Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.

Estimates of the worldwide incidence and mortality from 36 cancers and for all cancers combined for the year 2018 are now available in the GLOBOCAN 2018 database, compiled and disseminated by the International Agency for Research on Cancer (IARC). This paper reviews the sources and methods used in compiling the cancer statistics in 185 countries. The validity of the national estimates depends upon the representativeness of the source information, and to take into account possible sources of bias, uncertainty intervals are now provided for the estimated sex- and site-specific all-ages number of new cancer cases and cancer deaths. We briefly describe the key results globally and by world region. There were an estimated 18.1 million (95% UI: 17.5-18.7 million) new cases of cancer (17 million excluding non-melanoma skin cancer) and 9.6 million (95% UI: 9.3-9.8 million) deaths from cancer (9.5 million excluding non-melanoma skin cancer) worldwide in 2018.

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Insights into cancer surveillance in Central and Eastern Europe, Israel and Turkey.

The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution- and population-based registries, and present opinions on elements of an 'ideal registry' based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Breast cancer incidence trends in European women aged 20-39 years at diagnosis.

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Predictors of oropharyngeal cancer survival in Europe.

OBJECTIVES: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. MATERIALS AND METHODS: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. RESULTS: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32-0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29-0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38-4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12-11.21). CONCLUSION: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas.

BACKGROUND: Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. METHODS: Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995-1999 period for children aged 0-14 years diagnosed during 1985-1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. RESULTS: Ten-year period survival for 1995-1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. CONCLUSION: There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective.

The pioneering papers published more than one century ago by Theodor Boveri opened the way to extensive research on the mechanism linking chromosomal abnormalities to the pathogenesis of cancer. As a result of this effort, robust theoretical and empirical evidence correlating cytogenetic damage to early stages of cancer in humans was consolidated, and an increased cancer risk was postulated in healthy subjects with high levels of chromosomal aberrations (CA). The first epidemiological investigation aimed at validating CA as predictor of cancer risk was carried out in the early 1990s. In that report the Nordic Study Group described an 80% increased risk of cancer in healthy subjects with high frequencies of CA. The results of this first study were replicated a few years later in a parallel research initiative carried out in Italy, and the subsequent pooled analysis of these two cohorts published in 1998 contributed to refine the quantitative estimate of the CA/cancer association. A small case-control study nested in a cohort of subjects screened for CA in Taiwan found an increased risk in subjects with high frequency of chromosome-type CA, while in 2001 a significant increase of cancer incidence associated with high levels of CA was described in a new independent cohort of radon exposed workers from the Czech Republic. Despite some common limitations affecting study design, the studies cited above have provided results of great interest both for the understanding of mechanisms of early stages of carcinogenesis, and for their potential implication for cancer prevention. The recent evolution of molecular techniques and the refinement of high throughput techniques have the potential to improve the knowledge about the role of specific sub-types of CA and to provide further insight into the mechanisms. Finally, the most challenging perspective in the field is the passage from research to regulation, with the implementation of preventive policies based on the accumulated knowledge.

Economic evaluation of cancer registration in Europe.

BACKGROUND: Little has been reported on costs of cancer registration, and standard indicators have not yet been identified. This study investigated costs and outcomes of a sample of 18 European registries covering a population of 58.8 million inhabitants. METHODS: Through a questionnaire, we asked registries for real cost data including personnel, information technology (IT), and infrastructure. Staff costs were grouped by professional position and by activity performed. As outcomes, besides the production of current data, we considered publications in peer-reviewed journals (last 5 years' impact factor [IF]) and characteristics of registry websites. RESULTS: In our sample, the average cost of cancer registration per inhabitant was €0.27 at purchasing power standard (PPS) (range €0.03-€0.97), while the mean cost per case registered was €50.71 PPS (range €6-€213). Personnel costs accounted for an average of 79 percent of total resources. Resources spent in routine activities (an average of 51 percent, range 28 percent-87 percent) were predominant with respect to those allocated to research, with a few exceptions. Website quality seemed to be independent of total registry budget. CONCLUSIONS: The variance in costs of cancer registration across Europe can be attributed mainly to the type of registry (whether national or regional), the size of the covered population, and the national economic profile, expressed as gross domestic product.

