Research Paper Volume 14, Issue 9 pp 3836—3855

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

Kejie Huang1, *, , Lijuan Xu2, *, , Mingfang Jia2, , Wenmin Liu1, , Shijie Wang1, , Jianglong Han1, , Yanbo Li3, , Qibin Song1, , Zhenming Fu1, *, ,

  • 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • 2 Department of Health Management, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • 3 Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, China
* Equal contribution

Received: January 7, 2022       Accepted: April 25, 2022       Published: May 4, 2022
How to Cite

Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 (SIRHPV = 3.7, 95% CI: 2.9–4.6; SIRsmoking = 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 (Pinteraction < 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.


AP: attribution proportion due to interaction; CI: confidence intervals; EAR: excess absolute risk; HPV: human papillomavirus; HR: hazard ratio; S: synergy index; SPMs: second primary malignancies; SEER: Surveillance, Epidemiology, and End Results; SIR: standardized incidence ratio; RERI: relative excess risk due to interaction; RT: radiotherapy.