INTRODUCTION:We estimated cancer mortality figures for 2026 in five major Asian countries and Australia, with a specific focus on prostate cancer. METHODS:We computed country- and sex-specific annual age-standardized mortality rates (ASRs) for all cancers combined and for the 10 most common cancer sites, using data from the WHO and the United Nations Population Division up to 2022 or the most recent available year. We predicted figures for 2026 and estimated the number of avoided cancer deaths in 1994-2026. RESULTS:Predicted mortality rates for all cancers combined in 2026 are favourable across all considered countries and in both sexes, with the largest declines expected in the Republic of Korea (-20.5% in males and -10.2% in females compared with 2020-2022). In 2026, the lowest predicted male rate is expected in the Philippines (72.1 per 100 000), and the highest one in Australia (92.3 per 100 000). Among females, the lowest predicted ASR (42.2 per 100 000) is in the Republic of Korea, whereas the highest one (74.1 per 100 000) in the Philippines. Trends are generally favourable for lung, stomach, colorectum, and other major neoplasms considered, except pancreas. Predicted prostate cancer mortality is favourable in all countries and across all age groups. Rates are expected to remain low in Hong Kong SAR, Japan, and the Republic of Korea, with ASRs below 4 per 100 000 males. Since the 1993 observed peak rate, an estimated 132 000 total cancer deaths were avoided in Hong Kong SAR, 75 000 in Israel, 1 366 000 in Japan, 720 000 in the Republic of Korea, 328 000 in Australia, and 102 000 among men in the Philippines. CONCLUSIONS:Declining cancer mortality is predicted in the countries considered. These trends largely reflect smoking cessation along with improvements in prevention, early detection, and treatment. However, substantial geographic disparities persist, highlighting the need for strengthened cancer control strategies, particularly in ageing populations.

We provided cancer mortality rate estimates for the year 2025 in six Latin American countries (Argentina, Brazil, Chile, Colombia, Cuba, and Mexico), focusing on prostate cancer. We extracted mortality data for all cancers combined and the most common sites from the WHO and population data since 1970 from the United Nations. Estimates for 2025 were computed applying a linear regression to the most recent segment identified through Poisson join-point regression. Avoided deaths number from 1991 to 2025 was estimated by applying the 1990 peak rate to population data. Mortality from all cancers is predicted to be favorable for both sexes in all countries. The lowest total cancer mortality rates are expected in Mexico (67.7/100 000 males; 61.4/100 000 females), while the highest ones in Cuba (136.6/100 000 males; 91.6/100 000 females). Prostate cancer mortality is declining in all countries, although rates remain high in Cuba (25.2/100 000 in 2025). Downward patterns are observed for all age groups in all countries, except the elderly in Cuba and Mexico. Declines in mortality are predicted for colorectal (except for males in Brazil and Cuba, and females in Chile), stomach (except Cuban males), pancreatic (except Argentinian and Cuban males), lung, bladder (except Argentinian females), breast, and ovarian (except Cuba) cancers. Uterine cancer mortality, particularly from cervical cancer, remains highin Argentina (10.2/100 000) and Cuba (10.4/100 000). Except for uterine, stomach, and prostate cancers, cancer mortality rates are still relatively low in Latin America, except Cuba. Controlling tobacco particularly in Cuba, implementing organized cervical cancer screening, and advancing cancer treatment also for prostate cancer remain crucial in all countries considered.

BACKGROUND:The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. METHODS:We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. RESULTS:In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥35 vs<25 kg/m2 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs<25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. CONCLUSIONS:Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

Figure S1 shows the study flowchart for the inclusion of participants. It depicts how we arrived at our final analytic population.

