Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Patient presentation, skin biopsy utilization and cutaneous malignant melanoma incidence and mortality in northern Italy: Trends and correlations.

BACKGROUND: The global increase in incidence of cutaneous malignant melanoma (CMM) occurring in the past decades has been partly attributed to increased diagnostic scrutiny of early lesions, with a potential phenomenon of overdiagnosis. The reported positive linear relation between skin biopsy rate and incidence of early CMM is compatible with this hypothesis. OBJECTIVES: We explored the ecological association between the trends in annual dermatologic office visit rates, skin biopsy rates, incidence rates of in situ and invasive CMM by tumour thickness category, and CMM mortality rates in the Emilia-Romagna Region (northern Italy). METHODS: Four cancer registries covering a population of 2,696,000 provided CMM incidence data for the years 2003-2017. Dermatologic office visit rates and skin biopsy rates were calculated using the Regional outpatient care database. All rates were age-standardized. Trends were described with the estimated average annual per cent change (EAAPC). Correlations were tested with the Spearman correlation coefficient. RESULTS: Incidence increased significantly. The increase was steeper for in situ CMM (EAAPC: men, 10.2; women, 6.9) followed by CMM <0.8 mm thick (9.1; 5.2), but the rates grew significantly for most subgroups of CMMs ≥0.8 mm thick. Mortality decreased significantly among women (-2.3) and non-significantly among men. For dermatologic office visit rate and skin biopsy rate the EAAPC were, respectively, 1.7 and 1.8 for men and 1.2 and 0.9 for women. Annual dermatologic office visit rate correlated with skin biopsy rate in both sexes. However, the proportion of skin biopsies out of dermatologic office visits was constant across the years (range: men, 0.182-0.216; women, 0.157-0.191). CONCLUSIONS: In Italy, the increasing CMM incidence trend is, at least in part, genuine. Overdiagnosis-if any-is due to an increased patient presentation at dermatologic offices and not to a lower dermatologic threshold to perform biopsy.

The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population-based investigation.

BACKGROUND: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor. OBJECTIVES: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy. METHODS: Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors. RESULTS: Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017. CONCLUSIONS: For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

[Update of survival of cancer patients in Italy: geographical comparisons and focus on patients with cancers targeted by screening programmes, childhood cancers, and smoking-associated cancers]. / Aggiornamento della sopravvivenza dei pazienti con tumore in Italia: confronti geografici e focus su pazienti con tumori oggetto di screening, pediatrici e associati al fumo.

OBJECTIVES: to update the Italian estimates of survival for patients with a paediatric cancer, tobacco smoke-associated cancers, and cancers targeted by screening; to assess geographical differences. DESIGN: population-based descriptive study. SETTING AND PARTICIPANTS: incident cancer cases diagnosed in 2010-2014, with follow-up to 2018, from 17 Italian cancer registries (covering 31% of the national population; 43% of the population residing in the North-Centre of the country and 8% of the population living in the South and Islands). MAIN OUTCOME MEASURES: age-standardized 5-year net survival (NS) by cancer site or type, sex, age, and geographical area. RESULTS: NS of patients aged ≥15 years with breast, prostate, colorectal, and lung cancers was higher in the North-Centre than in the South and Islands. The overall survival of people diagnosed with cancer in childhood (0-14 years) was 84.3%, with similar values among the geographical macro-areas and between males and females. Women with breast cancer within the current target age of the screening programmes and those in the younger age groups (45-49 years) show similar survival values; the same is true for women with colorectal cancer. In both cases, survival decreased in the age groups after the age of cessation of screening programmes. Survival of patients with tobacco smoke-associated cancers varies according to cancer site (from 11.1% for patients with pancreatic cancer to 79.7% for those with bladder cancer). For most cancer sites, women have higher survival than men. CONCLUSIONS: for adults, a geographical survival gap persists. The results may contribute to the debate on extending the target age for screening programmes and to support initiatives to encourage tobacco smoking cessation even after cancer diagnosis. For patients who receive a cancer diagnosis in childhood, survival similar to highest values internationally.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

T-PEC: a novel test for the elicited production of clitic pronouns in Italian. Preliminary data.

