Subsequent malignant neoplasms in the Childhood Cancer Survivor Study: Occurrence of cancer types in which human papillomavirus is an established etiologic risk factor

Tara O. Henderson, Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, Illinois.
Brynn W. Fowler, Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, Illinois.
Haley A. Hamann, Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, Illinois.
Paul C. Nathan, Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jillian Whitton, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Kevin C. Oeffinger, Duke Cancer Institute, Duke University, Durham, North Carolina.
Joseph P. Neglia, Pediatric Hematology, Oncology, Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
Lucie M. Turcotte, Pediatric Hematology, Oncology, Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
Michael A. Arnold, Department of Pathology, Children's Hospital of Colorado, University of Colorado, Denver, Colorado.
Miriam R. Conces, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Rebecca M. Howell, Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Leslie L. Robison, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee.
Gregory T. Armstrong, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee.Follow
Kenneth A. Alexander, Pediatric Infectious Diseases, Nemours Children's Hospital, Orlando, Florida.

Abstract

BACKGROUND: Human papillomavirus (HPV)-associated subsequent malignant neoplasms (SMN ) in childhood cancer survivors are poorly understood. METHODS: The cumulative risk of SMN was assessed among 24,363 Childhood Cancer Survivor Study participants. Standardized incidence ratios (SIRs) and absolute excess risk were calculated using age-matched, sex-matched, and calendar year rates from the Surveillance, Epidemiology, and End Results program. Poisson regression models identified SMN risk factors, evaluating relative SIRs (rSIR) and 95% confidence intervals (95% CIs). RESULTS: In total, 46 survivors developed an SMN (median age, 31 years [range, 10-56 years]; median time from primary cancer, 21 years [range, 9-35 years]). SMN sites included oropharynx (N = 44), anorectum (N = 6), uterine cervix (N = 2), and vulva (N = 2). The 33-year cumulative incidence was 0.3% (95% CI, 0.2%-0.4%), and the SIR was nearly 3-fold that of the general population (SIR, 2.86; 95% CI, 2.05-4.00). Female survivors were not at increased risk of cervical or vulvar cancers compared with the general population. All survivors had an elevated risk of oropharyngeal SMN (males: SIR, 4.06; 95% CI, 2.37-6.97; females: SIR, 8.44; 95% CI 4.88-14.61) and anorectal SMN (males: SIR, 13.56; 95% CI, 5.09-36.13; females: SIR, 9.15; 95% CI, 2.29-36.61). Males (vs females: rSIR, 1.99; 95% CI, 1.00-3.94); head, neck, and pelvic radiotherapy doses >3000 centigray (vs none: rSIR, 2.35; 95% CI, 1.11-4.97); and cisplatin-equivalent doses >400 mg/m (vs none: rSIR, 4.51; 95% CI, 1.78-11.43) were associated with increased SMN SIRs in multivariable analysis. CONCLUSIONS: Childhood cancer survivors are at increased risk for SMN in sites susceptible to HPV-associated malignancies. Further research examining HPV in the etiology of SMN and the promotion of HPV vaccination and surveillance guidelines for SMN in cancer survivors is warranted.

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Cancer

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