Characteristics of the 27 studies included in the E2C2 pooled analysis

INTRODUCTION:The relations between coffee and tea consumption and head and neck cancer (HNC) incidence are unclear. With increasing global HNC burden, this study aims to examine the association between coffee, tea, and HNC. METHODS:A pooled analysis of 9548 HNC cases and 15,783 controls from 14 individual-level case-control studies was conducted from the International Head and Neck Cancer Epidemiology consortium. Random-effects logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for HNC and its subsites, adjusting for sociodemographic and lifestyle factors. RESULTS:Compared to non-coffee drinkers, drinking >4 cups of caffeinated coffee daily was inversely associated with HNC (OR, 0.83; 95% CI, 0.69-1.00), oral cavity (OR, 0.70; 95% CI, 0.55-0.89), and oropharyngeal cancers (OR, 0.78; 95% CI, 0.61-0.99). Drinking 3-4 cups of caffeinated coffee was inversely associated with hypopharyngeal cancer (OR, 0.59; 95% CI, 0.39-0.91). Drinking decaffeinated coffee and drinking between >0 to <1 cup daily were inversely associated with oral cavity cancer (OR, 0.75; 95% CI, 0.64-0.87 and OR, 0.66; 95% CI, 0.54-0.81). Drinking tea was inversely associated with hypopharyngeal cancer (OR, 0.71; 95% CI, 0.59-0.87). Daily tea consumption of >0 to ≤1 cup was inversely associated with HNC (OR, 0.91; 95% CI, 0.84-0.98) and hypopharyngeal cancer (OR, 0.73; 95% CI, 0.59-0.91), but drinking >1 cup was associated with laryngeal cancer (OR, 1.38; 95% CI, 1.09-1.74). CONCLUSION:These findings support reduced HNC risk among coffee and tea drinkers. Future studies are needed to address geographical differences in types of coffee and tea to improve our understanding of the association of coffee and tea and global HNC risk.

Abstract Background: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. Methods: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. Results: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09–1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case–control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. Conclusions: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. Impact: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

Figure S2 is a forest plot of the association between hypertension and endometrial cancer by study site. It displays the associations between hypertension and endometrial cancer for each study site included grouped by study type (case-control, cohort)

Background Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. Materials and methods This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined ‘cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to ‘early' or ‘late' ToD of ICIs were collected from each report and pooled. Results Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. Conclusions Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

ObjectiveWe aimed at predicting cancer mortality rates for the current year for the Russian Federation, Ukraine, Israel, Hong Kong SAR, Japan, Korea, and Australia, with a focus on colorectal cancer. MethodsWe retrieved official death certification and population data from the WHO and the United Nations Population Division databases. We analyzed mortality for all cancers combined and for 10 major cancer sites from 1970 to 2019, or the latest available year. We predicted numbers of deaths and age-standardized mortality rates for 2022 using Poisson joinpoint regression models. We estimated the number of averted deaths over the period 1994-2022 because of the decline in mortality rates. ResultsTotal cancer mortality declined in all countries and both sexes. Russia had the highest total cancer predicted rates for 2022: 156.4/100 000 (world standard) in men and 81.4 in women; the lowest rates were reported in Israeli men (90.6/100 000) and Korean women (44.5/100 000). Between 1994 and 2022, a total of 1 487 000 deaths were estimated to be avoided in Russia, 502 000 in Ukraine, 58 000 in Israel, 102 000 in Hong Kong SAR, 1 020 000 in Japan, 533 000 in the Republic of Korea, and 263 000 in Australia. Colorectal cancer mortality trends were downward for the last decades with favorable predictions for 2022 in both sexes. ConclusionIn the countries considered, predicted downward trends started later and were less marked than those in the European Union and the USA. Despite overall favorable predictions, colorectal cancer remains one of the major causes of cancer mortality.

Objective The epidemiological evidence on soft-tissue sarcoma (STS) mortality is inconsistent in geographic and time coverage. This study provides mortality trends for STSs in selected countries worldwide over the last 2 decades, together with predicted figures for 2025. Methods We extracted official numbers of certified deaths coded as C47 (i.e. malignant neoplasm of peripheral nerves and autonomic nervous system) and C49 (i.e. malignant neoplasm of other connective and soft tissue) according to the 10th Revision of the International Classification of Disease and population estimates from the WHO and the Pan American Health Organization databases. We computed age-standardized (world standard population) mortality rates (ASMRs). We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2025. Results The pattern emerging from the number of deaths and ASMRs up to 2018 shows an increase in most countries in both sexes. Around 2015 to 2018, ASMRs differed by 2.5-fold in both sexes with the highest rates being registered in Central-Eastern Europe, North America and Australia, while the lowest ones in Latin America, Japan, and Korea. In 2025, the number of STS deaths is predicted to increase in most countries and both sexes, and unfavourable rates are predicted in Central Europe in both sexes. Conclusion In addition to improvements in STSs registration, unfavourable mortality rates reported in this study reflect inadequate referral of patients with STSs to high-volume multidisciplinary centres, as well as insufficient advancements in STS prevention, diagnosis, and treatments.

