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.

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.

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.

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.

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.

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.

Evaluation of Nationwide Oral Mucosal Screening Program for Oral Cancer Mortality among Men in Taiwan.

The nationwide oral cancer screening program was launched for high-risk people (tobacco smokers or betel-nut chewers) in 1999 in Taiwan, but no study has taken the prevalence of tobacco smoking and betel-nut chewing into account for evaluating the impact of the screening program on oral cancer mortality. This study incorporated the risk fraction method with interrupted time-series analysis to evaluate the impact of the nationwide oral mucosal screening program among men in Taiwan. This study estimated the expected oral cancer mortality trend if the screening program had not launched in 1999, which revealed that the increasing oral cancer mortality trend would level off after 2009 due to the declining prevalence of tobacco smoking and betel-nut chewing. In 2000-2007, the percentage changes between the observed (implementation of the screening program) and expected (if the screening program had not launched) oral cancer mortality rate was not statistically significant for each age group. In 2008-2020, the significant percentage changes were -178% (99% CIs: -140.8 to -215.2), -75.4% (-59.4 to -91.4), -33.7% (-24.7 to -42.7), -18.8% (-12.0 to -25.6), and -15.3% (-9.5 to -21.2) for age groups of 30-34, 35-39, 40-44, 45-49, and 50-54, respectively. In addition to its influence on tobacco smoking and betel-nut chewing, the oral mucosal screening program was associated with the reduction of oral cancer mortality among men in Taiwan.

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.

Forecast of a future leveling of the incidence trends of female breast cancer in Taiwan: an age-period-cohort analysis.

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.

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.

Forecast of peak attainment and imminent decline after 2017 of oral cancer incidence in men in Taiwan.

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.

Nationwide mammographic screening and breast cancer mortality in Taiwan: an interrupted time-series analysis.

BACKGROUND: In Taiwan, breast cancer is the third leading cause of cancer death in women. A nationwide screening program with biennial mammography for women aged 40-69 in Taiwan was implemented since July 2004, but the impact on breast cancer mortality has not been investigated. METHODS: The interrupted time-series analysis was used to estimate the impact of mammographic screening on temporal trends of breast cancer mortality and to calculate the level of temporal changes due to the mammographic screening. RESULTS: The annual average percentage changes of the age-standardized breast cancer mortality rates for all women aged 40-69 were 1.06% from 1991 to 2004 (before mammographic screening) and 0.33-0.34% from 2005 to 2019 (after mammographic screening). For all women aged 40-69, the results of interrupted time-series analysis showed that the increasing trends of breast cancer mortality were all attenuated after the implementation of mammographic screening. An estimation of 2114 women prevented from death of breast cancer may be attributable to screening. For women aged 40-44, 55-59, 60-64 and 65-69, the percentage changes in mortality rates were - 12.1% (- 5.1 to - 19.6%), - 20.8% (- 16.5 to - 25.2%), - 12.8% (- 8.5 to - 17.3%) and - 13.0% (- 7.9 to - 18.3%), respectively, after screening. For women aged 45-49 and 50-54, the reduction of deaths and mortality rates of breast cancer were a little. CONCLUSIONS: This study revealed that the nationwide screening program with biennial mammography may be associated with the attenuation of breast cancer mortality trends in women aged 40-69 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.

Ensemble forecasting of a continuously decreasing trend in bladder cancer incidence in Taiwan.

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.

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.

Oral cancer incidence rates from 1997 to 2016 among men in Taiwan: Association between birth cohort trends and betel nut consumption.

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.