Troisi Rebecca, Hatch Elizabeth E, Palmer Julie R, Titus Linda, Robboy Stanley J, Strohsnitter William C, Herbst Arthur L, Adam Ervin, Hyer Marianne, Hoover Robert N
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
Department of Epidemiology, Boston University School of Public Health, Boston, MA.
Am J Obstet Gynecol. 2016 Sep;215(3):322.e1-8. doi: 10.1016/j.ajog.2016.03.007. Epub 2016 Mar 12.
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.
We explored whether neoplasia risk remains elevated among DES-exposed women as they age.
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.
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).
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.
产前暴露于己烯雌酚（DES）与阴道和宫颈透明细胞腺癌以及高级别鳞状上皮瘤变的额外风险相关。
我们探讨了暴露于DES的女性随着年龄增长，肿瘤形成风险是否仍然升高。
总共对4062名暴露于DES的女儿和1837名未暴露的女儿进行了约30年（1982年至2013年）的随访，以获取经病理证实的下生殖道宫颈上皮内瘤变≥2级（CIN2+）的诊断（n = 178）。估计了风险比（HR）和95%置信区间（CI），并对出生年份和个体研究队列进行了调整。
暴露于DES组的CIN2+累积发病率为5.3%（95%CI，4.1 - 6.5%），未暴露组为2.6%（95%CI，1.5 - 3.7%）。DES与CIN2+的HR为1.98（95%CI，1.33 - 2.94），在进一步调整宫颈癌筛查频率后相似（HR，1.97；95%CI，1.33 - 2.93）。在对其他潜在混杂因素进行额外调整后，HR为2.10（95%CI，1.41 - 3.13）。DES暴露的HR在44岁之前升高（年龄<45岁时HR，2.47；95%CI，1.55 - 3.94），但在年龄≥45岁的女性中未升高（HR，0.91；95%CI，0.39 - 2.10）。在暴露女性中，与未暴露女性相比，那些早期有阴道上皮变化（VEC）证据的女性（推测反映腺上皮向正常成年型鳞状上皮转化）中DES与CIN2+的HR为1.74（95%CI，1.09 - 2.79），而那些没有VEC的女性中HR为1.24（95%CI，0.75 - 2.06）。对于早期子宫内暴露的女性，DES与CIN2+的HR更高（妊娠<8周时HR，2.64；95%CI，1.64 - 4.25；妊娠≥8周时HR，1.41；0.88 - 2.25），而在暴露开始于第15周之后时最低（HR，1.14；95%CI，0.59 - 2.20）。
暴露于DES的女性中CIN2+发病率更高，尤其是那些早期妊娠暴露和有VEC的女性。DES与CIN2+的HR在40多岁中期之前一直为阳性且显著，证实了对这些女性进行年度细胞学筛查的建议是合适的。年龄≥45岁的女性是否继续需要增加筛查尚不清楚，这需要仔细权衡可能的风险和益处。
