Endometrial cancer incidence and mortality rates have increased significantly among women in the U.S [1,2]. These increases have been primarily attributed to rates of non-endometrioid carcinomas (including serous, carcinosarcoma, and clear cell), which are particularly high among Non-Hispanic Black women. Rates of endometrioid carcinomas have also increased among certain groups, likely associated with rising rates of obesity [1]. As a group, non-endometroid carcinomas account for approximately 20 % of all endometrial cancer cases but 45 % of all endometrial cancer deaths [2]. In contrast, endometrioid carcinomas account for approximately 80 % of cases and generally have a favorable prognosis. Lifetime estrogen exposure and metabolic dysregulation are well-established risk factors for endometrial endometrioid carcinoma; however, specific risk factors associated with non-endometrioid histotypes are not well understood [[3], [4], [5]].

Over the past decade, endometrial cancer classification and risk stratification have undergone a major shift from a binary system broadly based on etiology to a molecularly informed classification based on histotype and molecular subtype [6]. The Cancer Genome Atlas (TCGA) and subsequent clinical validation studies identified four distinct molecular subgroups with prognostic and predictive significance, including: [1] ultramutated tumors with somatic mutations in the exonuclease domain of DNA polymerase epsilon (POLE-mut) [2], hypermutated tumors with mismatch repair deficiency (MMRd) [3], copy number high tumors with alterations and mutations in TP53 (p53abn), and [4] copy number low tumors without above alterations designated as no specific molecular profile (NSMP) [[7], [8], [9]]. The distribution of these molecular subtypes is strongly related to histotype, with nearly all serous carcinomas and carcinosarcomas classified as p53abn and nearly all POLE-mut and MMRd tumors having endometrioid histology [10]. Although cancer registries currently lack detailed molecular information, population-based analyses of endometrial cancer histotypes can advance our understanding about the epidemiology of this disease beyond the traditional binary classification system. To this end, we conducted a population-based analysis of hysterectomy-corrected, age-specific endometrial cancer incidence rates and five-year relative survival by histotype and race and ethnicity in the Surveillance, Epidemiology, and End Results (SEER) database among cases diagnosed from 2000 to 2019.