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Age-period-cohort analysis involves 3 temporal factors: age (the length of time from birth to diagnosis), period (the calendar time of diagnosis), and cohort (the calendar time of birth). The application of age-period-cohort analysis in disease forecasting can help researchers and health authorities anticipate future disease burden. In this study, a synthesized age-period-cohort prediction method was proposed based on 4 assumptions: 1) no single model can dominate as the most accurate prediction model in all forecasting scenarios; 2) historical trends will not continue indefinitely; 3) a model with the most accurate forecast for the training data will also be appropriate for forecasting future data; and 4) a model dominated by the stochastic temporal change will be the best-selected model with the robust forecasting. An ensemble of age-period-cohort prediction models was constructed, and Monte Carlo cross-validation was performed to evaluate forecasting accuracy of these models. Data on lung cancer mortality from 1996 to 2015 in Taiwan were used and projected to the year 2035 to illustrate the method. The actual lung cancer mortality rates from 2016 to 2020 were then used to verify the forecasting accuracy. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women in Taiwan. The age-standardized incidence rate has doubled in just 20 years, causing considerable concern to health professionals and the general public. This study used an ensemble of age-period-cohort models to estimate breast cancer incidence trends in Taiwan from 1997 to 2016 and project trends up to 2035. The (truncated) world standard population (World Health Organization 2000) proportions (age groups: 25–29, 30–34, ..., 80–84, and older than 85 years) were used to calculate age-standardized incidence rates. The age-standardized incidence rate from 1997 (60.33/100,000 population) to 2016 (128.20/100,000 population) increased rapidly. The projection is that the increase in the age-standardized incidence will subsequently slow and exhibit a plateau in 2031 (151.32/100,000 population). From 2026 to 2035, the age-specific incidence rates for women older than 55 years old (postmenopausal breast cancer) are projected to increase with larger percentage increments for older women. A future leveling of female breast cancer incidence trends in Taiwan is anticipated. The majority of the patients with breast cancer in the future will be women aged 55 years and older. Education on lifestyle recommendations and mammography screening is required to reduce the burden of breast cancer. The results should have implications for other countries which are also confronted with the same public health problem of rapidly increasing breast cancer incidences. [ABSTRACT FROM AUTHOR]

Oral cancer is the fourth most common cancer among men in Taiwan. The age-standardized incidence rate of oral cancer among men in Taiwan has increased since 1980 and became six times greater in 2014. To enable effective public health planning for oral cancer, research on the projection of oral cancer burden is essential. We conducted an age-period-cohort analysis on the incidence of oral cancer among men in Taiwan from 1997 to 2017 and extrapolated the trend to 2025. We found that the period trends for young adults aged between 25 and 44 have already peaked before 2017; the younger, the earlier, and then the trends declined. The cohort trends have peaked roughly at the 1972 birth cohort and then declined for all ages. Despite the increasing trend in the age-standardized incidence rate for oral cancer among men in Taiwan from 1997 to 2017, we forecast a peak attained, an imminent decline after 2017, and a decrease of 8.4% in age-standardized incidence rate from 2017 to 2025. The findings of this study contribute to developing efficient and comprehensive strategies for oral cancer prevention and control. [ABSTRACT FROM AUTHOR]

