Ethnic disparities in cancer mortality in the capital and northeast of the State of São Paulo, Brazil 2001-17.

PURPOSE: There is a paucity of studies investigating cancer disparities in groups defined by ethnicity in transitioning economies. We examined the influence of ethnicity on mortality for the leading cancer types in São Paulo, Brazil, comparing patterns in the capital and the northeast of the state. METHODS: Cancer deaths were obtained from a Brazilian public government database for the Barretos region (2003-2017) and the municipality of São Paulo (2001-2015). Age-standardized rates (ASR) per 100,000 persons-years, by cancer type and sex, for five self-declared racial classifications (white, black, eastern origin (Asian), mixed ethnicity (pardo), and indigenous Brazilians), were calculated using the world standard population. RESULTS: Black Brazilians had higher mortality rates for most common cancer types in Barretos, whereas in São Paulo, white Brazilians had higher rates of mortality from breast, colorectal, and lung cancer. In both regions, lung cancer was the leading cause of cancer death among white, black, and pardo Brazilians, with colorectal cancer deaths leading among Asian Brazilians. Black and pardo Brazilians had higher cervical cancer mortality rates than white Brazilians. CONCLUSION: There are substantial disparities in mortality from different cancers in São Paulo according to ethnicity, pointing to inequities in access to health care services.

Global variations in lung cancer incidence by histological subtype in 2020: a population-based study.

BACKGROUND: Lung cancer is the second most common cancer worldwide, yet the distribution by histological subtype remains unknown. We aimed to quantify the global, regional, and national burden of lung cancer incidence for the four main subtypes in 185 countries and territories. METHODS: In this population-based study, we used data from Cancer Incidence in Five Continents Volume XI and the African Cancer Registry Network to assess the proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma among all lung cancers by country, sex, and age group and subsequently applied these data to corresponding national (GLOBOCAN) estimates of lung cancer incidence in 2020. Unspecified morphologies were reallocated to specified subtypes. Age-standardised incidence rates were calculated using the world standard population to compare subtype risks worldwide, adjusted for differences in age composition between populations by country. FINDINGS: In 2020, there were an estimated 2 206 771 new cases of lung cancer, with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108 (39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases. Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to be 12·4, 7·7, 3·6, and 2·6 per 100 000 person-years in males and 8·3, 1·6, 1·3, and 0·9 per 100 000 person-years in females worldwide. The incidence rates of adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries in males and in all 185 countries in females. The highest age-standardised incidence rates per 100 000 person-years for adenocarcinoma, squamous cell carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for males occurred in eastern Asia (23·5), central and eastern Europe (17·5), western Asia (7·2), and south-eastern Asia (11·0); and for females occurred in eastern Asia (16·0), northern America (5·4), northern America (4·7), and south-eastern Asia (3·4). The incidence of each subtype showed a clear gradient according to the Human Development Index for male and female individuals, with increased rates in high and very high Human Development Index countries. INTERPRETATION: Adenocarcinoma has become the most common subtype of lung cancer globally in 2020, with incidence rates in males exceeding those of squamous cell carcinoma in most countries, and in females in all countries. Our findings provide new insights into the nature of the global lung cancer burden and facilitates tailored national preventive actions within each world region. FUNDING: None.

The Economic Cost of Thyroid Cancer in France and the Corresponding Share Associated With Treatment of Overdiagnosed Cases.

OBJECTIVES: Thyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases. METHODS: Multiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21 departments using data from the French network of cancer registries and extrapolated to the whole country; medical records from 6 departments were used to refine the diagnosis and care pathway. RESULTS: Between 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer, with mean cost per capita of €6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to overdiagnosis. The total cost of thyroid cancer patient management was €203.5 million (€154.3 million for women and €49.3 million for men), of which between €59.9 million (or 29.4% of the total cost, lower bound) and €115.9 million (or 56.9% of the total cost, upper bound) attributable to treatment of overdiagnosed cases. CONCLUSIONS: The management of thyroid cancer represents not only a relevant clinical and public health problem in France but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important role on the total costs of thyroid cancer management.

Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: Using a toolkit approach, Tsuda et al. critiqued work carried out by or in collaboration with the International Agency for Research on Cancer (IARC/WHO), including the IARC technical publication No. 46 on "Thyroid health monitoring after nuclear accidents" (TM-NUC), the project on nuclear emergency situations and improvement on medical and health surveillance (SHAMISEN), and the IARC-led work on global thyroid cancer incidence patterns as per IARC core mandate. MAIN BODY: We respond on the criticism of the recommendations of the IARC technical publication No. 46, and of global thyroid cancer incidence evaluation. CONCLUSION: After nuclear accidents, overdiagnosis can still happen and must be included in informed decision making when providing a system of optimal help for cases of radiation-induced thyroid cancer, to minimize harm to people by helping them avoid diagnostics and treatment they may not need.

