Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

A Retrospective Cohort Study of Young Women Spontaneously Choosing to Be Vaccinated against HPV: Outcomes from Their First Cervical Cancer Screening Test.

BACKGROUND: Efficacy for cervical cancer prevention of opportunistic HPV vaccination in post-pubertal girls is lower than in 11-year-olds. METHODS: Women born between 1986 and 1992 vaccinated at 15-25 years of age (at least one dose of 4-valent HPV vaccine) and screened at 24-27 years of age were included. Frequency of opportunistic vaccination, overall and by birth cohort, was calculated; screening outcomes were compared between vaccinated and unvaccinated women. RESULTS: Overall, 4718 (4.9%) HPV-vaccinated, and 91,512 unvaccinated, women were studied. The frequency of vaccination increased by birth cohort, ranging between 1.8% and 9.8%; age at vaccination decreased progressively by birth cohort (p < 0.0001). Participation in screening was 60.8% among vaccinated, and 56.6% among unvaccinated, women (p < 0.0001). Detection rates (DR) for high-grade lesions were lower in vaccinated women (2.11‰ vs. 3.85‰ in unvaccinated, for CIN3+, p = 0.24; 0.0‰ vs. 0.22‰ for cancer). The DR of CIN3+ increased with age at vaccination, scoring respectively 0.0‰, 0.83‰, and 4.68‰ for women vaccinated when they were 15-16, 17-20, and 21-25 years old (p = 0.17). CONCLUSIONS: In comparison to unvaccinated women, higher compliance with cervical cancer screening invitation and lower CIN3+ DR among vaccinated women was observed. Age at vaccination was inversely correlated to vaccination efficacy.

Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure.

OBJECTIVE: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers. METHODS: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis. METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time. RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer. CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.

Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom.

OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom. METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers. RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL). CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers. IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.

Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.

OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers. METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.

[Increased risk of mesothelioma and lung cancer among workers exposed to asbestos who could require an anticipated retirement]. / Elevato rischio di mesotelioma pleurico e tumore del polmone tra i lavoratori esposti ad amianto titolati a richiedere un pensionamento anticipato.

OBJECTIVES: to assess the association among malignant pleural mesothelioma (MPM) and lung cancer (LC) among workers who have been exposed to asbestos and have or not have required an anticipated leave from work, a possibility offered by the 1992 law banning asbestos in Italy, in the framework of the health surveillance programmes on going in the Veneto Region (Northern Italy). SETTING AND PARTICIPANTS: a cohort of asbestos workers derived from the rosters of selected factories and alive in 1992, followed from 1992 to 2012.MPM cases have been identified through the Regional Mesothelioma Registry, while LC cases through a link with the Regional Cancer Registry, hospital discharges, and death certificates. Risks related to asbestos exposure were calculated by mixed effects Poisson regression model. RESULTS: the risk of MPM and LC increases at any additional duration of work, up to very high values for long term durations of work for MPM, and up to a three fold increase for LC. Early retirements have been requested by a fraction only in the position of submitting it. CONCLUSION: subjects who have been exposed to asbestos should be the target of a post-occupational surveillance, and further work is suggested to identify subjects at high risk of LC because of smoking habits and more heavy exposure to asbestos, in order to develop programmes for primary and secondary cancer prevention.

[Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy]. / Valutazione della variazione temporale del rischio di mesotelioma e di tumore del polmone nelle coorti di esposti ad amianto per lavoro in Italia.

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

[Confirmation of an excess of cancer mortality in a cohort of workers of a chromium thin-layer plating]. / Conferma di un eccesso di mortalità per tumori in una coorte di addetti a cromatura a strato sottile.

