Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States)

Cancer Causes Control. 2001 Nov;12(9):837-45. doi: 10.1023/a:1012229112696.


Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES.

Methods: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates.

Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis.

Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

MeSH terms

  • Carcinoma, Squamous Cell / chemically induced*
  • Carcinoma, Squamous Cell / epidemiology
  • Cohort Studies
  • Diethylstilbestrol / adverse effects*
  • Estrogens, Non-Steroidal / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Middle Aged
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Factors
  • Time Factors
  • United States / epidemiology
  • Uterine Cervical Neoplasms / chemically induced*
  • Uterine Cervical Neoplasms / epidemiology
  • Vaginal Neoplasms / chemically induced*
  • Vaginal Neoplasms / epidemiology


  • Estrogens, Non-Steroidal
  • Diethylstilbestrol