Prevalence and follow-up of occult HCV infection in an Italian population free of clinically detectable infectious liver disease.

BACKGROUND: Occult hepatitis C virus infection (OCI) is a recently described phenomenon characterized by undetectable levels of HCV-RNA in serum/plasma by current laboratory assays, with identifiable levels in peripheral blood mononuclear cells (PBMCs) and/or liver tissue by molecular tests with enhanced sensitivity. Previous results from our group showed an OCI prevalence of 3.3% in a population unselected for hepatic disease. The present study aimed to evaluate OCI prevalence in a larger cohort of infectious liver disease-free (ILDF) subjects. Clinical follow-up of OCI subjects was performed to investigate the natural history of the infection. METHODS AND FINDINGS: 439 subjects referred to a Turin Blood Bank for phlebotomy therapy were recruited. They included 314 ILDF subjects, 40 HCV-positive subjects and 85 HBV-positive subjects, of whom 7 were active HBV carriers. Six subjects (4/314 ILDF subjects [1.27%] and 2/7 active HBV carriers [28%]) were positive for HCV-RNA in PBMCs, but negative for serological and virological markers of HCV, indicating OCI. HCV genotypes were determined in the PBMCs of 3/6 OCI subjects two had type 1b; the other had type 2a/2c. OCI subjects were followed up for at least 2 years. After 12 months only one OCI persisted, showing a low HCV viral load (3.73×10(1) UI/ml). By the end of follow-up all OCI subjects were negative for HCV. No seroconversion, alteration of liver enzyme levels, or reduction of liver synthesis occurred during follow-up. CONCLUSIONS: This study demonstrated the existence of OCI in ILDF subjects, and suggested a high OCI prevalence among active HBV carriers. Follow-up suggested that OCI could be transient, with a trend toward the decrease of HCV viral load to levels undetectable by conventional methods after 12-18 months. Confirmation studies with a longer follow-up period are needed for identification of the OCI clearance or recurrence rates, and to characterize the viruses involved

Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents

Objectives: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. Methods: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002–2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n = 388), U.S. (CHANCE study, n = 472), and Europe (ARCAGE study, n = 502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models. Results: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58 years and median follow-up of 3.1 years (IQR = 1.4–5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR = 0.25, 95%CI = 0.18–0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p ⩽ 0.01) and after adjustment, remained significantly reduced (aHR = 0.34, 95%CI = 0.24–0.49). Among non-OP HNSCC, neither p16 (aHR = 0.83, 95%CI = 0.60–1.14), HPV16 DNA (aHR = 1.20, 95%CI = 0.89–1.63), or p16+/HPV16+ (aHR = 0.59, 95%CI = 0.32–1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction = 0.02). Conclusion: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC

Hierarchical Regression for Multiple Comparisons in a Case-Control Study of Occupational Risks for Lung Cancer

BACKGROUND Occupational studies often involve multiple comparisons and therefore suffer from false positive findings. Semi-Bayes adjustment methods have sometimes been used to address this issue. Hierarchical regression is a more general approach, including Semi-Bayes adjustment as a special case, that aims at improving the validity of standard maximum-likelihood estimates in the presence of multiple comparisons by incorporating similarities between the exposures of interest in a second-stage model. METHODOLOGY/PRINCIPAL FINDINGS We re-analysed data from an occupational case-control study of lung cancer, applying hierarchical regression. In the second-stage model, we included the exposure to three known lung carcinogens (asbestos, chromium and silica) for each occupation, under the assumption that occupations entailing similar carcinogenic exposures are associated with similar risks of lung cancer. Hierarchical regression estimates had smaller confidence intervals than maximum-likelihood estimates. The shrinkage toward the null was stronger for extreme, less stable estimates (e.g., "specialised farmers": maximum-likelihood OR: 3.44, 95%CI 0.90-13.17; hierarchical regression OR: 1.53, 95%CI 0.63-3.68). Unlike Semi-Bayes adjustment toward the global mean, hierarchical regression did not shrink all the ORs towards the null (e.g., "Metal smelting, converting and refining furnacemen": maximum-likelihood OR: 1.07, Semi-Bayes OR: 1.06, hierarchical regression OR: 1.26). CONCLUSIONS/SIGNIFICANCE Hierarchical regression could be a valuable tool in occupational studies in which disease risk is estimated for a large amount of occupations when we have information available on the key carcinogenic exposures involved in each occupation. With the constant progress in exposure assessment methods in occupational settings and the availability of Job Exposure Matrices, it should become easier to apply this approach

Effects of Italian Smoking Regulation on Rates of Hospital Admission for Acute Coronary Events: A Country-Wide Study

BACKGROUND: Several studies have reported a reduction in acute coronary events (ACEs) in the general population after the enforcement of smoking regulations, although there is uncertainty concerning the magnitude of the effect of such interventions. We conducted a country-wide evaluation of the health effects of the introduction of a smoking ban in public places, using data on hospital admissions for ACEs from the Italian population after the implementation of a national smoking regulation in January 2005. METHODS AND FINDINGS: Rates of admission for ACEs in the 20 Italian regions from January 2002 to November 2006 were analysed using mixed-effect regression models that allowed for long-term trends and seasonality. Standard methods for interrupted time-series were adopted to assess the immediate and gradual effects of the smoking ban. Effect modification by age was investigated, with the assumption that exposure to passive smoking in public places would be greater among young people. In total, 936,519 hospital admissions for ACEs occurred in the Italian population during the study period. A 4% reduction in hospital admissions for ACEs among persons aged less than 70 years was evident after the introduction of the ban (Rate Ratio [RR], 0.96; 95% Confidence Interval [CI], 0.95-0.98). No effect was found among persons aged at least 70 years (RR 1.00; 95% CI 0.99-1.02). Effect modification by age was further suggested by analyses using narrower age categories. CONCLUSIONS: Smoke-free policies can constitute a simple and inexpensive intervention for the prevention of cardiovascular diseases and thus should be included in prevention programmes

Welding and lung cancer in a pooled analysis of case-control studies.

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer

Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesINTRODUCTION: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors. METHODS: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided. RESULTS: Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk. CONCLUSIONS: For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.European Union Italian Association for Cancer Research Compagnia San Paolo Fondo Chiara Rama OLUS Swedish Childhood Cancer Foundation Norwegian Childhood Cancer Foundation La Ligue Nationale Contre le Cancer Agence Nationale pour la Recherche Scientifique Institut National du Cancer Fondation Pfizer pour la sante de l'enfant et de l'adolescent Slovenian Research Agency Swiss Paediatric Oncology Group Swiss Cancer League Swiss Cancer Research Foundation Swiss National Science Foundation Dutch Cancer Society European Unio

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer