BACKGROUND: Given the extended survival of patients diagnosed with cervical 
cancer, the large number of these women treated with radiotherapy, and the 
presence in this population of established cancer risk factors such as human 
papillomavirus (HPV) infection and cigarette smoking, it is important to clarify 
long-term trends in second cancer risk.
METHODS: Using data from 104,760 one-year survivors of cervical cancer reported 
to 13 population-based cancer registries in Denmark, Finland, Norway, Sweden, 
and the United States, we calculated standardized incidence ratios (SIRs) for 
second cancers overall and cancers at particular sites among women with cervical 
cancer, including cervical cancer patients who were treated or not treated with 
radiation, over more than 40 years of follow-up. Cox regression models were used 
to assess the time-varying association of radiotherapy with risk of second 
cancers and to assess the interaction of radiation treatment with age at 
diagnosis. All statistical tests were two-sided.
RESULTS: Among 104,760 one-year survivors of cervical cancer, the risk of all 
second cancers taken together was increased to a statistically significant 
extent (n = 12,496; SIR = 1.30; 95% confidence interval [CI] = 1.28 to 1.33). 
Compared with the general population, in both radiotherapy (N = 52,613) and 
no-radiotherapy groups (N = 27,382), risks for HPV-related cancers (of the 
pharynx, genital sites, and rectum/anus) and smoking-related cancers (of the 
pharynx, trachea/bronchus/lung, pancreas, and urinary bladder) were elevated to 
a statistically significant extent. Cervical cancer patients treated with 
radiotherapy, but not those who did not receive radiotherapy, were at increased 
risk for all second cancers and cancers at heavily irradiated sites (colon, 
rectum/anus, urinary bladder, ovary, and genital sites) beyond 40 years of 
follow-up compared with women in the general population. The association of 
radiotherapy with second cancer risk was modified by age at cervical cancer 
diagnosis for rectum/anus, genital sites, and urinary bladder, with higher 
hazard ratios for second cancer at younger ages of cervical cancer. After 
adjustment for competing mortality, the 40-year cumulative risk of any second 
cancer was higher among women diagnosed with cervical cancer before age 50 
(22.2%; 95% CI = 21.5% to 22.8%) than among women diagnosed after age 50 (16.4%; 
95% CI = 16.1% to 16.9%).
CONCLUSION: Cervical cancer patients treated with radiotherapy are at increased 
risk of second cancers at sites in close proximity to the cervix beyond 40 years 
of follow-up.