Rebecca Troisi1, Elizabeth E Hatch2, Julie R Palmer3, Linda Titus4, Stanley J Robboy5, William C Strohsnitter6, Arthur L Herbst7, Ervin Adam8, Marianne Hyer9, Robert N Hoover10. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD. Electronic address: troisir@mail.nih.gov. 2. Department of Epidemiology, Boston University School of Public Health, Boston, MA. 3. Slone Epidemiology Unit, Boston University, Boston, MA. 4. Departments of Community and Family Medicine and Pediatrics, Dartmouth Medical School, and the Norris Cotton Cancer Center and the Hood Center for Children and Families, Lebanon, NH. 5. Departments of Pathology and Obstetrics and Gynecology, Duke University Medical Center, Durham, NC. 6. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA. 7. Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL. 8. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX. 9. Information Management Services Inc, Rockville, MD. 10. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
Abstract
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Authors: E E Hatch; A L Herbst; R N Hoover; K L Noller; E Adam; R H Kaufman; J R Palmer; L Titus-Ernstoff; M Hyer; P Hartge; S J Robboy Journal: Cancer Causes Control Date: 2001-11 Impact factor: 2.506
Authors: Julie R Palmer; Elizabeth E Hatch; Carol L Rosenberg; Patricia Hartge; Raymond H Kaufman; Linda Titus-Ernstoff; Kenneth L Noller; Arthur L Herbst; R Sowmya Rao; Rebecca Troisi; Theodore Colton; Robert N Hoover Journal: Cancer Causes Control Date: 2002-10 Impact factor: 2.506
Authors: S J Robboy; W M Szyfelbein; J R Goellner; R H Kaufman; P D Taft; R M Richard; T A Gaffey; J Prat; R Virata; P A Hatab; S P McGorray; K L Noller; D Townsend; D Labarthe; A B Barnes Journal: Am J Obstet Gynecol Date: 1981-07-01 Impact factor: 8.661
Authors: S J Robboy; K L Noller; P O'Brien; R H Kaufman; D Townsend; A B Barnes; J Gundersen; W D Lawrence; E Bergstrahl; S McGorray Journal: JAMA Date: 1984-12-07 Impact factor: 56.272
Authors: D Labarthe; E Adam; K L Noller; P C O'Brien; S J Robboy; B C Tilley; D Townsend; A B Barnes; R H Kaufman; D G Decker; C R Fish; A L Herbst; J Gundersen; L T Kurland Journal: Obstet Gynecol Date: 1978-04 Impact factor: 7.661
Authors: E R Greenberg; A B Barnes; L Resseguie; J A Barrett; S Burnside; L L Lanza; R K Neff; M Stevens; R H Young; T Colton Journal: N Engl J Med Date: 1984-11-29 Impact factor: 91.245
Authors: William C Strohsnitter; Kimberly A Bertrand; Rebecca Troisi; Christopher G Scott; Andrea L Cheville; Robert N Hoover; Julie R Palmer; Celine M Vachon Journal: Int J Cancer Date: 2018-05-02 Impact factor: 7.396
Authors: Rebecca Troisi; Elizabeth E Hatch; Julie R Palmer; Linda Titus; Joshua N Sampson; Xia Xu; Robert N Hoover Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-07-26 Impact factor: 4.254
Authors: Rebecca Troisi; Marianne Hyer; Linda Titus; Julie R Palmer; Elizabeth E Hatch; Dezheng Huo; Kjersti M Aagaard; William C Strohsnitter; Robert N Hoover Journal: J Dev Orig Health Dis Date: 2020-10-28 Impact factor: 3.034