Has there been progress in cancer care in Croatia? Assessing outcomes in a partially complete mortality follow-up setting.

BACKGROUND: We examine the possibility of assessing progress in cancer care with partially complete mortality follow-up information, and report outcomes from Croatia. METHODS: Follow-up based on death certificates indicating cancer as the cause of death was available from the Croatian National Cancer Registry. The effect of partially complete follow-up was first examined with data from the Saarland Cancer Registry by comparing absolute, relative, and cancer death certificate based survival estimates. Survival changes between 2000 and 2006 are reported for 21 common cancers amongst patients aged 15-49 and 50-59 in Croatia. RESULTS: Survival estimates based on cancer death specific follow-up could well approximate absolute and relative survival for patients aged 15-49, and relative survival for patients aged 50-59: overestimation by more than one standard error occurred 1 and 2 and 5 times, respectively, amongst 21 cancers. In Croatia, significant survival increases occurred for patients aged 15-59 with colorectal and breast cancers, patients aged 15-49 with thyroid cancer and patients aged 50-59 with malignant melanoma and prostate cancer. CONCLUSIONS: Outcome evaluation is limited with partially complete follow-up information. Internationally comparable cancer information continues to lack from South-Eastern Europe, and the provision thereof remains a highly important public health task.

Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe.

We provide updated estimates of survival, incidence, complete prevalence, and proportion cured for patients with testicular/paratesticular and extragonadal germ cell cancers in Europe, grouped according to the new list of cancer types developed by RARECARE. We collected data, archived in European cancer registries, with vital status information available to 31st December 2003. We analysed 26,000 cases of testicular, paratesticular and extragonadal germ cell cancers diagnosed 1995-2002, estimating that about 15,600 new testicular/paratesticular and 630 new extragonadal cancer cases occurred per year in EU27, with annual incidence rates of 31.5/1,000,000 and 1.27/1,000,000, respectively. Slightly more than 436,000 persons were alive at the beginning of 2008 with a diagnosis of testicular/paratesticular cancer, and about 17,000 with a diagnosis of extragonadal germ cell cancer. Five-year relative survival was 96% for testicular/paratesticular cancer and 71% for extragonadal germ cell cancer; the proportions cured were 95% and 69%, respectively. We found limited variation in survival between European regions except for non-seminomatous testicular cancer, for which five-year relative survival ranged from 86% in Eastern Europe to 96% in Northern Europe. Survival for all cancer types considered decreased with increasing age at diagnosis. Further investigation is required to establish the real reasons for the lower survival in Eastern Europe. Considering the high prevalence of these highly curable cancers, it is important to monitor patients long-term, so as to quantify treatment-related risks and develop treatments having limited impact on quality of life.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

Haematological malignancies in childhood in Croatia: investigating the theories of depleted uranium, chemical plant damage and 'population mixing'.

Some of potential causes proposed to explain the reported increase of haematological malignancies in childhood during or after the war period in several countries include depleted uranium, chemical pollution and population mixing theory. The aim of this study was to define the population of Croatian children aged 0-14 years who were potentially exposed to each of those risks during the war and to investigate any possible association between the exposure and the incidence of haematological malignancies. The authors analyzed the data reported by the Cancer Registry of Croatia during the pre-war period (1986-1990), war period (1991-1995) and post-war period (1996-1999). In the group of 10 counties potentially exposed to depleted uranium and two counties where chemical war damage occurred, no significant difference in incidence of the studied haematological malignancies was noted in comparison to pre-war period. The incidence of lymphatic leukaemia significantly increased in four counties where population mixing had occurred during the war period, supporting the 'mixing theory'. In those counties, the incidence of Hodgkin's lymphoma decreased during and after the war. In Croatia as a whole, decreases in incidence of myeloid leukaemias during war and non-Hodgkin lymphoma after the war were noted.