Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

Objective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear.
Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA invasive cervical cancer in a prospective cohort of 12,182 women with self-reported DES exposure followed from 2000 till 2008. We took screening behavior carefully into account. Incidence was obtained through linkage with the Netherlands Nationwide Pathology database (PALGA). General population data were also derived from PALGA.
Results: The incidence of CIN1 was increased (Standardized Incidence Ratio (SIR). =2.8, 95% Confidence Interval (CI). =2.3 to 3.4), but no increased risk was observed for CIN2. + (CIN2, CIN3 or invasive cancer) compared to the screened general population (SIR. =1.1, 95% CI. =0.95 to1.4). Women with DES-related malformations had increased risks of both CIN1 and CIN2. + (SIR. =4.1, 95%CI. =3.0 to 5.3 and SIR. =1.5, 95%CI. =1.1 to 2.0, respectively). For CIN2. +, this risk increase was largely restricted to women with malformations who were more intensively screened.
Conclusions: An increased risk of CIN1 among DES daughters was observed, especially in women with DES-related malformations, probably mainly due to screening. The risk of CIN2. + (including cancer) was not increased. However, among DES daughters with DES-related malformations a true small risk increase for non-CCA cervical cancer cannot be excluded.