The study presented in this article aims at investigating the clinical usefulness of a novel test, called T-PEC, for the diagnosis of Developmental Language Disorder in Italian preschool children. The instrument exploits the production of clitic pronouns, in particular third person direct object clitics (3PDO-CL), as a clinical marker for the disorder. Psychometric properties and normative data were computed on a sample of 70 children ranging in age from 4.6 to 5.8 years: 22 children diagnosed as language-impaired by expert clinicians according to international guidelines, and 48 typically developing peers. The statistical analysis of the collected data revealed good internal consistency (Cronbach's α = 0.86) and confirmed the effectiveness of the T-PEC test in distinguishing typically developing and DLD children, especially when the latter showed morphosyntactic deficits (AUC = 79.9%). Its high accuracy, combined with the rapidity and easiness of its administration, makes the T-PEC test suitable for use in clinical settings.

[Perception of the conflict of interest in people working in public health services]. / Percezione dell'esistenza di un conflitto di interessi in chi opera in strutture di sanità pubblica.

BACKGROUND: the employment relationship with a public health service foresees a remuneration that in many cases is the main income, it takes place within a hierarchical structure, whose top management is nominated by politics. Therefore, objectives and priorities can change according to the prevailing policy. OBJECTIVES: to verify the existence of the perception of a potential conflict of interest in the employment relationship with a public health service. DESIGN: descriptive study. SETTING E PARTICIPANTS: authors of the papers published in the years 2016-2017 in Epidemiologia&Prevenzione (E&P). MAIN OUTCOME MEASURES: numbers of authors and of declarations of conflict of interest. RESULTS: in the 12 issues published by E&P in the two years under review, 144 contributions, drawn up by 630 authors, were evaluated; 16% of the contributions did not have the declaration of conflict of interest; the authors declared the existence of some conflict of interest in 10 contributions (6.9%). Thirteen of the 630 authors (2.0%) declared a conflict. Two of these declarations (2/630; 0.3%) referred to their employment relationship. CONCLUSIONS: This context does not seem to foster the independence of thought: only 0.3% of the authors indicated the working relationship among their conflicts of interest. In general, the declaration of the conflict of interest involved 2% of the authors. The need to discuss the conflict of interest, its awareness and its control should be a priority action of the scientific community, scientific associations, and scientific journals.

[Reporting a cluster of lymphohaematopoietic cancers and management of the communication process with the community: the experience of a Local health Authority in Tuscany, Italy]. / Segnalazione di un cluster di neoplasie emolinfopoietiche e gestione del processo di comunicazione con la cittadinanza: l'esperienza di una Asl toscana.

In 2008, some general practitioners (GPs) in the area of Empoli (Tuscany Region, Central Italy), reported to the Local Health Authority (LHA), an unusually high frequency of leukemia deaths among their patients residing in a one of the municipalities of the area. The LHA decided to carry out an epidemiological investigation. An interdepartmental working group was set up, led by the Department of Prevention of the LHA, and made up of representatives of the Institute for Study, Prevention and Cancer Network (ISPRO, Florence), the G. Monasterio Foundation/ Institute of Clinical Physiology of the National Council for Research (CNR) of Pisa, the University of Pisa, the Regional Environmental Protection Agency and community members. Several epidemiological analyses were carried out (namely incidence and mortality analysis, assessment of the residential history of all cases and micro-geographical incidence evaluation, assessment and quantification of local environmental pressures, evaluation of congenital abnormalities). The investigation took over two years to be completed. The work agenda was shared with community members, who contributed to decision-making, study design and the communication plan. Thanks to the interaction with community members, researchers had the chance to become aware of their information needs and of local knowledge concerning the research issues. The final report was published online and presented to citizens in several public meetings. Direct involvement of the local community during project development was found to be useful to reduce the perceived distance between public authorities and the local population, as highlighted in the guidelines on cancer cluster investigations.

[The contribution of the Italian association of cancer registries (AIRTUM)]. / Il contributo dell'Associazione italiana dei registri tumori (AIRTUM).

