Women exposed to DES before birth (in the womb), known as DES Daughters, are at increased risk for clear cell adenocarcinoma of the vagina and cervix, but the effect of in utero DES exposure on later development of squamous neoplasia in the cervix and vagina is uncertain. This combined follow-up study of 3,899 DES Daughters (median age 38) and 1,374 unexposed daughters (median age 39) was followed 1982-1995. Subjects were drawn from three previously studied cohorts (DESAD, Dieckmann, and Horne). The purpose was to examine the long-term risk of developing high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract in DES Daughters compared with unexposed daughters.

The study found a small but significant increase in HSIL among DES Daughters in all age groups, including those over age 40. A total of 111 pathology-confirmed HSIL cases occurred, including five of the vagina, one of the vulva and two cases of invasive cervical cancer. The overall relative risk was 2.1 among DES-exposed versus unexposed. The relative risk among those whose mothers were prescribed DES within 7 weeks of the last menstrual period was 2.8 compared with 1.35 among women exposed for the first time at 15 weeks or later. Women with documented high-grade neoplasia before 1982 were excluded because prior treatment of the cervix may lower the subsequent finding of intraepithelial neoplasia. Researchers could not rule out that more frequent and intensive screening among DES-exposed women played a role in these findings.

Neoplasia is abnormal and uncontrolled cell growth; a neoplasm is new growth of benign or malignant tissue. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. These flat cells look like fish scales under a microscope. Squamous intraepithelial lesion (SIL) is a general term for the abnormal growth of squamous cells on the surface of the cervix. The changes in the cells are described as low grade or high grade, depending on how much of the cervix is affected and how abnormal the cells appear. Cervical intraepithelial neoplasia (CIN) is a general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. High-grade squamous intraepithelial lesion (HSIL) is a precancerous condition in which the cells of the uterine cervix are moderately or severely abnormal. In this study, grades 2 and 3 were considered high. (Adapted from National Cancer Institute Dictionary, available at URL: http://cancer.gov/dictionary/)

Citation: Hatch EE, Herbst AL, Hoover RN, Noller KL, Adam E, Kaufman RH, et al. Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol [United States]. Cancer Causes Control 2001;12:837-845.