Background: Globally, the morbidity and mortality rates for chronic liver disease and cirrhosis are increasing. The National Viral Hepatitis Therapy Program in Taiwan was implemented in 2003, but evidence regarding the program's effect on the trends of mortality for chronic liver disease and cirrhosis is limited. Methods: We analyzed mortality rates for chronic liver disease and cirrhosis in Taiwan for the period from 1981 to 2015. An autoregressive age–period–cohort model was used to estimate age, period, and cohort effects. Results: Age-adjusted mortality rates for chronic liver disease and cirrhosis all displayed a flat but variable trend from 1981 to 2004 and a decreasing trend thereafter for both sexes. The age–period–cohort model revealed differential age gradients between the two sexes; mortality rates in the oldest age group (90–94 years) were 12 and 66 times higher than those in the youngest age group (30–34 years) for men and women, respectively. The period effects indicated that mortality rates declined after 2004 in both sexes. Mortality rates decreased in men but increased in women in the 1891–1940 birth cohorts and increased in both sexes in the birth cohorts from 1950 onward. Conclusions: The National Viral Hepatitis Therapy Program in Taiwan may have contributed to the decrease in mortality rates for chronic liver disease and cirrhosis in adulthood. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most common malignancies involving the urinary system of about 1.65 million cases worldwide. To attain the 25 by 25 goal set by the World Health Organization (25% reduction in non-communicable diseases between 2015 and 2025), developing strategies to reduce cancer burdens is essential. The data of the study comprised the age-specific bladder cancer cases and total population numbers from age 25 to 85 and above from 1997 to 2016 in Taiwan. An ensemble age–period–cohort model was used to estimate bladder cancer incidence trends and forecast the trends to 2025. For men, the projected age-standardized incidence rates per 100,000 people in 2020 and 2025 are 13.0 and 10.4, respectively, with a 16.1% and 32.9% decrease projected from 2016 to 2020 and 2025, respectively. For women, the projected age-standardized incidence rates per 100,000 people in 2020 and 2025 are 4.7 and 3.7, respectively, with a 16.1% and 33.9% decrease projected from 2016 to 2020 and 2025, respectively. The age-specific bladder cancer incidence rates demonstrated a consistently downward trend after 2003 for all ages and both sexes. This study projects that the incidence rates of bladder cancer in Taiwan will continue to decrease, and more than a 25% reduction can be achieved from 2016 to 2025. [ABSTRACT FROM AUTHOR]

Purpose: To reduce colorectal cancer morbidity and mortality in Taiwan, a nationwide screening program with fecal immunochemical test was implemented from January 2004. This study evaluated the influence of this screening program through the controlled interrupted time series analysis. Methods: The controlled interrupted time series analysis was performed using the Poisson regression model with simple linear spline function adjusted for 5-year age-groups and the birth cohort. A sensitivity analysis was performed to re-estimate the effect of the screening program. Results: The expected age-adjusted colorectal cancer mortality rates (by setting the effect of the screening program to zero) for both genders were close to the observed rates during 2004–2013 and were dramatically higher than the observed rates thereafter. The average annual percent changes in colorectal cancer mortality revealed an increasing trend for the age-groups 0–49 and ≥ 75 years and a decreasing trend for the age-groups 50–69 and 70–74 years for 2014–2017. Compared with 1991–2003, the adjusted mortality rate ratios were 0.93 (0.86–1.00) and 1.07 (1.00–1.15) in 2014–2017 for the screening and control groups. Regarding the percent changes, reductions of 7.49% between 1991–2003 and 2014–2017 and 14.76% between the control and screening groups were observed. Conclusion: The nationwide screening program effectively reduced colorectal cancer mortality. Including individuals aged 70–74 years into the target population of the screening program as well as including medical centers and clinics in the program to promote the screening test effectively reduced colorectal cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Air pollution is a global public health concern. The World Health Organization has recently set up a goal of saving 7 million people globally by 2030 from air pollution related death. We conducted an ecological study of geographical variation to explore the association between air pollution (specifically, particulate matter <2.5 μm in aerodynamic diameter [PM2.5], particulate matter <10 μm in aerodynamic diameter, sulfur dioxide, nitrogen dioxide, nitric oxide, and ozone) and cancer incidence in Taiwan, from 2012 to 2016.Methods: In this study, the yearly average concentrations of each air pollutant at 75 air quality monitoring stations were calculated, and using the kriging method, the concentrations were extrapolated to each and every geographical central point of 349 local administrative areas of Taiwan. Spearman rank correlation coefficients between the age-adjusted cancer incidence rates and various air pollutants were calculated by stratifying genders and urbanization degrees of the local administrative areas. A total of 70 correlation coefficients were calculated.Results: In total, 17 correlation coefficients were significantly positive at an alpha level of 0.05. Among these, four correlation coefficients between the age-adjusted cancer incidence rates and PM2.5 levels remained significant after Bonferroni correction. For men in developing towns, general towns, and aged towns and for women in aged towns, the age-adjusted cancer incidence rates increased 13.1 (95% confidence interval [CI], 8.8-17.6), 11 (95% CI, 5.6-16.4), 16.7 (95% CI, 6.9-26.4), and 11.9 (95% CI, 5.6-18.2) per 100,000 populations, respectively, for every 1 μg/m3 increment in PM2.5 concentrations.Conclusions: A significantly positive correlation was observed between the PM2.5 level and cancer incidence rate after multiple testing correction. [ABSTRACT FROM AUTHOR]