Thyroid Cancer Incidence and Mortality by Socioeconomic Level in the State of São Paulo, Brazil 2001-2017.

OBJECTIVE: Thyroid cancer is rising largely due to greater detection of indolent or slow-growing tumors; we sought to compare the incidence and mortality profiles of thyroid cancer in the State of São Paulo by socioeconomic status (SES). METHODS: Data on thyroid cancer cases diagnosed from 2003 to 2017 in the Barretos Region and from 2001 to 2015 in the municipality of São Paulo were obtained from the respective cancer registries. Corresponding death data were obtained from a Brazilian public government database. Age-standardized rates were calculated and presented as thematic maps. The rates were also calculated by SES and spatial autocorrelation was assessed by global and local indices. RESULTS: There were 419 cases of thyroid cancer and 21 deaths in Barretos, contrasting with the highly populated São Paulo, with 30 489 cases and 673 deaths. The overall incidence rates in São Paulo (15.9) were three times higher than in Barretos (5.7), while incidence rates in women were close to five times higher in Barretos and four times higher in São Paulo than in men. Mortality rates were, in relative terms, very low in both regions. A clear stepwise gradient of increasing thyroid cancer incidence with increasing SES was observed in São Paulo, with rates in very high SES districts four times those of low SES (31.6 vs 8.1). In contrast, the incidence rates in Barretos presented little variation across SES levels. CONCLUSION: Thyroid cancer incidence varied markedly by SES in São Paulo, with incidence rates rising with increasing socioeconomic index. Overdiagnosis is likely to account for a large proportion of the thyroid cancer burden in the capital.

Global patterns of Hodgkin lymphoma incidence and mortality in 2020 and a prediction of the future burden in 2040.

Our study examines global patterns of Hodgkin lymphoma (HL) in 2020 and predicts the future incidence and mortality burden in 2040 using IARC's GLOBOCAN estimates of the number of new cases and deaths of HL in 185 countries. A total of 83 000 new cases of HL and 23 000 deaths from HL were estimated in 2020. In general, incidence and mortality rates were consistently higher in males (50% more cases and deaths than females) across world regions and countries. Incidence rates varied markedly by world region, at least 10-fold in both sexes, with the highest incidence rates observed in Southern Europe. Mortality exhibited an inverse pattern compared to incidence, with rates elevated in Western Asia and Northern Africa. The number of HL incident cases is predicted to rise to around 107 000 cases (a 30% increase) by 2040 due to demographic changes, assuming global rates in 2020 remains unchanged. The findings provide a baseline and impetus for developing strategies that aim to reduce the burden of HL in future decades.

The influence of postscreening follow-up time and participant characteristics on estimates of overdiagnosis from lung cancer screening trials.

We aimed to explore the underlying reasons that estimates of overdiagnosis vary across and within low-dose computed tomography (LDCT) lung cancer screening trials. We conducted a systematic review to identify estimates of overdiagnosis from randomised controlled trials of LDCT screening. We then analysed the association of Ps (the excess incidence of lung cancer as a proportion of screen-detected cases) with postscreening follow-up time using a linear random effects meta-regression model. Separately, we analysed annual Ps estimates from the US National Lung Screening Trial (NLST) and German Lung Cancer Screening Intervention Trial (LUSI) using exponential decay models with asymptotes. We conducted stratified analyses to investigate participant characteristics associated with Ps using the extended follow-up data from NLST. Among 12 overdiagnosis estimates from 8 trials, the postscreening follow-up ranged from 3.8 to 9.3 years, and Ps ranged from -27.0% (ITALUNG, 8.3 years follow-up) to 67.2% (DLCST, 5.0 years follow-up). Across trials, 39.1% of the variation in Ps was explained by postscreening follow-up time. The annual changes in Ps were -3.5% and -3.9% in the NLST and LUSI trials, respectively. Ps was predicted to plateau at 2.2% for NLST and 9.2% for LUSI with hypothetical infinite follow-up. In NLST, Ps increased with age from -14.9% (55-59 years) to 21.7% (70-74 years), and time trends in Ps varied by histological type. The findings suggest that differences in postscreening follow-up time partially explain variation in overdiagnosis estimates across lung cancer screening trials. Estimates of overdiagnosis should be interpreted in the context of postscreening follow-up and population characteristics.

