Trends in malignant diseases in Central Serbia and factors influencing them

Abstract

Introduction: In Serbia and other countries of Central and Eastern Europe, malignant disease incidence and mortality rates have risen continuously over recent decades. Despite progress in understanding cancer epidemiology, comprehensive analyses covering all tumor localizations across both sexes using modern statistical methods remain lacking for the full 2005-2024 period. Furthermore, the impact of socioeconomic factors, healthcare availability, and events such as the COVID-19 pandemic on cancer trends has not been sufficiently investigated. Aim: To determine the time trends of incidence and mortality rates of malignant diseases in central Serbia over the period 2005-2024, identify trend breakpoints and characteristic changes, and analyze risk factors and prevention strategies for each cancer localization. Material and Method: Incidence and mortality data for malignant diseases (both sexes, 2005-2024) were obtained from the official reports of the Institute for Public Health "Dr. Milan Jovanović Batut" Belgrade. Age-standardized rates per 100,000 inhabitants were calculated separately for women and men for each cancer type, including stomach (C16), colorectal (C18-C20), liver (C22), pancreas (C25), lung and bronchus (C34), bladder (C67), brain (C71), leukemias (C91-C95), all sites (C00-C97), and all sites except skin (C44), as well as sex-specific cancers (breast, cervix uteri, corpus uteri, ovary for women; mouth/pharynx, larynx, prostate, kidney for men). Trend analysis was performed using Joinpoint Regression Program version 5.4.0, calculating Annual Percent Change (APC), Average Annual Percent Change (AAPC), 95% confidence intervals, and p-values via t-test. The permutation test was used to determine the optimal number of breakpoints (0-3), with significance set at p < 0.05. Results: Overall cancer incidence increased significantly for both sexes: AAPC = 3.20% (95% CI 0.38-6.10; p = 0.028) for women and AAPC = 6.79% (95% CI 2.37-11.41; p = 0.004) for men. Mortality also rose significantly: AAPC = 3.93% (95% CI 2.87-5.00; p < 0.001) for women and AAPC = 5.34% (95% CI 1.01-9.84; p = 0.017) for men. In common cancers for both sexes, two trend breakpoints were identified around 2017 and 2020, with a sharp increase in incidence (APC for men = 19.05% in 2017-2020) and mortality (APC for women = 14.15% in 2017-2020), followed by a post-2020 decline. Conclusion: Cancer incidence and mortality in central Serbia rose significantly from 2005 to 2024, with men showing approximately twice the rate of increase compared to women. A sharp spike in trends during 2017-2020 likely reflects a combination of improved diagnostics, changes in healthcare organization, and indirect effects of the COVID-19 pandemic including delayed diagnoses and misattribution of mortality causes. Pancreatic, liver, bladder, and kidney cancers, and leukemias represent the most dynamically increasing malignancies. Conversely, the declining trends in stomach and cervical cancers reflect clear benefits from H. pylori eradication, improved hygiene, screening programs. Regarding HPV vaccination, its long-term efficacy and potential delayed adverse effects require multi-year monitoring; thus it should be applied exclusively on a voluntary basis by adults with signed informed consent. Prevention of the rising cancers requires targeted public health interventions addressing tobacco use, obesity, diabetes, alcohol consumption, and environmental exposures.