The study of cluster requires the ability to identify, with accuracy and completeness, the health events of interest and their geographical location and time of occurrence. For rare and complex diseases, such as childhood cancers, it is possible to observe a significant health migration from the place of residence, which makes the detection even more complex. The best tool to identify these rare diseases is represented by cancer registries (CRs). In fact, CRs collect, through many sources, information related to tumours that arise in the population resident in their areas of activity. The number of the sources of information has increased thanks to the computerization of health services. The availability of multiple sources of information increases the completeness of data collection overcoming the limits of a single source, and makes it possible to describe the diagnostic-therapeutic course and the outcome of the cases. Among all data sources, for childhood cancers the model 1.01, which summarize the clinical information of the cases treated in one of the Italian Association of paediatric haematology and oncology (AIEOP) centres, is relevant. Moreover, CRs produce reliable and comparable data due to the use of international rules and classifications for the definition of the topography and morphology of cancer, for the date of diagnosis, and for quality checks. In Italy, the Italian association of cancer registries (AIRTUM) coordinates the activities of 45 population CRs, both general and specialized (by age or tumour type). AIRTUM involves a population of over 6.7 million citizens under the age of 20 years, approximately 60% of the total resident population. AIRTUM plays a role of coordination, support, and harmonization for Italian CRs through training, accreditation, and a shared database, it promotes and participates in national and international collaboration involving scientific societies (AIEOP, Italian Association of medical oncology - AIOM, Italian Federation of volunteer-based cancer organisations - FAVO) and institutions (Italian national Institute of health, Italian national cancer institute of Milan) and performs analysis on key epidemiological indicators (incidence, mortality, survival, and prevalence). The AIRTUM database contains 19,650 cancer cases in child/ adolescent patients diagnosed from 1967 to 2011. The epidemiology of childhood cancers has been the subject of two AIRTUM monographs published in 2008 and in 2013 in collaboration with AIEOP; the latter includes specific contributions on polluted sites, on the psychological side, and on the experience of the parents of young cancer patients. The collaboration between different professionals, needs, and knowledge is the policy followed by AIRTUM to build up a complete picture of cancer epidemiology, even of childhood cancer, in Italy.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Changes in cervical cancer incidence following the introduction of organized screening in Italy.

OBJECTIVE: To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs. METHODS: This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium. RESULTS: ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%). CONCLUSION(S): Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.

Incidence of infection-associated cancers in Italy and prevention strategies.

Chronic infections and infestations represent major causes of cancer. Overall, Helicobacter pylori, HPV, HBV, and HCV are estimated to account for 15% of all human cancers. We have estimated that cancers associated with 6 pathogens in Italy account for 31,000 yearly cases, 42.0%of which is attributable to H. pylori, 34.7%to HBV and HCV, 19.8%to HPV, 2.9%to KSHV, and 0.2% to EBV. These figures represent 8.5% of all incident cases of cancer in Italy. The implementation of anti-HBV vaccination programs in countries with high endemicity resulted in a significant impact on the incidence of hepatocellular carcinoma, and the availability of antiviral drugs is a real opportunity to drastically reduce the cases attributable to HCV. Primary prevention of cervical cancer mainly involves HPV vaccination; two vaccines (bivalent and quadrivalent) are available and a new vaccine (9-valent) has recently been approved by the FDA. Secondary prevention is based on screening programs that include Pap smear cytology and/or HPV test. To reduce the burden of HIV-associated cancers, prevention programs include primary prevention of HIV infection, early diagnosis and treatment, restoration of immune function, reduction in the prevalence of associated infections and risk factors, and secondary prevention. To date, anti-HBV and anti-HPV vaccinations, eradication of H. pylori infection, treatment of HCV and HIV carriers with antivirals, and HPV-related cancer screening prove to be the most effective strategies for the prevention of infection-associated cancers.

Problems, solutions, and perspectives in the evaluation of interval cancers in Italian mammography screening programmes: a position paper from the Italian group for mammography screening (GISMa).