Background: Projections on liver diseases mortality can provide a basis for evaluating the World Health Organization's "25 by 25" goal and can help healthcare systems design appropriate control strategies. This study evaluated whether the 25 by 25 goal can be achieved in Taiwan and discussed possible future control strategies. Methods: Age‐period‐cohort models are used to estimate the mortality trends of liver diseases from 1981 to 2016 and project these trends to 2035. Results: For chronic liver disease and cirrhosis among men, the age‐adjusted mortality rate decreased from 1981 to 1991, increased until 1999, and subsequently decreased again until 2016. For women, the age‐adjusted mortality rate exhibited an increasing but up‐and‐down trend from 1981 to 1998 and a decreasing trend to 2016. For liver cancer among men, the age‐adjusted mortality rate exhibited an increasing trend from 1981 to 2002 and a decreasing trend to 2016. For women, the age‐adjusted mortality rate exhibited an increasing trend from 1981 to 2003 and a decreasing trend to 2016. The age‐adjusted mortality rates of chronic liver disease, cirrhosis and liver cancer for both sexes are projected to decrease by more than 30% from 2016 to 2025 and by more than 55% from 2016 to 2035. Conclusion: These results indicated that the 25 by 25 goal can be achieved for liver diseases mortality in Taiwan. In addition to viral hepatitis, the following risk factors may become the major causes of liver diseases in Taiwan in the future: alcohol and tobacco use, diabetes and obesity. [ABSTRACT FROM AUTHOR]

Cervical, endometrial, and ovarian cancers are major gynecologic cancers in Taiwan. Although cervical cancer has received attention through nationwide screening program and the rollout of the human papillomavirus vaccine, endometrial and ovarian cancers have attracted less attention. The age–period–cohort analysis of constant-relative-variation method was used to estimate the mortality trends of cervical, endometrial, and ovarian cancers for population aged 30–84 years during 1981–2020 in Taiwan. The years of life lost was used to estimate the disease burden due to premature death from gynecological cancers. The age effect of endometrial cancer mortality was greater than those of cervical and ovarian cancers. The period effects decreased during 1996–2000 for cervical cancer and plateaued for endometrial and ovarian cancers during 2006–2020. The cohort effect decreased after the birth year 1911 for cervical cancer, increased after 1931 for endometrial cancer, and increased in all birth years for ovarian cancer. For both endometrial and ovarian cancers, the Spearman's correlation coefficients revealed the strong negative correlations between the fertility and the cohort effects, and the strong positive correlations between the average age at first childbirth and the cohort effects. The burden of premature death from ovarian cancer was higher than those of cervical and endometrial cancers during 2016–2020. Due to increasing cohort effect and burden of premature death, endometrial and ovarian cancers will become the largest threat to women's reproductive health in Taiwan. • Cervical cancer is no longer the top gynecological cancer threat to Taiwanese women. • Endometrial cancer had a continuously increasing burden of premature death. • Ovarian cancer had a higher burden of premature death than cervical cancer after 2016. • Cohort effect of endometrial cancer is strong, while that of ovarian cancer is rising. • Endometrial and ovarian cancers will be the most lethal gynecologic cancer in Taiwan. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is the second most common cause of cancer death in developed countries among men (after lung cancer) and the third most common among women. This study thus examines the long-term trends of CRC mortality in Taiwan. Methods: CRC cases were collective between patients aged 30 years or older and younger than 85 years from the Taiwan death registries during 1971-2010. Standard descriptive techniques such as age-standardized mortality rates (ASMR), aural percent change, and age-period-cohort analyses were used. Results: The increase of percentage change by each age group in men was higher than in women. The ASMR of CRC increased 2-fold for men and almost 1.5-fold for women during the periods 1971-1975 and 2006-2010. For age-period-cohort analysis, the estimated mortality rate increased steadily with age in both sexes, and plateaued at 175.29 per 100,000 people for men and 128.14 per 100,000 for women in the 80- to 84-year-old group. Period effects were weak in both sexes. Cohort effects were strong. Between 30 and 59 years of age, the sex ratio showed that the female CRC mortality rate was higher than that of their male counterparts. Conversely, the mortality risk of CRC in men was higher than that in women when they were between 60 and 84 years old. Conclusions: The current findings showed a consistent increase in mortality from CRC over the years. Changes in the patient sex ratio indicated an important etiological role of sex hormones, especially in women aged 60 years or younger. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer in Taiwan. After Taiwan implemented the Tobacco Hazards Prevention Act in 1997, smoking rates declined. However, the incidence rates of lung cancer for both sexes are still increasing, possibly due to risk factors other than smoking. We used age–period–cohort analysis to examine the secular trends of lung cancer incidence rates by histological type in Taiwan. A stabilized kriging method was employed to map these lung cancer incidence rates. Lung adenocarcinoma incidence rates increased, but lung squamous cell carcinoma incidence rates decreased, for both the sexes in recent birth cohorts, particularly in women. In Taiwan, the hotspots of lung adenocarcinoma incidence rates were in the northern, northeastern, and western coastal areas; the incidence rates increased rapidly in the western and southern coastal regions and southern mountainous regions. The high incidence rates of lung squamous cell carcinoma in men were in the southwestern and northeastern coastal areas. The incidence rates rapidly increased in the central and southern coastal and mountainous regions. For both sexes in Taiwan, lung squamous cell carcinoma incidence rates declined from 1997 to 2017, but lung adenocarcinoma increased. The increased incidence rates of lung adenocarcinoma may be related to indoor and outdoor air pollution. Some areas in Taiwan have increasing lung cancer incidence rates, including the northwestern and southern coasts and mountains, and warrant particular attention. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect. [ABSTRACT FROM AUTHOR]

