Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: An analysis of Eastern Cooperative Oncology Group trials

Athanassios Argiris, S. Li, M. Ghebremichael, A. M. Egloff, L. Wang, A. A. Forastiere, B. Burtness, R. Mehra

Research output: Contribution to journalArticle


Background: The purpose of this article was to study the association of human papillomavirus (HPV) with clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: Archival baseline tumor specimens were obtained from patients treated on two clinical trials in recurrent or metastatic SCCHN: E1395, a phase III trial of cisplatin and paclitaxel versus cisplatin and 5-fluorouracil, and E3301, a phase II trial of irinotecan and docetaxel. HPV DNAwas detected by in situ hybridization (ISH) with a wide-spectrum probe. p16 status was evaluated by immunohistochemistry. Clinical outcomes of interest were objective response, progression-free survival (PFS) and overall survival (OS). Results: We analyzed 64 patients for HPV ISH and 65 for p16. Eleven tumors (17%) were HPV+, 12 (18%) were p16+, whereas 52 (80%) were both HPV- and p16-. The objective response rate was 55% for HPV-positive versus 19% for HPV-negative (P = 0.022), and 50% for p16-positive versus 19% for p16-negative (P = 0.057). The median survival was 12.9 versus 6.7 months for HPV-positive versus HPV-negative patients (P = 0.014), and 11.9 versus 6.7 months for p16- positive versus p16-negative patients (P = 0.027). After adjusting for other covariates, hazard ratio for OS was 2.69 (P = 0.048) and 2.17 (P = 0.10), favoring HPV-positive and p16-positive patients, respectively. The other unfavorable risk factor for OS was loss of ≥5% weight in previous 6 months (P = 0.0021 and 0.023 for HPV and p16 models, respectively). Conclusion: HPV is a favorable prognostic factor in recurrent or metastatic SCCHN that should be considered in the design of clinical trials in this setting.

Original languageEnglish (US)
Article numbermdu167
Pages (from-to)1410-1416
Number of pages7
JournalAnnals of Oncology
Issue number7
StatePublished - Jul 2014



  • Head and neck cancer
  • Human papillomavirus

ASJC Scopus subject areas

  • Hematology
  • Oncology

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