IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer

Oliver T Dale, Tamara Aleksic, Ketan A Shah, Cheng Han, Hisham Mehanna, Davy C M Rapozo, Jon D H Sheard, Paul Goodyear, Navdeep S Upile, Max Robinson, Terence M Jones, Stuart Winter, Valentine M Macaulay

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.

Original languageEnglish
Pages (from-to)648-55
Number of pages8
JournalCarcinogenesis
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 2015

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell
  • Cell Transformation, Neoplastic
  • Combined Modality Therapy
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Head and Neck Neoplasms
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Papillomaviridae
  • Papillomavirus Infections
  • Receptor, IGF Type 1
  • Young Adult

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