Ovarian cancer was the eighth most frequently diagnosed cancer among women in 2022. The global age-standardized incidence rate of ovarian cancer decreased from 7.22/100,000 to 6.71/100,000 from 1990 to 2021. However, incidence trends varied across countries. Declining ovarian cancer incidence rates were reported in high-income countries, such as the United States, Austria, the Netherlands, and Norway, while there were increasing incidence rates in Africa and parts of Asia, including Japan and India. The global age-standardized mortality rate of ovarian cancer decreased from 4.73/100,000 to 4.06/100,000 between 1999 and 2021 with varying trends among countries. Moreover, the age-standardized 5-year net ovarian cancer survival rate in most countries remained < 50%. Several specific factors related to ovarian cancer risk have been identified, including reproductive factors, use of oral contraceptives, anti-inflammatory diets, endometriosis, pelvic inflammatory disease, obesity, diabetes, and occupational asbestos exposure. No screening or prevention strategy has been proven effective in downstaging or reducing mortality from ovarian cancer in an average-risk population without a family cancer history or pathogenic variants. Indeed, risk-reducing salpingo-oophorectomy remains the gold standard for lowering the risk of ovarian cancer in high-risk individuals with hereditary mutations. This review provides a comprehensive overview of the epidemiology, risk factors, screening, and prevention of ovarian cancer, aiming to offer a global perspective on public health strategies for addressing the disease.
OBJECTIVE:Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. This study was aimed at estimating regional and national variations in lifetime CRC risk worldwide. METHODS:CRC data were extracted from GLOBOCAN 2022, including 185 countries, and population and all-cause mortality data were sourced from the United Nations. The world was divided into 20 geographical regions and categorized by Human Development Index (HDI). Lifetime CRC risk was estimated with the life table method, adjusted for multiple primary cancers. RESULTS:In 2022, the lifetime risks of developing and dying from CRC were 2.69% [95% confidence interval (CI): 2.68-2.70] and 1.39% (95% CI: 1.39-1.40), respectively. Men had a higher risk of colon cancer than rectal cancer, and higher CRC risk than women. Lifetime risk varied by region and HDI: regions with very high, high, moderate, and low HDI had incidence risks of 5.17%, 2.75%, 0.72%, and 0.57%, respectively, and mortality risks of 2.48%, 1.50%, 0.44%, and 0.41%, respectively. Australia/New Zealand had the highest incidence risk (7.41%, 95% CI: 7.30-7.52), and Northern Europe the highest mortality risk (3.28%, 95% CI: 3.24-3.32). Risks were stable before 40 years of age, peaked in middle age, and declined after 70 years of age. Temporally, Thailand had the highest increasing trend in lifetime risk, whereas the United States and Austria showed a decreasing trend. CONCLUSIONS:Lifetime CRC risk differs by subtype, sex, HDI, and geography, and residual risk gradually decreases with age. Targeted primary prevention strategies should be implemented in various countries and regions to mitigate CRC burden.
Human papillomavirus(HPV)is the most prevalent sexually transmitted infection worldwide1.More than 200 HPV geno-types have been identified and are classified as high-risk HPV(HR-HPV)or low-risk HPV(LR-HPV)according to their onco-genic potential.
Objective: Bone metastases are refractory to current therapies, primarily owing to the immunosuppressive metastasis tumor microenvironment (TME), which is dominated by myeloid cells. However, the function and regulatory mechanisms of myeloid compartments within the bone TME are incompletely understood. Herein we sought to delineate the role of the DKK1-CKAP4 axis in shaping myeloid cell-mediated immunosuppression in bone metastases and to identify potential therapeutic strategies targeting this pathway. Methods: The composition and phenotypic characteristics of myeloid cells in the bone TME were analyzed. Mechanistic studies were conducted using ex vivo co-culture systems and an in vivo Ckap4fl/flS100a8Cre (neutrophil-specific Ckap4 knockout) mouse model to delineate the role of the DKK1-CKAP4 axis in regulating neutrophil maturation, osteoclast-like cell differentiation, and macrophage polarization. The therapeutic efficacy of DKK1 blockade in combination with zoledronic acid, as well as the impact on remodeling the TME, was further validated in bone metastasis mouse models. Results: Significant expansion and predominance of myeloid cells within the bone TME was noted. Mechanistically, the DKK1-CKAP4 axis regulated the development and function of multiple myeloid populations. The DKK1-CKAP4 axis drove neutrophils toward an immature-like, immunosuppressive phenotype, promoted osteoclast-like cell differentiation, and induced macrophage polarization into an M2-like phenotype. Importantly, combined therapy with DKK1 blockade and zoledronic acid reprogrammed immunosuppressive myeloid cells, restored antitumor immunity, and significantly reduced tumor burden in bone metastasis models. Conclusions: The findings herein showed the DKK1-CKAP4 axis to be a key regulator of myeloid-driven immunosuppression in the bone TME. The combination of DKK1 blockade with zoledronic acid represents a potential therapeutic strategy for bone metastases.
OBJECTIVE:Breast cancer is the most frequently diagnosed cancer among women worldwide and is a leading cause of cancer-related deaths. Comparative assessments of breast cancer lifetime risks across populations are limited. This study estimated the global, regional, and national lifetime risks, temporal trends, and socioeconomic inequalities in the burden of breast cancer. METHODS:Using incidence and mortality data from GLOBOCAN 2022 (185 countries) and United Nations population and all-cause death data, lifetime risks were calculated using the adjusted for multiple primaries (AMP) method, which could adjust for multiple primary cancers, competing risks of other causes death, and life expectancy. Longitudinal data of breast cancer incidence from 2003-2017 were retrieved from the Cancer Incidence in Five Continents (CI5) Plus database. The temporal trends for breast cancer deaths were abstracted from the WHO Mortality Database. The lifetime risk of developing and dying from breast cancer were analyzed by socioeconomic characteristics, 20 predefined geographic regions and menopausal status. RESULTS:The overall worldwide lifetime risk of developing and dying from breast cancer was 5.51% (95% CI: 5.50%-5.52%) and 1.82% (95% CI: 1.82%-1.83%) in 2022, respectively. The estimated lifetime risks of developing breast cancer had a positive relationship with Human Development Index (HDI) levels and corresponding risks of 10.37%, 4.42%, 2.96%, and 2.91% in very high, high, middle, and low HDI regions, respectively. Very high HDI regions presented the highest lifetime risk of breast cancer death (2.70%), followed by low HDI (1.70%), medium HDI (1.54%), and high (1.38%) HDI regions. A significant correlation was identified between lifetime risks and health economics capacity. The lifetime risk of developing and dying from breast cancer primarily involved individuals ≥ 55 years of age with remaining risks of 3.77% (developing) and 1.43% (dying) from 55 years to death. The proportion of lifetime risks among individuals 0-44 years of age was higher in Africa regions compared to other regions. In surveillance data from 36 countries, a significant increasing trend in the average annual percentage change (AAPC) was noted in 32 countries, which ranged from 0.17% in the United States to 5.84% in the Republic of Korea. CONCLUSIONS:Globally, an estimated 1 in 18 individuals were diagnosed with breast cancer during their lifetime and approximately 1 in 55 died from the disease in 2022. Lifetime risk of breast cancer disparities reveal the socioeconomic inequalities of breast cancer. Therefore, country-tailored intervention plans for breast cancer require prioritization within precision prevention to mitigate global breast cancer inequities and burden.