Mapping spacetime disease rates can provide a more in-depth understanding of their distribution and trends. Traditional spatiotemporal kriging methods can break the constraints of geopolitical boundaries and time intervals. Still, disease rates in densely and sparsely populated areas are stabilized to the same degree, resulting in a map that is oversmoothed in some places but undersmoothed in others. The stabilized spatiotemporal kriging method proposed in this study overcomes this problem by allowing for nonconstant variances over space and time. A spatiotemporal map of the standardized incidence ratio for oral cancer in men in Taiwan between 1997 and 2017 reveals that the high-risk areas for oral cancer are in the midwestern and southeastern regions of Taiwan, spreading toward the center and north, with persistent cold spots in the northern and southwestern urban regions. However, the corresponding map for breast cancer in women in Taiwan reveals that the high-risk areas for breast cancer are concentrated in densely populated urban regions in the west. Spatiotemporal maps facilitate our understanding of disease risk dynamics. We recommend using the proposed stabilized spatiotemporal kriging method for mapping disease rates across space and time. [ABSTRACT FROM AUTHOR]

Objectives: Oral cancer is the fourth most common cancer among men in Taiwan. Betel nut consumption is a major risk factor for oral cancer, but the association between betel nut chewing and the long-term secular trend of oral cancer incidence is unclear.Materials and Methods: We conducted an age-period-cohort analysis to examine the incidence rates of oral cancer among men in Taiwan from 1997 to 2016.Results: The oral cancer incidence rate among men doubled between 1997 and 2009, but the trend leveled off thereafter. Oral cancer incidence rates in the oldest age group (80-84y) were approximately 85 times those of the youngest group (25-29y). The period effect was weak, and the cohort effect exhibited a drastically increasing trend from 1917 (midyear for 1913-1921) to 1972 (1968-1976) birth cohorts and then a decreasing trend afterward. The Spearman rank correlation coefficient between the cohort effects on oral cancer incidence among men and the average consumption of betel nut with a lag time of 30 years had a significant and extremely high value of 0.993.Conclusions: Our findings suggest that betel nut chewing is the main driver of the cohort effect for oral cancer incidence rates among men in Taiwan. In addition to reduced betel nut consumption, a decrease in smoking prevalence may also have contributed to the reduction in oral cancer incidence after the 1972 birth cohort; moreover, the increasing prevalence of alcohol consumption in Taiwan is unlikely to be the reason for the cohort effect for oral cancer. [ABSTRACT FROM AUTHOR]

Age-period-cohort analysis of incidence and/or mortality data has received much attention in the literature. To circumvent the non-identifiability problem inherent in the age-period-cohort model, additional constraints are necessary on the parameters estimates. We propose setting the constraint to reflect the different nature of the three temporal variables: age, period, and birth cohort. There are two assumptions in our method. Recognizing age effects to be deterministic (first assumption), we do not explicitly incorporate the age parameters into constraint. For the stochastic period and cohort effects, we set a constant-relative-variation constraint on their trends (second assumption). The constant-relative-variation constraint dictates that between two stochastic effects, one with a larger curvature gets a larger (absolute) slope, and one with zero curvature gets no slope. We conducted Monte-Carlo simulations to examine the statistical properties of the proposed method and analyzed the data of prostate cancer incidence for whites from 1973–2012 to illustrate the methodology. A driver for the period and/or cohort effect may be lacking in some populations. In that case, the CRV method automatically produces an unbiased age effect and no period and/or cohort effect, thereby addressing the situation properly. However, the method proposed in this paper is not a general purpose model and will produce biased results in many other real-life data scenarios. It is only useful in situations when the age effects are deterministic and dominant, and the period and cohort effects are stochastic and minor. [ABSTRACT FROM AUTHOR]

