Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer

William C. Spanos, Paul Nowicki, Dong Wook Lee, Andrew Hoover, Bruce Hostager, Anjali Gupta, Mary E. Anderson, John H. Lee

Research output: Contribution to journalArticlepeer-review

180 Scopus citations


Background: Human papillomavirus (HPV) is the most identifiable cause of head and neck squamous cell cancer (HNSCC). Compared with HPV-negative HNSCC, HPV-positive HNSCC presents at an advanced stage but with significantly better survival. We created a syngeneic mouse model of HPV-positive and HPV-negative HNSCC by transforming mouse primary tonsil epithelial cells with either HPV oncogenes or a nonantigenic RNA interference strategy that affects similar oncogenic pathways. Objectives: To examine the effect of radiation therapy on HPV-positive and HPV-negative tumors in immunecompetent and immune-incompetent mice and to examine responses in human cancer cell lines. Design: Prospective in vivo murine model. Main Outcome Measures: Survival and tumor growth. Results: For human and murine transformed cell lines, HPV-positive cells were more resistant to radiation and cisplatin therapy compared with HPV-negative cells. In vivo, HPV-positive tumors were more sensitive to radiation, with complete clearance at 20 Gy, compared with their HPV-negative counterparts, which showed persistent growth. Cisplatin in vivo cleared HPV-positive tumors but not HPV-negative tumors. However, neither radiation or cisplatin therapy cured immune-incompetent mice. Adoptive transfer of wild-type immune cells into immune-incompetent mice restored HPV-positive tumor clearance with cisplatin therapy. Conclusions: The HPV-positive tumors are not more curable based on increased epithelial sensitivity to cisplatin or radiation therapy. Instead, radiation and cisplatin induce an immune response to this antigenic cancer. The implications of these results may lead to novel therapies that enhance tumor eradication for HPV-positive cancers.

Original languageEnglish (US)
Pages (from-to)1137-1146
Number of pages10
JournalArchives of Otolaryngology - Head and Neck Surgery
Issue number11
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology


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