Epithelial ovarian cancer histotype distributions by race/ethnicity in Kaiser Permanente Northern California, 2000-2022

Background: The 2014 and 2020 World Health Organization (WHO) diagnostic classification guidelines for epithelial ovarian cancer (EOC) standardized histotype classification, improved reproducibility across pathologists, and revealed distinct survival differences by histotype. EOC histotype distributions have not been characterized by racial/ethnic groups on a population level using these updated guidelines. We performed centralized pathology review using the WHO 2020 guidelines to characterize distributions of EOC histotypes across Black, Hispanic, non-Hispanic (NH) Asian and Pacific Islander (API), and NH white groups. Methods: The Kaiser Permanente Research on Ovarian Cancer Survival study includes 6,067 EOC cases ages 18 years and older diagnosed in 2000-2022 who received care for their EOC at Kaiser Permanente Northern California. Original diagnostic slides were centrally reviewed using 2020 WHO guidelines for a subset of 2,470 cases (median 8 slides/patient, range 1-80). Slides for 20 cases did not contain tumor, and 109 were determined not to be EOC, leaving 2,341 cases for analysis. We assessed concordance of the distribution of EOC histotypes before (original diagnosis) and after re-review by calculating unweighted Cohen's Kappa for the cohort overall, and separately for racial/ethnic groups. Results: Overall there was substantial agreement of histotype assignment between the original diagnosis and the pathologist's review (Kappa = 0.67). Agreement varied across racial/ethnic groups, with substantial agreement for NH API (n=640), Hispanic (n=522), and NH white groups (n=928; Kappas 0.73, 0.67, and 0.61, respectively), but moderate agreement for Black individuals (n=242; Kappa 0.59). Overall, proportions of the histotypes before and after study review increased for high grade serous (HGSC) from 58% to 62%; 14% to 17% for endometrioid; 2% to 3% for low grade serous; decreased for carcinoma, NOS from 5% to 0.6% and for grouped rare EOC histotypes including mixed from 4% to 2%; and were unchanged for clear cell, mucinous, and carcinosarcoma (9%, 4%, and 3%, respectively). The highest proportion of HGSC was among Black individuals (73%), and the lowest among NH API individuals (50%), with similar prevalences for Hispanic and NH white individuals (64% and 66%, respectively). Endometrioid, clear cell, and mucinous histotypes were more common among NH API individuals (23%, 14%, and 6%, respectively) compared with the other groups (ranges of 12-16%, 6-8%, and 2-3%, respectively). Conclusions: Improved histotype assignment using WHO 2020 refined distinct differences in histotype distributions by race/ethnicity. Specifically, Black individuals are more likely to be diagnosed with the aggressive HGSC histotype, whereas among NH API individuals non-HGSC histotypes were more common, specifically clear cell, endometrioid, and mucinous histotypes.