OBJECTIVE We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION These findings suggest the degree of industrialization and economic development affects the relationship between smoking-and alcohol with head and neck cancer.

Urinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1–2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients.

AIM:To monitor trends in childhood cancer mortality in Europe.METHODS:We calculated age-standardized mortality rates per 100,000 children (age 0-14 years) from 1990 to the last available calendar year, for all neoplasms and six main cancers in childhood, in selected European countries and geographic areas, plus the European Union (EU), using data from the World Health Organization database. We carried out a joinpoint regression analysis of mortality trends for all neoplasms, leukaemia and tumours of the nervous system. Results of the joinpoint regression were summarized through annual percent change (APC) for each identified linear segment, and weighted average APC (AAPC) over the whole period.RESULTS:From 1990 to 2015, childhood total cancer mortality rates dropped by 2.8% per year in the EU, to reach 2.6/100,000 in the latest available calendar years. The greatest declines were in central-eastern countries (AAPCs -3% to -4%). Recent rates ranged between 1.7 and 4.3 deaths/100,000, with the highest values in central-eastern Europe. Leukaemia mortality rates in the EU decreased from 1.6 to 0.6/100,000 in the latest calendar years (AAPC -4%). The deepest declines were registered in central-eastern countries, though they still showed the highest rates (0.9). The lowest leukaemia mortality rates were in northern-western Europe (0.5/100,000), but also in the Czech Republic and Poland. Southern European countries showed comparatively high rates (0.8). Nervous system tumours showed relatively modest falls (AAPC: -1.7% in the EU).CONCLUSIONS:Childhood cancer mortality continued to decline steady in Europe, though geographic differences persist. Further efforts are required to fill the gap, by promoting widespread and rational adoption of currently available treatment protocols.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Background Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

BACKGROUND:A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS:We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS:We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION:Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

BACKGROUND:To overcome the lag with which cancer statistics become available, we predicted numbers of deaths and rates from all cancers and selected cancer sites for 2019 in the European Union (EU).MATERIALS AND METHODS:We retrieved cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2014. We obtained estimates for 2019 with a linear regression on number of deaths over the most recent trend period identified by a logarithmic Poisson joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2019.RESULTS:We estimated about 1 410 000 cancer deaths in the EU for 2019, corresponding to age-standardized rates of 130.9/100 000 men (-5.9% since 2014) and 82.9 women (-3.6%). Lung cancer trends in women are predicted to increase 4.4% between 2014 and 2019, reaching a rate of 14.8. The projected rate for breast cancer was 13.4. Favourable trends for major neoplasms are predicted to continue, except for pancreatic cancer. Trends in breast cancer mortality were favourable in all six countries considered, except Poland. The falls were largest in women 50-69 (-16.4%), i.e. the age group covered by screening, but also seen at age 20-49 (-13.8%), while more modest at age 70-79 (-6.1%). As compared to the peak rate in 1988, over 5 million cancer deaths have been avoided in the EU over the 1989-2019 period. Of these, 440 000 were breast cancer deaths.CONCLUSION:Between 2014 and 2019, cancer mortality will continue to fall in both sexes. Breast cancer rates will fall steadily, with about 35% decline in rates over the last three decades. This is likely due to reduced hormone replacement therapy use, improvements in screening, early diagnosis and treatment. Due to population ageing, however, the number of breast cancer deaths is not declining.

OBJECTIVES:This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.MATERIALS AND METHODS:We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.RESULTS:For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.CONCLUSION:Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.