Journal of the National Cancer Institute Advance Access originally published online on October 30, 2007
JNCI Journal of the National Cancer Institute 2007 99(21):1634-1643; doi:10.1093/jnci/djm201
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Published by Oxford University Press 2007.
ARTICLES |
Second Cancers Among 104760 Survivors of Cervical Cancer: Evaluation of Long-Term Risk
Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (AKC, EAE, ESG, BEC, RAK, LBT); Danish Cancer Society, Copenhagen, Denmark (HS, MA); The University of Iowa, Iowa City, IA (CFL); Karolinska Institutet, Stockholm, Sweden (PH, MK); Cancer Registry of Norway, Oslo, Norway (FL, SDF); Finnish Cancer Registry, Helsinki, Finland (EP); Helsinki University Central Hospital, Helsinki, Finland (HJ); International Epidemiology Institute, Rockville, MD (JDB); Vanderbilt-Ingram Cancer Center, Nashville, TN (JDB); Exponent Inc, New York, NY (LBT)
Correspondence to: Anil K. Chaturvedi, PhD, Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd, EPS 7072, Rockville, MD 20852 (e-mail: chaturva{at}mail.nih.gov).
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 104760 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 104760 one-year survivors of cervical cancer, the risk of all second cancers taken together was increased to a statistically significant extent (n = 12496; SIR = 1.30; 95% confidence interval [CI] = 1.28 to 1.33). Compared with the general population, in both radiotherapy (N = 52613) and no-radiotherapy groups (N = 27382), 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.
| CONTEXT AND CAVEATS Prior knowledge Previous studies have indicated that the risk of second cancers is increased among cervical cancer survivors, but overall and site-specific risks among very long-term survivors were unclear. Study design The authors used cancer registry data to compare the incidence of cancer in cervical cancer survivors with that of the general population. Regression models were used to determine the association of potential risk factors among these survivors with the incidence of second cancers overall and of particular second cancers. Contribution The risk of second cancers at sites that receive high doses of radiation during the treatment of cervical cancer increased with time, and the increase extended beyond 40 years after treatment. Implications The findings of this study may be useful in optimizing screening for second cancers among cervical cancer survivors. Limitations The multiple statistical comparisons conducted may have led to false-positive associations between the incidence of particular cancers and certain potential risk factors.
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Manuscript received December 8, 2006; revised July 26, 2007; accepted September 24, 2007.
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J Natl Cancer Inst 2008 100: 600.
J Natl Cancer Inst 2007 99: 1561.
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