Castle Philip E, Wacholder Sholom, Lorincz Attila T, Scott David R, Sherman Mark E, Glass Andrew G, Rush Brenda B, Schussler John E, Schiffman Mark
National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 2002 Sep 18;94(18):1406-14. doi: 10.1093/jnci/94.18.1406.
In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies.
We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided.
Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multivariable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers.
Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.
在病例对照研究中，吸烟、生育状况和口服避孕药的使用与致癌性人乳头瘤病毒（HPV）感染女性发生宫颈上皮内瘤变3级（CIN3）和宫颈癌的风险增加有关。然而，这些潜在风险因素在前瞻性研究中尚未得到充分研究。
我们对1812名女性进行了研究，她们参与了俄勒冈州波特兰市凯撒医疗集团为期10年的宫颈癌前病变前瞻性研究，入组时致癌性HPV DNA检测呈阳性，并对一份包含吸烟、口服避孕药使用和生育状况问题的问卷做出了回应。使用Kaplan-Meier方法计算了三个时间间隔（入组后0 - 8个月、9 - 68个月和69 - 122个月）CIN3或宫颈癌的绝对风险和粗相对风险（RRs）及95%置信区间（CIs）。使用条件逻辑回归模型来控制可能影响我们风险估计的因素，特别是基线巴氏涂片的细胞学解读、随访期间巴氏涂片的数量、入组年龄、诊断前就诊年龄和诊断年龄。所有统计检验均为双侧检验。
口服避孕药的使用和生育状况与CIN3或宫颈癌的风险无关。与从不吸烟者相比，既往吸烟者、每天吸烟少于一包的女性以及每天吸烟一包或更多的女性在整个随访期间CIN3或宫颈癌的粗RRs分别为2.1（95% CI = 1.1至3.9）、2.2（95% CI = 1.2至4.2）和2.9（95% CI = 1.5至5.6）。在多变量模型中，与从不吸烟者相比,既往吸烟者、每天吸烟少于一包的女性以及每天吸烟一包或更多的女性发生CIN3或宫颈癌的RRs分别为3.3（9% CI = 1.6至6.7）、2.9（95% CI = 1.4至6.1）和4.3（95% CI = 2.0至9.3）。
吸烟与致癌性HPV感染女性发生浸润性宫颈癌的风险增加有关。后续研究应探讨吸烟在宫颈癌多阶段发病机制中的作用。