In this position paper, a self-convened team of experts from the Italian Group for Mammography Screening (Gruppo italiano screening mammografico, GISMa) pointed out the problems that increasingly hamper the feasibility and validity of the estimate of the proportional incidence of interval breast cancer (IBC) in Italy, suggested potential solutions and an agenda for research, and proposed that the question of the sensitivity of mammography be viewed in a larger perspective, with a greater attention to radiological review activities and breast radiology quality assurance programmes. The main problems are as follows: the coverage of cancer registration is incomplete; the robustness of using the pre-screening incidence rates as underlying rates decreases with time since the start of screening; the intermediate mammograms performed for early detection purposes may cause an overrepresentation of IBCs; the classification of many borderline screening histories is prone to subjectivity; and, finally, the composition of cohorts of women with negative screening results is uncertain, because several mammography reports are neither clearly negative nor clearly positive, and because of the limitations and instability of the electronic mammography records. Several possibilities can be considered to cope with these issues: standard methods for using the hospital discharge records in the identification of IBCs should be established; for the calculation of regional estimates of the underlying incidence, a suitable mathematical model should be identified; the definition of IBC according to the 2008 GISMa guidelines needs to be updated, especially with respect to in situ cancers and to invasive cancers with borderline screening histories; a closer adherence to standard screening protocols, with a simplified patient management, would make it easier to objectively identify IBCs; alternative methods for estimating the sensitivity of mammography should be taken into consideration; and, finally, analysis could be restricted to the absolute incidence rate of IBC, which would make comparison of the risk between neighbouring populations possible. Epidemiologists must extend their attention to the prevention of the risk of IBC and the implementation of breast radiology quality assurance practices. Epidemiologists and radiologists can share common objectives: it is necessary to promote the idea that the availability of a registry-based series of IBCs is not a prerequisite for their radiological review; radiological review of breast cancers greater than 20mm in size detected at second and subsequent screens, that are potential substitutes for IBCs, needs radiological and epidemiological validation studies; the advent of digital mammography brings about the possibility to create libraries of mammograms accessible online, which enables the conduct of large studies of the diagnostic variability of radiologists; and, finally, epidemiologists and radiologists have the responsibility to monitor the effects that a loss of cumulative professional experience in screening centres, due to the imminent retirement of a substantial proportion of healthcare workforce, could cause on their performance.

[Risk profiling in cancer surveillance in contaminated sites: an example from the ISS-AIRTUM collaborative study]. / Sintesi del profilo di incidenza di tumore nei SIN: un esempio dallo studio collaborativo ISS-AIRTUM.

Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.

[SENTIERI KIDS: monitoring children's health in Italian polluted sites]. / SENTIERI KIDS: monitorare lo stato di salute infantile nei siti inquinati in Italia.

Protecting children's health from the effects of environmental contamination is a public health priority. In recent years, particular care has been devoted in Italy to the study of the relationship between environmental pollutants and health during infancy. The SENTIERI Project has called attention to increases in infant mortality in National Priority Contaminated Sites (NPCSs). SENTIERI KIDS provides a blueprint for the establishment of a task force charged with establishing multi and inter-disciplinary cooperation between central and regional institutions on the subject of children's health in contaminated sites. SENTIERI KIDS introduces a multiple outcome analytical model based on updated health outcomes (mortality, cancer incidence, hospital discharges) in order to establish a permanent observation system to monitor the state of health of infants residing in contaminated areas. This will pave the way for more in-depth epidemiological enquiries on an individual basis, and support the establishment and continued monitoring of primary prevention projects. Particular attention is devoted to issues of information and communication.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

The Istituto Superiore di Sanità (National Institute of Health-ISS), in partnership with a network of Italian national and regional scientific institutions, initiated the SENTIERI Project (Epidemiological Study of Residents in Italian Contaminated Sites-NPCSs), the objectives, methods and initial results of which were published by Epidemiologia & Prevenzione in 2010 and 2011. In the course of 2013, some of the SENTIERI Project findings were published in international scientific journals, and the "SENTIERI approach" was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. The present Report, set up jointly by ISS and the Italian Network of Cancer Registries (AIRTUM), as anticipated in the 2011 Report, aims to provide, for each of the 18 National Priority Contaminated Sites included in the SENTIERI Project where the Italian Association of Cancer Registries is active, a mortality update to 2010, analyses of cancer incidence (1996-2005 in 17 NPCSs) and of hospital discharges (2005-2010), as is explained in detail in Chapter 2, pertaining to the project's materials and methods. The results of the analyses for each NPCS are presented in Chapter 3, while Chapter 4 includes a critical appraisal, a discussion of the methodological approach and a series of concluding remarks. The second section of the Report takes an in-depth look at important issues of public health and scientific research in contaminated sites. This Report represents an important step towards implementing a permanent epidemiological surveillance system in Italy's contaminated sites, the ultimate goal of the SENTIERI Project.

[SENTIERI Project: materials and methods]. / Materiali e metodi del Progetto SENTIERI.

