Role of hormones including diethylstilbestrol (DES) in the pathogenesis of cervical and vaginal intraepithelial neoplasia

Since 1971 several studies have reported the appearance of clear-cell carcinoma and clear-cell cervical carcinoma in young women exposed prenatally to diethylstilbestrol (DES). Several recent reports have been conflicting on this subject. The reported prevalence rate of dysplasia and carcinoma in situ (CIS) range from 0% to 18%, or from 0% to 6% for severe cases. Factors accounting for such discrepancies can be overdiagnosis or a biased selection of patients; as a study of 1424 patients conducted at the Massachusetts General Hospital has shown, the overall rate of severe dysplasia and CIS appeared relatively high only until patients were divided into 2 groups, those referred because of earlier diagnosis of dysplasia, and those screened because of known DES exposure; exclusion from the study of the 1st group reduced the frequency of all grades of dysplasia and CIS to 2.1%, and the rate of severe dysplasia to 0%. The National Collaborative Diethylstilbestrol Adenosis (DESAD) Project has also shown that rates of dysplasia were only 1.83% in DES-exposed daughters while subjects referred for screening exams had rates nearly 3/4 higher. Furthermore, 2 recent studies which compared rates of dysplasia in exposed and nonexposed cohorts showed that dysplasia was found more often in DES-exposed women, while in the DESAD project the prevalence rates were not statistically significant between exposed and nonexposed patients, but the ocurrence of dysplasia was more frequent in older women and in those who had intercourse with increased numbers of partners, a factor which was found to be important also when considering the association between oral contraceptives (OCs) and CIS. Microglandular hyperlasia can also arise in DES-exposed women, but it must not be interpreted as clear-cell adenocarcinoma, and it is associated with long-term use of OCs.