Synthesized Age-Period-Cohort Prediction Method: Application to Lung Cancer Mortality in Taiwan.

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.

Mortality trends and disease burdens of cervical, endometrial and ovarian cancers from 1981 to 2020 in Taiwan.

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.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

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.

A Stabilized Kriging Method for Mapping Disease Rates.

BACKGROUND: Mapping disease rates is an important aspect of epidemiological research because it helps inform public health policy. Disease maps are often drawn according to local administrative areas (LAAs), such as counties, cities, or towns. In LAAs with small populations, disease rates are unstable and are prone to appear extremely high or low. The empirical Bayes methods consider variance differences among different LAAs, thereby stabilizing the disease rates. The methods of kriging break the constraints of geopolitical boundaries and produce a smooth curved surface in the form of contour lines, but the methods lack the stabilizing effect of the empirical Bayes methods. METHODS: An easy-to-implement stabilized kriging method is proposed to map disease rates, which allows different errors in different LAAs. RESULTS: Monte Carlo simulations revealed that the stabilized kriging method had smaller symmetric mean absolute percentage error than three other types of methods (the original LAA-based method, empirical Bayes methods, and traditional kriging methods) in nearly all scenarios considered. Real-world data analysis of oral cancer incidence rates in men from Taiwan demonstrated that the age-standardized rates in the central mountainous sparsely-populated region of Taiwan were stabilized using our proposed method, with no more large differences in numerical values, whereas the rates in other populous regions were not over-smoothed. Additionally, the stabilized kriging map had improved resolution and helped locate several hot and cold spots in the incidence rates of oral cancer. CONCLUSION: We recommend the use of the stabilized kriging method for mapping disease rates.

Birth Cohort Effects in Breast Cancer Incidence: Global Patterns and Trends.

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.

A stabilized spatiotemporal kriging method for disease mapping and application to male oral cancer and female breast cancer in Taiwan.

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.

A Survivorship-Period-Cohort Model for Cancer Survival: Application to Liver Cancer in Taiwan, 1997-2016.

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.

Geographical variations of socioeconomic status and prostate cancer mortality in Taiwan.

PURPOSE: A population-wide study was conducted to determine the association between area-level socioeconomic status and prostate cancer mortality in Taiwan. METHODS: Age-period-cohort analysis was performed to adjust the time-trend variation. The area-level socioeconomic factors included proportion with a higher education, average income tax, population density, and clinical workload. RESULTS: After adjustment for time-trend variations in age, period, and cohort, prostate cancer mortality was significantly lower in the groups with the highest higher education proportion (rate ratio 0.88; 95% Confidence Intervals 0.83-0.93), average income tax (RR 0.90; 95% CIs 0.86-0.94), and population density (RR 0.88; 95% CI 0.83-0.93). When all variables were incorporated into one model, the rate ratio of prostate cancer mortality was 0.92 (95% CIs 0.88-0.97) in the region with the highest average income tax level compared with that with the lowest level, but differences in the other socioeconomic factors were not significant. CONCLUSIONS: This study revealed a significantly lower prostate cancer mortality rate in areas with a high higher education proportion, average income tax level, and population density compared with areas of low socioeconomic status in Taiwan.

Mortality trends in chronic liver disease and cirrhosis from 1981 to 2015 in Taiwan.

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.

Effect of nationwide screening program on colorectal cancer mortality in Taiwan: a controlled interrupted time series analysis.

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.

Mortality trends of liver diseases from 1981 to 2016 and the projection to 2035 in Taiwan: An age-period-cohort analysis.

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.

Associations between ambient air pollution and cancer incidence in Taiwan: an ecological study of geographical variations.

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.

Secular trends in liver cancer incidence from 1997 to 2014 in Taiwan and projection to 2035: An age-period-cohort analysis.

BACKGROUND/PURPOSE: Liver cancer is the second most common cancer in Taiwan. Research on projected cancer incident rates can facilitate appropriate public health planning, and incidence rate studies can offer insights and enable hypotheses about the etiology of particular cancers. METHODS: Age-period-cohort models are used to estimate incidence trends in liver cancer from 1997 to 2014 and project trends up to 2035. RESULTS: For men, the age-adjusted incidence rate showed an increasing trend from 1997, which peaked in 2004 (157.6 cases per 100,000 population), and a decreasing trend thereafter. The age-adjusted incidence rate is projected to decrease by 22.2% from 2014 to 2025 and by 37.3% from 2014 to 2035. For women, the age-adjusted incidence rate also showed an increasing trend from 1997, which peaked in 2004 (63.4 cases per 100,000 population), and a decreasing trend thereafter. The age-adjusted incidence rate is projected to decrease by 17.5% from 2014 to 2025 and by 27% from 2014 to 2035. CONCLUSION: This study revealed a reduction in the incidence rate of liver cancer for both sexes after 2004, and a further decrease until 2035 is projected.

Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

Evidence for cervical cancer mortality with screening program in Taiwan, 1981-2010: age-period-cohort model.

BACKGROUND: Cervical cancer is the most common cancer experienced by women worldwide; however, screening techniques are very effective for reducing the risk of death. The national cervical cancer screening program was implemented in Taiwan in 1995. The objective of this study was to examine and provide evidence of the cervical cancer mortality trends for the periods before and after the screening program was implemented. METHODS: Data from 1981 to 2010 of the causes of death registered were obtained from the Department of Health, Taiwan. Age-standardized mortality rates, age-specific rates, and age-period-cohort models that employed the sequential method were used to assess temporal changes that occurred between 1981 and 2010, with 1995 used as the separating year. RESULTS: The results showed that for both time periods of 1981 to 1995 and 1996 to 2010, age and period had significant effects, whereas the birth cohort effects were insignificant. For patients between 80 and 84 years of age, the mortality rate for 1981 to 1995 and 1996 to 2010 was 48.34 and 68.08. The cervical cancer mortality rate for 1996 to 2010 was 1.0 for patients between 75 and 79 years of age and 1.4 for patients between 80 and 84 years of age compared to that for 1981 to 1995. Regarding the period effect, the mortality trend decreased 2-fold from 1996 to 2010. CONCLUSIONS: The results of this study indicate a decline in cervical cancer mortality trends after the screening program involving Papanicolaou tests was implemented in 1995. However, the positive effects of the screening program were not observed in elderly women because of treatment delays during the initial implementation of the screening program.

Cell-type specificity of lung cancer associated with low-dose soil heavy metal contamination in Taiwan: an ecological study.

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.

Incidence trends and spatial distributions of lung adenocarcinoma and squamous cell carcinoma in Taiwan.

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.

Mortality of colorectal cancer in Taiwan, 1971-2010: temporal changes and age-period-cohort analysis.

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.