Lung cancer mortality in the European cohort of titanium dioxide workers: a reanalysis of the exposure-response relationship.

OBJECTIVES: Animal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers. METHODS: We reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years. RESULTS: The HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3. CONCLUSION: This analysis shows that HWSE can hide an exposure-response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure-effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.

Recent trends in incidence of five common cancers in 26 European countries since 1988: Analysis of the European Cancer Observatory.

BACKGROUND: Individual country- and cancer site-specific studies suggest that the age-adjusted incidence of many common cancers has increased in European populations over the past two decades. To quantify the extent of these trends and the recent burden of cancer, here we present a comprehensive overview of trends in population-based incidence of the five common cancers across Europe derived from a new web-based portal of the European cancer registries. METHODS: Data on incidence for cancers of the colon and rectum, prostate, breast, corpus uteri and stomach diagnosed from 1988 to 2008 were obtained from the European Cancer Observatory for cancer registries from 26 countries. Annual age-standardised incidence rates and average annual percentage changes were calculated. RESULTS: Incidence of four common cancers in eastern and central European countries (prostate, postmenopausal breast, corpus uteri and colorectum) started to approach levels in northern and western Europe, where rates were already high in the past but levelled off in some countries in recent years. Decreases in stomach cancer incidence were seen in all countries. DISCUSSION: Increasing trends in incidence of the most common cancers, except stomach cancer, are bad news to public health but can largely be explained by well-known changes in society in the past decades. Thus, current and future efforts in primary cancer prevention should not only remain focussed on the further reduction of smoking but engage in the long-term efforts to retain healthy lifestyles, especially avoiding excess weight through balanced diets and regular physical exercise.

What's next? Perspectives and future needs of cervical screening in Europe in the era of molecular testing and vaccination.

AIM: To outline the perspectives for future control of cervical cancer in Europe. METHODS: Review of current status for major cervical cancer control tools. The review was based on PubMed searches for cervical cancer prevention, Human Papillomavirus, HPV-test, HPV-vaccination, and treatment with large loop excision of the transformation zone, LLETZ. RESULTS: Recent studies suggest that condom use offers some but not complete protection against HPV-infection. High quality cytology screening with good population coverage reduces the incidence and mortality of cervical cancer. Randomised controlled trials have found HPV-testing to increase the detection rate of cervical intraepithelial neoplasia grade 2+, CIN2+, compared with cytology. Two studies found a decreased detection rate of CIN3+ in the HPV-testing arm at the subsequent screening. Randomised controlled trials found that women not infected with vaccine HPV-types at vaccination are well protected against CIN2+ from these HPV-types, but the vaccine does not protect against CIN2+ from other HPV-types and neither does it protect already HPV infected women. There is an increased risk of adverse obstetric outcomes following excisional treatment. CONCLUSIONS: The future of cervical cancer control may become a diversified strategy, one for non-vaccinated birth cohorts and another for vaccinated cohorts. It will take another 50 years before the non-vaccinated cohorts have passed the screening age. With the current uncertainty concerning the long term protection from HPV-vaccination it will furthermore be precautionary to continue screening practice for the first cohorts of HPV-vaccinated women. Organised vaccination and screening programmes with good record keeping are necessary to optimise the future control of cervical cancer.