Monitoring survival in cancer is a common concern for patients, physicians, and public health researchers. The traditional cohort approach for monitoring cancer prognosis has a timeliness problem. In this paper, we propose a survivorship-period-cohort (SPC) model for examining the effects of survivorship, period, and year-of-diagnosis cohort on cancer prognosis and for predicting future trends in cancer survival. We used the developed SPC model to evaluate the relative survival (RS) of patients with liver cancer in Taiwan (diagnosed from 1997 to 2016) and to predict future trends in RS by imputing incomplete follow-up data for recently diagnosed patient cohorts. We used cross-validation to select the extrapolation method and bootstrapping to estimate the 95% confidence interval for RS. We found that 5-year cumulative RS increased for both men and women with liver cancer diagnosed after 2003. For patients diagnosed before 2010, the 5-year cumulative RS rate for men was lower than that for women; thereafter, the rates were better for men than for women. The SPC model can help elucidate the effects of survivorship, period, and year-of-diagnosis cohort effects on cancer prognosis. Moreover, the SPC model can be used to monitor cancer prognosis in real time and predict future trends; thus, we recommend its use. [ABSTRACT FROM AUTHOR]

Cancer is a public health problem worldwide. Taiwan has a higher incidence rate of urological cancers than many Asian countries do. Aristolochic acid has been considered a potent carcinogen. In this study, we examined whether the cessation of the sales and preparation of aristolochic acid-containing Chinese herbal products (AA-CHPs) in Taiwan contributed to a decline in the incidence rates of bladder cancer, carcinomas of the renal pelvis and other urinary organs, and kidney cancer. We conducted an interrupted time-series analysis of long-term trends in the incidence rates of the aforementioned cancers between 1995 and 2013 in Taiwan. The incidence rates of bladder cancer and carcinomas of the renal pelvis and other urinary organs decreased considerably after 2008 and 2011, respectively. Notably, these change-of-slope time points occurred after the year 2003, when a ban on AA-CHPs was imposed in Taiwan. The ban on AA-CHPs in Taiwan was possibly associated with the reduction in the incidence of bladder cancer and carcinomas of the renal pelvis and other urinary organs. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997–2016. We used the age–period–cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban–rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have examined the association between heavy metal contamination (including arsenic [As], cadmium [Cd], chromium [Cr], copper [Cu], mercury [Hg], nickel [Ni], lead [Pb], and zinc [Zn]) and lung cancer. However, data from previous studies on pathological cell types are limited, particularly regarding exposure to low-dose soil heavy metal contamination. The purpose of this study was to explore the association between soil heavy metal contamination and lung cancer incidence by specific cell type in Taiwan.Methods: We conducted an ecological study and calculated the annual averages of eight soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) by using data from the Taiwan Environmental Protection Administration from1982 to 1986. The age-standardized incidence rates of lung cancer according to two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]) were obtained from the National Cancer Registry Program conducted in Taiwan from 2001 to 2005. A geographical information system was used to plot the maps of soil heavy metal concentration and lung cancer incidence rates. Poisson regression models were used to obtain the adjusted relative ratios (RR) and 95% confidence intervals (CI) for the lung cancer incidence associated with soil heavy metals.Results: For males, the trend test for lung SCC incidence caused by exposure to Cr, Cu, Hg, Ni, and Zn showed a statistically significant dose-response relationship. However, for lung AC, only Cu and Ni had a significant dose-response relationship. As for females, those achieving a statistically significant dose-response relationship for the trend test were Cr (P = 0.02), Ni (P = 0.02), and Zn (P= 0.02) for lung SCC, and Cu (P < 0.01) and Zn (P = 0.02) for lung AC.Conclusion: The current study suggests that a dose-response relationship exists between low-dose soil heavy metal concentration and lung cancer occurrence by specific cell-type; however, the relevant mechanism should be explored further. [ABSTRACT FROM AUTHOR]