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Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract.

Publication ,  Journal Article
Troisi, R; Hatch, EE; Palmer, JR; Titus, L; Robboy, SJ; Strohsnitter, WC; Herbst, AL; Adam, E; Hyer, M; Hoover, RN
Published in: Am J Obstet Gynecol
September 2016

BACKGROUND: Prenatal diethylstilbestrol (DES) exposure is associated with an excess risk of clear-cell adenocarcinoma of the vagina and cervix, and of high-grade squamous neoplasia. OBJECTIVE: We explored whether neoplasia risk remains elevated among DES-exposed women as they age. STUDY DESIGN: In all, 4062 DES-exposed and 1837 unexposed daughters were followed for approximately 30 years (1982 through 2013) for pathology-confirmed diagnoses of cervical intraepithelial neoplasia grade ≥2 (CIN2+) of the lower genital tract (n = 178). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated adjusting for birth year and individual study cohort. RESULTS: The cumulative incidence of CIN2+ in the DES-exposed group was 5.3% (95% CI, 4.1-6.5%) and in the unexposed group was 2.6% (95% CI, 1.5-3.7%). The HR for DES and CIN2+ was 1.98 (95% CI, 1.33-2.94), and was similar with further adjustment for frequency of cervical cancer screening (HR, 1.97; 95% CI, 1.33-2.93). The HR was 2.10 (95% CI, 1.41-3.13) with additional adjustment for other potential confounders. The HR for DES exposure was elevated through age 44 years (age <45 years HR, 2.47; 95% CI, 1.55-3.94), but not in women age ≥45 years (HR, 0.91; 95% CI, 0.39-2.10). In exposed women, HRs for DES were 1.74 (95% CI, 1.09-2.79) among those who had earlier evidence of vaginal epithelial changes (VEC), presumably reflecting glandular epithelium undergoing transformation to normal, adult-type squamous epithelium, and 1.24 (95% CI, 0.75-2.06) among those without VEC, compared with unexposed women. The HRs for DES and CIN2+ were higher among women with earlier intrauterine exposure (HR, 2.64; 95% CI, 1.64-4.25 for <8 weeks' gestation and HR, 1.41; 0.88-2.25 for ≥8 weeks' gestation), and lowest when exposure began >15th week (HR, 1.14; 95% CI, 0.59-2.20). CONCLUSION: CIN2+ incidence was higher among the DES exposed, particularly those with early gestational exposure and VEC. The HR for DES and CIN2+ remained positive and significant until the mid-40s, confirming that the recommendation of annual cytological screening among these women is appropriate. Whether those ≥45 years of age continue to require increased screening is unclear, and would require a careful weighing of possible risks and benefits.

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Published In

Am J Obstet Gynecol

DOI

EISSN

1097-6868

Publication Date

September 2016

Volume

215

Issue

3

Start / End Page

322.e1 / 322.e8

Location

United States

Related Subject Headings

  • Vaginal Smears
  • Uterine Cervical Neoplasms
  • Uterine Cervical Dysplasia
  • Risk
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Papanicolaou Test
  • Obstetrics & Reproductive Medicine
  • Middle Aged
  • Incidence
 

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Troisi, R., Hatch, E. E., Palmer, J. R., Titus, L., Robboy, S. J., Strohsnitter, W. C., … Hoover, R. N. (2016). Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. Am J Obstet Gynecol, 215(3), 322.e1-322.e8. https://doi.org/10.1016/j.ajog.2016.03.007
Troisi, Rebecca, Elizabeth E. Hatch, Julie R. Palmer, Linda Titus, Stanley J. Robboy, William C. Strohsnitter, Arthur L. Herbst, Ervin Adam, Marianne Hyer, and Robert N. Hoover. “Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract.Am J Obstet Gynecol 215, no. 3 (September 2016): 322.e1-322.e8. https://doi.org/10.1016/j.ajog.2016.03.007.
Troisi R, Hatch EE, Palmer JR, Titus L, Robboy SJ, Strohsnitter WC, et al. Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. Am J Obstet Gynecol. 2016 Sep;215(3):322.e1-322.e8.
Troisi, Rebecca, et al. “Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract.Am J Obstet Gynecol, vol. 215, no. 3, Sept. 2016, pp. 322.e1-322.e8. Pubmed, doi:10.1016/j.ajog.2016.03.007.
Troisi R, Hatch EE, Palmer JR, Titus L, Robboy SJ, Strohsnitter WC, Herbst AL, Adam E, Hyer M, Hoover RN. Prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. Am J Obstet Gynecol. 2016 Sep;215(3):322.e1-322.e8.
Journal cover image

Published In

Am J Obstet Gynecol

DOI

EISSN

1097-6868

Publication Date

September 2016

Volume

215

Issue

3

Start / End Page

322.e1 / 322.e8

Location

United States

Related Subject Headings

  • Vaginal Smears
  • Uterine Cervical Neoplasms
  • Uterine Cervical Dysplasia
  • Risk
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Papanicolaou Test
  • Obstetrics & Reproductive Medicine
  • Middle Aged
  • Incidence