Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: Update after 40-year follow-up

Objective Women exposed to diethylstilbestrol (DES) in utero are at increased risk for the development of vaginal and cervical clear cell adenocarcinoma (CCA) at younger age. It is unknown if a second peak will occur in later life, the ages when CCA developed spontaneously in the pre-DES era. The complete epidemiologic curve of CCA has not been reported, yet. Methods We reviewed 720 cases of CCA from the CCA registry at the University of Chicago through 2014. Incidence rates and cumulative risks for CCA were calculated based on white women born in the U.S. from 1948 through 1971. Results In 420 CCA cases there was documented evidence of prenatal DES exposure. 80% were among those between ages 15 and 31 but some occurred as late as age 55. A small second peak occurred around age 42. The risk of DES-related CCA was highest in the 1951–1956 birth cohort and this birth cohort effect closely correlated with DES prescriptions over time in the U.S. (r=0.98, P =0.005). By age 50, the cumulative risk of CCA was 1 per 750 exposed women. CCA cases without evidence of DES exposure had similar ages, year of diagnosis, and birth cohort patterns as the documented DES-exposed cases, suggesting that some negative cases were exposed. Their inclusion raises the cumulative risk of CCA to 1 per 520. Conclusion With the largest data available, our results confirmed the association between prenatal DES exposure and clear cell adenocarcinoma. The study also refines the risks of DES-related CCA.