The present survey showed that the age-adjusted incidence rates of uterine cancer increased swiftly from 5.3 to 15.2 per 100 000 woman-years between 1998 and 2017. Endometrioid carcinoma accounted for the majority of uterine cancers, and thus, its incidence rates reflected those of all uterine cancers. However, the incidence rates of non-endometrioid carcinoma and uterine sarcoma also increased during the 20-year period. The age-specific incidence of endometrioid carcinoma peaked at 55-60 years of age. In contrast, the incidence rates of non-endometrioid carcinoma continued to increase with age and then plateaued after 60 years of age. Meanwhile, the percentage changes in the incidence of non-endometrioid carcinoma continued to rise with age, particularly among women over 60 years old.
We found that the incidence of endometrioid carcinoma increased rapidly over the past 20 years and the trend has continued without reaching a plateau to date. This fast-rising trend was not observed in other Western or Asian countries [20, 21]. Trends in the incidence of uterine cancer have also varied with the histologic type in other populations [15, 22]. Endometrioid carcinoma (type I) is estrogen-dependent, and obesity is a key driver of temporal trends in its incidence. The prevalence of overweight status and obesity are increasing globally, but the rates vary by country [23, 24]. This variation suggested that different risk profiles and protection factors might be found in different countries . The Nutrition and Health survey conducted in Taiwan (NAHSIT) showed that the location of residence, educational level, and physical activity were correlated with obesity . Three waves of NAHSIT data analyses showed that the percentages of individuals classified as overweight increased from 1993-1996 to 2005-2008, but stabilized between 2005-2018 and 2013. In contrast, over the same time periods, sharp increases were observed in the prevalence of both obesity (11.8%, 17.9%, to 22.1%, respectively) and morbid obesity (0.4%, 0.6%, to 1.4%) in our country . Rubeis et al. and Song et al. found that overweight status in early adulthood was associated with an increased lifetime risk of cancers, including uterine cancer [27, 28]. The prevalence of overweight and obesity also increased among children and adolescents in Taiwan . Moreover, the increasing trends in the prevalence of uterine cancer over the study period were more noticeable among younger women than among older women. Previous studies also reported that the most recent birth cohorts showed the greatest increases in the incidences of uterine cancer, particularly endometrioid carcinoma [29, 30], similar to our findings.
The measurement methods and classifications of obesity have varied widely. The prevalence of obesity among women was 19.3% in our country during 2013-2016, when obesity was defined as a body mass index (BMI) ≥27 kg/m2 . However, when obesity was defined in terms of the percentage of body fat (≥30% body fat for women), the prevalence of obesity largely increased from 40.2–80.8% over the past decade (NAHSIT 1993-1996 to NAHSIT 2005-2008) [31, 32]. Based on the BMI, the prevalence of obesity was only modest in Taiwan, so there was a large discrepancy between the prevalence based on BMI and the prevalence based on body-fat percentage. Regional differences in the prevalence of obesity were also observed in different studies. Some studies suggested that the risk of obesity was higher in Asian populations than in Caucasian populations, when using the same BMI cutoff point [33, 34]. It has been suggested that the percentage and distribution of body fat could be more closely related to obesity-related disorders than the BMI.
We observed that the most rapid increase of AAPCs in the incidence rates of endometrioid carcinoma among women aged 30 to 34 years (1.6% in 1998 and 5.66% in 2017) and among women aged 35 to 39 years (4.12% in 1998 and 11.2% in 2017). The obesity epidemic was partly reflected in the pronounced increases in risk observed in recent birth cohorts. Other potential explanations for the increasing incidence of uterine cancer might be the declining birth rates and a change in parity among Taiwanese women over time. In Taiwan, the average age of women at first delivery increased from 28.8 years in 2008 to 30.9 years in 2018 . The risk of uterine cancer decreased with increasing parity. However, the association between the timing of delivery (mother’s age at first and last births) and the risk of uterine cancer was inconclusive [36-38].
We found that the incidence of non-endometrioid carcinoma also increased significantly. Similarly, in the US, the rates of non-endometrioid cancers rose over time, and the most profound increases were observed among African American women [15, 39, 40]. Serous carcinoma comprised the majority of non-endometrioid carcinoma which mainly arose from the loss of p53 function during its molecular pathogenesis . Although obesity was the most common causative factor addressed in studies on the increasing incidence of uterine cancer, it remains unknown whether obesity contributed to the increasing incidence of histologic types other than endometrioid carcinoma. Early diagnosis of non-endometrioid carcinoma had a minimal impact on the incidence, because the distribution of disease stages in women diagnosed with non-endometrioid carcinoma remained constant in this survey. The distributions of disease stages, grouped according to age at diagnosis, were similar between endometrioid and non-endometrioid carcinomas in this study (data not shown). Other factors that might influence the increasing incidence of uterine cancer should be further explored, rather than focusing solely on obesity.
Younger women and women with early-stage uterine endometrioid carcinoma had better survival rates than their counterparts. The hazard rates for non-endometrioid carcinoma decreased after adjusting age, diagnostic period and stage. This implied that advanced stage with increasing age at diagnosis, not non-endometrioid histology per se, adversely affected prognosis. Stage was still the strongest predictor of survival. The diagnostic period was also identified as a prognostic factor in this survey. Survival improvements could be attributed to more effective and tailored treatments. For example, a potential benefit might have been conferred by the incorporation of adjuvant chemotherapy over the past decade, in patients in advanced stages and women in early stages with high-risk features. Survival might have also been improved by changes in the management of uterine cancer by specialists, like gynecologic oncologists, in Taiwan and other countries .
The main strengths of our study were the national, population-based, cross-sectional design, and the 20-year study period. Moreover, we included all uterine cancers registered in the National Cancer Registry of Taiwan, and we assessed the incidence trends of different histologic types of uterine cancers. Another advantage of this study was that we characterized variations in the incidences of uterine cancer in groups stratified by age, histological type, calendar period of the diagnosis, and particularly, birth cohort. This study also had some limitations. First, it was retrospective in nature, because it was based on registry data. Consequently, we did not have information on factors that could contribute to the development of uterine cancer, like BMI, hormonal therapy use, and reproductive history, including parity, pregnancy duration, and the timing and number of births. Another limitation was the absence of central pathology review, we could only categorize uterine cancers into four groups (endometrioid, non-endometrioid, sarcoma, and others), rather than the more common classifications of types I and II. In addition, we did not assess the prevalence of overweight/obesity or its association with uterine cancer in this study. Finally, the impact of the risk of obesity might have been limited by other confounders, such as the use of oral contraceptives.