.5%. BC risk factors ranked by importance are time of smoking (p < 0.0001), gender (within the nonsmoking group: p < 0.009), occupational toxin exposure (within the group <35 years of smoking: p < 0.048) and amount of consumed cigarettes resulting in a 95% association with BC (within the group >35 years of smoking: p < 0.0001). Conclusions: The high predictive power of RCBC for the identification of asymptomatic patients living under risk could be demonstrated.

8. Dalla Palma P, Moresco L, Giorgi Rossi P. Health technology assessment of computer-assisted pap test screening in Italy. Acta Cytol. 2013;57(4):349-58. doi: 10.1159/000351167. Epub 2013 Jul 12.
Anatomia Patologica, Ospedale S. Chiara, Trento, Italy.

Abstract
Objective: To assess the introduction of computer-assisted Pap test screening in cervical cancer screening. Various scenarios are considered: conventional and liquid-based cytology (LBC) slides, fully automatic instrumentation (Becton Dickinson FocalPoint™ Slide Profiler and Hologic ThinPrep® Imaging System), and semiautomatic scanner (Hologic Integrated Imager I-Squared). Methods: A working group was formed that included researchers from the largest centers already using instrumentation. A questionnaire on laboratory management and on social/ethical issues and annual workload was proposed. Prices for the technology were obtained directly from the producers; costs were calculated from observed and literature data. The scope of the report and final draft were submitted to a consulting committee of stakeholders. Results: The break-even point was found to be 49,000 cases/year, if conventional slides were used, while it was near the theoretical maximum capacity, 70,000 cases/year, with LBC slides. Efficiency increased with the volume of slides. Screening time decreased by two thirds for conventional slides and by less than half for LBC slides. Acceptance of the instrumentation by the users was good. Conclusions: Computer-assisted screening may increase productivity even if in most situations it will mean additional costs. Furthermore, primary screening with human papillomavirus tests will drastically reduce the need for Pap test reading.

9. Favato G, Baio G, Capone A, Marcellusi A, Saverio Mennini F. A novel method to value real options in health care: the case of a multicohort human papillomavirus vaccination strategy. Clin Ther. 2013 Jul;35(7):904-14. doi: 10.1016/j.clinthera.2013.05.003. Epub 2013 Jun 24.
Institute of Leadership and Management in Health, Kingston University, London, United Kingdom. Electronic address: g.favato@kingston.ac.uk.

Abstract
BACKGROUND: A large number of economic evaluations have already confirmed the cost-effectiveness of different human papillomavirus (HPV) vaccination strategies. Standard analyses might not capture the full economic value of novel vaccination programs because the cost-effectiveness paradigm fails to take into account the value of active management. Management decisions can be seen as real options, a term used to refer to the application of option pricing theory to the valuation of investments in nonfinancial assets in which much of the value is attributable to flexibility and learning over time. OBJECTIVE: The aim of this article was to discuss the potential advantages shown by using the payoff method in the valuation of the cost-effectiveness of competing HPV immunization programs. METHODS: This was the first study, to the best of our knowledge, to use the payoff method to determine the real option values of 4 different HPV vaccination strategies targeting female subjects aged 12, 15, 18, and 25 years. The payoff method derives the real option value from the triangular payoff distribution of the project's net present value, which is treated as a triangular fuzzy number. To inform the real option model, cost-effectiveness data were derived from an empirically calibrated Bayesian model designed to assess the cost-effectiveness of a multicohort HPV vaccination strategy in the context of the current cervical cancer screening program in Italy. A net health benefit approach was used to calculate the expected fuzzy net present value for each of the 4 vaccination strategies evaluated. RESULTS: Costs per quality-adjusted life-year gained seemed to be related to the number of cohorts targeted: a single cohort of girls aged 12 years (€10,955 [95% CI, -1,021 to 28,212]) revealed the lowest cost among the 4 alternative strategies evaluated. The real option valuation challenged the cost-effectiveness dominance of a single cohort of 12-year-old girls. The simultaneous vaccination of 2 cohorts of girls aged 12 and 15 years yielded a real option value (€17,723) equivalent to that attributed to a single cohort of 12-year-old girls (€17,460). CONCLUSIONS: The payoff method showed distinctive advantages in the valuation of the cost-effectiveness of competing health care interventions, essentially determined by the replacement of the nonfuzzy numbers that are commonly used in cost-effectiveness analysis models, with fuzzy numbers as an input to inform the real option pricing method. The real option approach to value uncertainty makes policy making in health care an evolutionary process and creates a new "space" for decision-making choices.

10. Zorzi M, Del Mistro A, Farruggio A, De' Bartolomeis L, Frayle-Salamanca H, Baboci L, Bertazzo A, Cocco P, Fedato C, Gennaro M, Marchi N, Penon M, Cogo C, Ferro A. Use of a high-risk human papillomavirus DNA test as the primary test in a cervical cancer screening programme: a population-based cohort study. BJOG. 2013 Sep;120(10):1260-8. doi: 10.1111/1471-0528.12272. Epub 2013 Jun 21.
Veneto Tumour Registry, Istituto Oncologico Veneto IRCCS, Padua, Italy.

Abstract
OBJECTIVE: To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. DESIGN: Population-based cohort study. SETTING: A cervical service screening programme in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to April 2011. METHODS: Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). CONCLUSIONS: Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.

11. Lopes Pegna A, Picozzi G, Falaschi F, Carrozzi L, Falchini M, Carozzi FM, Pistelli F, Comin C, Deliperi A, Grazzini M, Innocenti F, Maddau C, Vella A, Vaggelli L, Paci E, Mascalchi M; ITALUNG Study Research Group. Four-year results of low-dose CT screening and nodule management in the ITALUNG trial. J Thorac Oncol. 2013 Jul;8(7):866-75. doi: 10.1097/JTO.0b013e31828f68d6.
Pneumonology Department, Careggi Hospital, Florence, Italy.

Abstract
INTRODUCTION: Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography (LDCT). We report subjects' compliance and results of LDCT screening and management protocol in the active arm of the ITALUNG trial. METHODS: Three thousand two hundred six smokers or former smokers invited by mail were randomized to receive four annual LDCT (n = 1613) or usual care (n = 1593). Management protocol included follow-up LDCT, 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB). RESULTS: One thousand four hundred six subjects (87%) underwent baseline LDCT, and 1263 (79%) completed four screening rounds. LDCT was positive in 30.3% of the subjects at baseline and 15.8% subsequently. Twenty-one lung tumors in 20 subjects (1.5% detection) were found at baseline, and 20 lung tumors in 18 subjects (0.5% detection) in subsequent screening rounds. Ten of 18 prevalent (55%) and 13 of 17 incident (76%) non-small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects (42%), but at least one follow-up LDCT was obtained in 741 subjects (52.7%) over the screening period. FDG-PET obtained in 6.5% of subjects had 84% sensitivity and 90% specificity for malignant lesions. FNAB obtained in 2.4% of subjects showed 90% sensitivity and 88% specificity. Positivity of both FDG-PET and FNAB invariably predicted malignancy. Surgery for benign lesions was performed on four subjects (10% of procedures) but followed protocol violations on three subjects. CONCLUSIONS: High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance. Efficacy of screening is, however, weakened by low detection rate and specificity. Adhesion to management protocol might lessen surgery for benign lesions.

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