Second primary malignancies in cervical cancer and endometrial cancer survivors: a population-based analysis

Background: We evaluated the relative attribution and interactions of treatment and patient-related risk factors for second primary malignancies (SPMs) in cervical and endometrial cancer survivors. Methods: Stage I–III cervical and endometrial cancer survivors’ data from the Surveillance, Epidemiology, and End Results (SEER) registry between January 1988 and December 2015 were analyzed. The standardized incidence ratio (SIR), excess absolute risk (EAR), and corresponding 95% confidence interval (95% CI) values were calculated. Analyses were classified based on proxies of human papillomavirus (HPV), smoking, hormone, and radiotherapy (RT) status. Additive and multiplicative interactions were assessed. Results: Cervical cancer survivors had a higher risk for developing potentially HPV and smoking-related SPMs, especially in the RT group (SIR(HPV) = 3.7, 95% CI: 2.9–4.6; SIR(smoking) = 3.2, 95% CI: 2.8–3.6). Second vaginal cancer patients had the highest SIR (23.8, 95% CI: 14.9–36.0). There were strong synergistic interactions between RT and the proxy of smoking (P(interaction) < 0.001), accounting for 36% of potentially smoking-related SPMs in cervical cancer survivors. Conclusions: RT, HPV, and smoking promote SPMs in cervical cancer to different extents. The SPM burden in cervical cancer survivors could be mostly attributed to smoking and RT and their interactions.