As a means of studying possible long term effects of in utero exposure to diethylstilbestrol (DES), this application describes a pilot study to determine if women exposed prenatally to DES have an increased prevalence of infection with Human papillomavirus (HPV). Several prior studies, many with significant bias, have reported an increased prevalence or incidence of cervical and vaginal neoplasia in DES exposed women, which if true, could have substantial health consequences. In the United States alone it is estimated that two million women were exposed to DES in utero from 19451971. This cohort has recently reached the age where the age associated prevalence of carcinoma in situ of the cervix is near its peak. A proposed explanation for an increased risk of squamous neoplasia in these women is a predisposition to infection with a sexually transmitted oncogenic agent including HPV. This project will entail a 2 year cohort study of women recruited from the Dieckmann study of individuals exposed prenatally to DES or placebo in 1951-1952. Subjects will complete a confidential questionnaire with emphasis on risk factors associated with HPV infection or dysplasia. A thorough colposcopic examination will document clinical evidence of HPV infection and extent of abnormal cervical and vaginal epithelial changes (VEC). In addition to routine Pap smears, duplicate smears will be collected for subsequent blinded analysis. DNA from cervicovaginal swabs will be analyzed for the presence of type specific HPV by the polymerase chain reaction (PCR). A blood sample from each subject will be analyzed for the presence of IgG antibodies to Herpes simplex virus (HSV). Stepwise linear regression analysis will be used to search for an association between HPV infection and DES exposure. Possible correlations between HPV infection and evidence of other prior viral infections, extent of VEC, or abnormal cytology will be sought. In order to detect a 1.5 fold difference in the prevalence of HPV infection between DES exposed and unexposed women, approximately 110 individuals from each group will be required (alpha (two-tailed) = 0.05; beta = 0.20). Many women from the Dieckmann cohort reside in the Chicago area, and recruitment of a sufficient sample for this study is anticipated.
