Association of Combined Tobacco Smoking and Oral Contraceptive Use With Cervical Intraepithelial Neoplasia 2 or 3 in Korean Women

Background: Cigarette smoking and oral contraceptive (OC) use have been associated with cervical neoplasia, and the combination of smoking and OC use could influence cervical carcinogenesis. We aimed to assess the joint effect of smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN). Methods: From a cohort of human papillomavirus-positive subjects recruited from 6 hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411 control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean age, 43 years). The risk of CIN associated with smoking and OC use on additive and multiplicative scales was estimated via multinomial logistic regression after adjustment for potential confounding factors. The relative excess risk due to interaction (RERI) and the synergy index (S) were used to evaluate the additive interaction. Results: OC users (odds ratio [OR] 1.98; 95% confidence interval [CI], 1.07-3.69) and long-term OC use (>= 20 months; OR 2.71; 95% CI, 1.11-6.59) had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non-OC users. Smokers and heavy smoking (>= 8 cigarettes/day) were not associated with any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68-14.4; RERI/S, 3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking and long-term OC use (OR 11.5; 95% CI, 1.88-70.4; RERI/S, 9.93/18.8; P for multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no association with CIN 1 compared to combined non-smoking and non-OC use. Conclusions: OC use and smoking acted synergistically to increase the risk of CIN 2 or 3 in Korean women.