Human papillomavirus and survival of patients with oropharyngeal cancer

K. Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I. Rosenthal, Phuc Felix Nguyen-Tân, William H. Westra, Christine H. Chung, Richard C. Jordan, Charles Lu, Harold Kim, Rita Axelrod, C. Craig Silverman, Kevin P. Redmond, Maura L. Gillison

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated- fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. RESULTS: The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P = 0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional packyear of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. CONCLUSIONS: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.).

Original languageEnglish (US)
Pages (from-to)24-35
Number of pages12
JournalNew England Journal of Medicine
Volume363
Issue number1
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Medicine(all)

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    Ang, K. K., Harris, J., Wheeler, R., Weber, R., Rosenthal, D. I., Nguyen-Tân, P. F., Westra, W. H., Chung, C. H., Jordan, R. C., Lu, C., Kim, H., Axelrod, R., Silverman, C. C., Redmond, K. P., & Gillison, M. L. (2010). Human papillomavirus and survival of patients with oropharyngeal cancer. New England Journal of Medicine, 363(1), 24-35. https://doi.org/10.1056/NEJMoa0912217