Are U.S. trends a barometer of future cancer transitions in emerging economies?

The currently high cancer incidence rates in the U.S. and other high-income countries have been strongly affected by the acquisition of environmental and lifestyle risk factors that accompanied socioeconomic growth in the second half of the last century. The very same factors are now operating in many low- and middle-income countries (LMIC) undergoing rapid socioeconomic transition. A parallel is drawn between the past cancer trends in the U.S. and those anticipated in LMIC transitioning towards higher levels of socioeconomic development. We expect to see a major upsurge in the (still low to intermediate) cancer incidence and mortality rates in LMIC over the next decades, which coupled with population aging and growth, would translate to a scale of individuals diagnosed with, living and dying from cancer unparalleled in history. On account of resource constraints and organizational limitations, prevention strategies need to be prioritized in LMIC.

Profiling global cancer incidence and mortality by socioeconomic development.

Economic and living conditions have improved over time in most countries, although often in association with detrimental lifestyle and environmental changes that are major determinants of cancer. In this ecological study, we assess the association between national socioeconomic levels and incidence and mortality rates for all cancers combined and 27 cancer types, in 175 countries. We obtained national level cancer incidence and mortality estimates for 2018 from GLOBOCAN and computed an index of socioeconomic development based on national education and income levels extracted from the United Nations Development Programme. Cancer incidence rates are strongly positively associated with the national socioeconomic level for all cancers combined and for a large number of cancer types, in both sexes. Conversely, the association between socioeconomic development and cancer mortality rates is less clear. The most common pattern for type-specific cancers is an increasing incidence rate with a relatively stable mortality rate as socioeconomic development increases. Despite the high incidence rates for many cancer types, mortality rates are relatively low in high-income countries, partly due to the availability of early detection and effective treatments. As socioeconomic development continues to rise, countries with currently low- and medium-development levels may experience large increases in the incidence of several cancers. Given the limited resources and lack of infrastructure, increases in incidence rates in low-income countries will likely be paralleled by increases in mortality rates. Efforts to plan, implement and evaluate prevention programs must therefore be considered as greater priorities in Low- and Middle-income countries.

Time trends and other sources of variation in Helicobacter pylori infection in mainland China: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H pylori) is a carcinogen that causes a huge burden of gastric cancer in China. We aimed to evaluate the temporal trends and other sources of variation of H pylori infection in adults from mainland China. MATERIALS AND METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases for articles published from January 1983 to June 2020. We included studies reporting H pylori prevalence in adults and then applied random effect meta-analyses to obtain pooled prevalence estimates for all studies and subgroups. Sources of heterogeneity were investigated by moderator analysis, and time trends were assessed through random effect meta-regression. RESULTS: Of the 2121 studies identified, 98 were eligible for inclusion. The pooled estimate of 670 572 participants from 26 provinces during 1983-2018 was 49.6% (95% CI: 46.9%, 52.4%). H pylori prevalence varied considerably, ranging from 20.6% to 81.8%. Periods, urban/rural status, detection method, and study design explained 18.8%, 24.0%, 17.8%, and 30.4% of the heterogeneity, respectively. Overall, H pylori prevalence declined by -0.9% (95% CI: -1.1%, -0.6%) annually. Consistent declines in prevalence were observed by sex, age, and study characteristics. CONCLUSIONS: Helicobacter pylori prevalence is slowly decreasing over time in mainland China, but the low declining speed is not enough to have a major impact on gastric cancer incidence for many years. The time trends and the large heterogeneity should be taken into account when conducting regional comparisons, disease burden estimations, and customized strategy making.

Hepatitis B Virus Blocks the CRE/CREB Complex and Prevents TLR9 Transcription and Function in Human B Cells.

Effective B cell responses such as cytokine secretion, proliferation, and Ab-specific responses are essential to clear hepatitis B virus (HBV) infection. However, HBV alters numerous immune pathways to persist in the host. B cell activity depends on activation of the innate sensor TLR9 by viral or bacterial DNA motifs. How HBV can deregulate B cell functions remains unknown. In this study, we show that HBV can enter and decrease TLR9 expression in human primary B cells. Using PBMCs from human blood donors, we show that TLR9 expression was reduced in all peripheral B cells subsets exposed to HBV. B cell function mediated by TLR9, but not TLR7, such as proliferation and proinflammatory cytokines secretion, were abrogated in the presence of HBV; however, global Ig secretion was not downregulated. Mechanistically, we show, using human myeloma B cell line RPMI 8226, that the surface Ag hepatitis B surface Ag was responsible for TLR9 dysfunction. hepatitis B surface Ag suppressed the phosphorylation and thus the activation of the transcription factor CREB, preventing TLR9 promoter activity. Finally, we corroborated our in vitro findings in a cohort of chronic HBV carriers and found that TLR9 expression and function were significantly suppressed. The effect of HBV on TLR9 activity in B cells gives insights into oncoviral immune escape strategies, providing knowledge to develop novel immunotherapeutic approaches in chronic HBV-carrier patients.