OBJECTIVES: to extend up to year 2013 the follow-up for mortality of a cohort of workers in a chromium and nickel plating plant, where an excess of lung cancers was already identified. DESIGN: 10 years after the first study about cancer mortality in a cohort of workers involved in the chromium thin-layer plating, published in 2006, we updated the evaluation of themortality of a cohort ofworkers employed in the same chromiumthin-layer plating factory with at least 6 months of work between 1968 and 1994.The mortality rates are compared with those of the Italian and Veneto Region (Northern Italy) populations.The dose-response relationship between work duration and lung cancer is assessed by adjusted Poisson regression. SETTING AND PARTICIPANTS: 127 unskilled or skilled workers involved in the production process. RESULTS: in the updated follow-up, 35 deaths occurred among the subjects under study: 19 for cancer (of which 11 for lung cancer and 3 for pancreatic cancer). A marked excess ofmortality due to lung cancer is observed. In addition, the newfollowup shows a significant excess of pancreatic cancer mortality. Lung cancer mortality is positively associated with work duration and the risk increases by 13%(95%CI 1-26) for each additional year of work. CONCLUSIONS: the extension of followup confirms that this cohort expresses an increased mortality from cancer deaths, due to a marked excess of lung and pancreatic cancers. The effect of smoking has only a secondary effect in the cancer onset expressed by this cohort. The risk of lung cancer increased with work duration and thus with occupational exposure to chromium and nickel.

Past trends and future prediction of mesothelioma incidence in an industrialized area of Italy, the Veneto Region.

BACKGROUND: Malignant Mesothelioma (MM) is so associated with (professional, familial or environmental) asbestos exposure that trends in incidence and mortality parallel, after 30-40 years, the trend in asbestos consumption. In recent decades, the industrialized countries have witnessed a steady growth of pleural MM (MPM), following a stabilization or decline in rates in the countries that first adopted restrictive policies. The aim of this study was to evaluate the temporal variations of pleural MM incidence in the Veneto Region of Italy in the period 1987-2010. METHODS: We included only MPM with histological or cytological diagnosis. Age-Period-Cohort (APC) models were used to assess the trend in the incidence of MPM in both genders. Future predictions were evaluated by using a Bayesian APC model. RESULTS: In the period 1987-2010, 1600 MPMs have occurred. We observe a positive trend in the incidence in the whole period considered. The APC model showed that in both genders the cohort at higher risk is the one born between the years 1940-1945. Future projections indicate that the trend will decrease after the incidence peak of 2010; yet 1234 men are expected to develop a mesothelioma between 2011 and 2026. Among women, the future MPM rates will be stable or slightly decreasing. CONCLUSIONS: The asbestos ban introduced in Italy in the year 1992 as a prospective result will certainly determine a decreasing incidence. However, the extremely long latency of MPM means that its influence is not yet observable.

[The effectiveness of compensation system for mesotheliomas due to occupational exposure to asbestos and determinants for requests and awards: an evaluation based on record-linkage between the Veneto Mesothelioma Register and the claims and compensations recorded by the National Insurance Institute (INAIL)]. / I fattori che influenzano in Italia la domanda e il riconoscimento dei mesoteliomi di origine professionale: analisi basata su record-linkage tra dati del registro regionale del Veneto e INAIL.

AIM: To determine the rate of requests for compensation and of compensations awarded for mesothelioma cases due to occupational exposure to asbestos; to identify factors that may influence the outcome; to provide an appreciation of the amount of compensation. DESIGN AND MAIN OUTCOME MEASURES: Record-linkage study at individual level between the new cases of mesothelioma occurred among the residents of the Veneto Region (Northern Italy) between 1999- 2007 and the file of the Insurance Institute, with individual data on all claims and compensations. Adjusted logistic regression models were used to estimated the association between submitting claims and obtaining an award and socio-demographic and other characteristics. RESULTS: 349 on 499 mesotheliomas considered to be due to occupational exposure to asbestos submitted a claim (70% of those of occupational origin) and 72%of claims were accepted. The welfare system covers only 35%of mesothelioma occurred. The probability of submitting and obtaining a claim was associated with gender, cancer site, age at diagnosis, vital status, and residence or local office in charge of the evaluation. A strong discrimination against women is observed. If exposure to asbestos at work was due to a direct manipulation of asbestos, claims were more easily accepted.As a consequence,mesothelioma occurred among construction workers, the occupational activity at the origin of the largest number of occurring mesotheliomas, are more frequently rejected.When submitted by a relative, the lag between a request for compensation and the decision is on average of about two years. CONCLUSION: This is the first study in Italy using a record-linkage method and was made possible thanks to a population based mesothelioma Register and the availability of memorized information of the Insurance Institute.The welfare system shown clear limitations and there is the need for more appropriate strategies.

[Mesothelioma in construction workers: risk estimate, lung content of asbestos fibres, claims for compensation for occupational disease in the Veneto Region mesothelioma register]. / Mesoteliomi negli edili: frequenza, stima del rischio, carico polmonare di fibre di amianto, domande e riconoscimenti per malattia professionale nel Registro regionale veneto dei casi di mesotelioma.

BACKGROUND: Work in the construction industry is causing the highest number of mesotheliomas among the residents of the Veneto Region (north-east Italy, 4,5 million inhabitants). OBJECTIVES: To sum up the results on occurrence, asbestos exposure, lung fibre content analyses, and compensation for occupational disease. METHODS: Case identification and asbestos exposure classification: active search of mesotheliomas that were diagnosed via histological or cytological examinations occurring between 1987 and 2006; a probability of asbestos exposure was attributed to each case, following interviews with the subjects or their relatives and collection of data on the jobs held over their lifetime. Risk estimate among construction workers: the ratio between cases and person-years, the latter derived from the number of construction workers reported by censuses. Lung content of asbestos fibres: examination of lung specimens by Scanning Electron Microscope to determine number and type of fibres. Claims for compensation and compensation awarded: data obtained from the National Institute for Insurance against Occupational Diseases available for the period 1999-2006. RESULTS: of 952 mesothelioma cases classified as due to asbestos exposure, 251 were assigned to work in the construction industry (21 of which due to domestic of environmental exposures), which gives a rate of 4.1 (95% CI 3.6-4.8) x 10(5) x year among construction workers. The asbestos fibre content detected in the lungs of 11 construction workers showed a mean of 1.7 x 10(6) fibres/g dry tissue (range 350,000-3 million) for fibres > 1 micro, almost exclusively due to amphibole fibres. 62% of the claims for compensation were granted but the percentage fell to less than 40% when claims were submitted by a relative, after the death of the subject. CONCLUSION: The prevalence of mesothelioma occurring among construction workers is high and is associated with asbestos exposure; the risk is underestimated by the subjects and their relatives. All mesotheliomas occurring among construction workers should be granted compensation for occupational disease.

[Malignant mesothelioma in the Veneto Region (north-east of Italy), 1988-2002: incidence, geographical analysis, trends and comparison with mortality]. / L'incidenza del mesotelioma maligno in Regione Veneto nel periodo 1988-2002: analisi geografica, trend e confronto con la mortalità.

OBJECTIVE: The study assesses incidence and trend of malignant mesothelioma (MM), and mortality from primary pleural tumour (PPT) among residents of the Veneto region (North-east of Italy 4,450,000 inhabitants at the last census). The study also aims at identifying areas at high risk, by applying geographical analysis techniques. METHOD: The results have been obtained through the activity ofa Mesothelioma Registry, established in 2001, thus collecting largely retrospective data. Incidence and trends are estimated on MM diagnosed between 1988 and 2002 by means of histological or cytological techniques. Deaths from PPT are derived through the availability of mortality records for the period 1988-1999 (latest year available). Direct age-standardization was applied to provincial rates (7 provinces), whereas standardized mortality and incidence ratios according to Kernel estimates and spatial scan statistics have been used to identify clusters at the municipality level (581 municipalities). RESULTS AND CONCLUSIONS: the incidence of MM in the Veneto region appears similar to that of other northern Italian regions (904 new MM cases from 1988 to 2002, 650 among males, 819 pleural; age-standardized annual incidence rates x 100,000 in the period 1988-1999): 1.75 (IC 95% 1.59-1.91) among males, based on 460 cases, and 0.67 (IC 95% 0.57-0.77) among females, based on 196 cases, and displays an increasing trend among both genders. Among males incidence doubles during the study period. High risks are detected among males in a cluster formed by the city of Venice and surrounding municipalities (Standardized Incidence Ratio, SIR, for pleural mesothelioma, 1988-1999, 2.94 (p = 0.001) for the cluster based on 110 observed cases), and, in addition to Venice, in the province of Padua among females (SIR from pleural mesothelioma, 1988-1999, 1.98 (p = 0.001) for the cluster based on 95 observed cases). Mortality from TPP turns out to be higher than incidence and tends to approach incidence in more recent years; this may be explained by the increasing application of diagnostic procedures, inclusive of histopathological tests, among old patients.