The Report considers three health outcomes - mortality, cancer incidence and hospital discharges - studied using homogenous methods and using data from official sources, namely the National Institute of Statistics (Istat), Italian Network of Cancer Registries (AIRTUM) and the Health Ministry. The timeframes of observation are: 2003-2010 for mortality, 1996-2005 for cancer incidence and 2005-2010 for hospital discharges. The causes of death are those examined by the SENTIERI Project. Hospital discharges are analysed with reference to the main diagnosis. The study of cancer incidence applies to the sites selected by AIRTUM. Statistical parameters (SMR, Standardized Mortality Ratio; SIR, Standardized Incidence Ratio; SHR, Standardized Hospitalization Ratio) were computed with a 90% confidence interval; the estimators were adjusted for age and socioeconomic status.

[SENTIERI Project: results]. / Risultati del Progetto SENTIERI.

Of the 18 National Priority Contaminated Sites (NPCSs) analysed in this Report, some have a single source of environmental contamination (such as fluoro-edenite in Biancavilla). In most cases, however, we are looking at multiple heterogeneous sources of contamination. In this respect, the a priori causal evaluation of the association between diseases and environmental exposures in NPCSs, based on epidemiological evidence, can help trace the health impact back to specific types of environmental exposure. There are several cases in which the project's findings have been consistent with a priori evidence: stomach cancer (both genders, excess cancer incidence) in the Fidenza NPCS; stomach cancer (women, excess mortality, cancer incidence and hospital discharges) in the Laguna di Grado e Marano NPCS; excess hospitalisation from respiratory diseases in Brescia-Caffaro, Milazzo and Terni Papigno NPCSs; excesses for non-Hodgkin lymphomas and melanoma (incidence and hospitalisation in men and women) and breast cancer (incidence and hospital discharges, women) in Brescia-Caffaro NPCS. In preorder to properly evaluate the population's health profile, we must also observe whether results remain consistent for all three health outcomes or in both genders. The first is the case of excess mortality, cancer incidence and hospital discharges for bladder cancer (men) in Porto Torres and diseases of the urinary tract in the Basso bacino del fiume Chienti NPCS). Gender consistency is observed, for instance, for all cancer in Bolzano, Porto Torres, Venice, Litorale Domizio Flegreo, Priolo, and Taranto, for all causes in Taranto, Litorale Domizio Flegreo and Trieste. The health impact in the various NPCSs needs to be considered carefully and used as a springboard for further analytical research that could confirm and explain causal links to specific environmental exposures. The observations can, however, already be considered as a basis for mandatory primary prevention measures.

[SENTIERI Project: discussion and conclusions]. / Discussione e conclusioni del Progetto SENTIERI.

The SENTIERI Project represents the first comprehensive analysis of the health impact of residence in National Priority Contaminated Sites (NPCSs). For the first time, it considers three distinct health outcomes: mortality (2003-2010), cancer incidence (1996- 2005) and hospital discharges (2005-2010). The Report includes a commentary explaining methodology and approach, as well as remarks on the causal association between environmental exposures and investigated health outcomes based on the a priori assessments of the epidemiological evidence; the main implications for public health and scientific research priorities are also presented. The approach put forward by SENTIERI was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. Results relating to individual diseases that can be traced back to a single agent, such as asbestiform fibres, can be easily analysed. The Biancavilla NPCS (where the fluoro-edenite asbestiform fibre was found) displays excesses of pleural mesothelioma and its proxy, malignant pleural tumours, as does Priolo, where asbestos coexists with other pollutants. Increased risk was also recorded in NPCSs adjacent to the coast hosting harbour areas (such as Trieste, Taranto and Venice) or comprising industrial areas specialising in the production of chemicals (Laguna di Grado e Marano, Priolo and Venezia) and steel (Taranto, Terni, Trieste). Increases of pathologies, such as cancer and respiratory diseases, connected to more than one agent, in industrial sites with multiple and diverse sources of exposures, prove harder to interpret. There are also more complex cases in which results do not appear consistent in the three databases or by gender (such as lung cancer in Venice, where mortality and hospital discharges have only increased among women). In order to adequately examine these we must consider factors such as the appropriateness of the health outcome showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto, where, based on the results of SENTIERI Projects and the whole available information, we can safely conclude that exposure to environmental agents played an important role, allowing us to set in place 'Integrated evaluation of environmental and health impact procedures'. SENTIERI approach does not allow definitive causal assessments. However, as stated above, these results do provide a topic for further study without getting in the way of initiatives promoting urgent environmental remediation.