Thyroid cancer "epidemic" also occurs in low- and middle-income countries.

Thyroid cancer incidence varies greatly between and within high-income countries (HICs), and overdiagnosis likely plays a major role in these differences. Yet, little is known about the situation in low- and middle-income countries (LMICs). We compare up-to-date thyroid cancer incidence and mortality at national and subnational levels. 599,851 thyroid cancer cases in subjects aged 20-74 reported in Cancer Incidence in Five Continents volume XI from 55 countries with at least 0.5 million population, aged 20-74 years, covered by population-based cancer registration, and 22,179 deaths from the WHO Mortality Database for 36 of the selected countries, over 2008-2012, were included. Age-standardized rates were computed. National incidence rates varied 50-fold. Rates were 4 times higher among women than men, with similar patterns between countries. The highest rates (>25 cases per 100,000 women) were observed in the Republic of Korea, Israel, Canada, the United States, Italy, France, and LMICs such as Turkey, Costa Rica, Brazil, and Ecuador. Incidence rates were low (<8) in a few HICs (the Netherlands, the United Kingdom, and Denmark) and lowest (3-4) in some LMICs (such as Uganda and India). Within-country incidence rates varied up to 45-fold, with the largest differences recorded between rural and urban areas in Canada (HIC) and Brazil, India, and China (LMICs). National mortality rates were very low (<2) in all countries and in both sexes, and highest in LMICs. The very high thyroid cancer incidence and low mortality rates in some LMICs also strongly suggest a major role of overdiagnosis in these countries.

Assessing global transitions in human development and colorectal cancer incidence.

Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30-74 years) age-standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level.

Preventable fractions of cervical cancer via effective screening in six Baltic, central, and eastern European countries 2017-40: a population-based study.

BACKGROUND: Cervical cancer incidence remains high in several Baltic, central, and eastern European (BCEE) countries, mainly as a result of a historical absence of effective screening programmes. As a catalyst for action, we aimed to estimate the number of women who could be spared from cervical cancer across six countries in the region during the next 25 years, if effective screening interventions were introduced. METHODS: In this population-based study, we applied age-period-cohort models with spline functions within a Bayesian framework to incidence data from six BCEE countries (Estonia, Latvia, Lithuania, Belarus, Bulgaria, and Russia) to develop projections of the future number of new cases of cervical cancer from 2017 to 2040 based on two future scenarios: continued absence of screening (scenario A) versus the introduction of effective screening from 2017 onwards (scenario B). The timespan of available data varied from 16 years in Bulgaria to 40 years in Estonia. Projected rates up to 2040 were obtained in scenario A by extrapolating cohort-specific trends, a marker of changing risk of human papillomavirus (HPV) infection, assuming a continued absence of effective screening in future years. Scenario B added the effect of gradual introduction of screening in each country, under the assumption period effects would be equivalent to the decreasing trend by calendar year seen in Denmark (our comparator country) since the progressive regional introduction of screening from the late 1960s. FINDINGS: According to scenario A, projected incidence rates will continue to increase substantially in many BCEE countries. Very high age-standardised rates of cervical cancer are predicted in Lithuania, Latvia, Belarus, and Estonia (up to 88 cases per 100 000). According to scenario B, the beneficial effects of effective screening will increase progressively over time, leading to a 50-60% reduction of the projected incidence rates by around 2040, resulting in the prevention of cervical cancer in 1500 women in Estonia and more than 150 000 women in Russia. The immediate launch of effective screening programmes could prevent almost 180 000 new cervical cancer diagnoses in a 25-year period in the six BCEE countries studied. INTERPRETATION: Based on our findings, there is a clear need to begin cervical screening in these six countries as soon as possible to reduce the high and increasing incidence of cervical cancer over the next decades. FUNDING: None.

Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR.

GP5+/6+-based PCR followed by reverse line blot hybridization (GP5+/6+RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5+/6+RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5+/6+RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5+/6+RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5+/6+RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5+/6+RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5+/6+RLB than for those negative for the same type by GP5+/6+RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5+/6+RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5+/6+RLB, suggesting the existence of masking effects due to competition for GP5+/6+ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination.