Incidence of Squamous Neoplasia of the Cervix and Vagina in Women exposed prenatally to DES

DES Follow-up Study Summary

The 2001 stuy findings support an association between in-utero DES exposure and high-grade squamous neoplasia.

Women exposed to Diethylstilbestrol (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.

2001 Study Abstract

OBJECTIVES:
Women exposed prenatally to Diethylstilbestrol (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.

Sources

• Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States),NCBI, PMID: 11714112, 2001 Nov;12(9):837-45.
• NCI, DES Follow-up Study Published Papers.

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