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

Lookup NU author(s): Dr Max RobinsonORCiD


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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.

Publication metadata

Author(s): Dale OT, Aleksic T, Shah KA, Han C, Mehanna H, Rapozo DCM, Sheard JDH, Goodyear P, Upile NS, Robinson M, Jones TM, Winter S, Macaulay VM

Publication type: Article

Publication status: Published

Journal: Carcinogenesis

Year: 2015

Volume: 36

Issue: 6

Pages: 648-655

Print publication date: 01/06/2015

Online publication date: 20/04/2015

Acceptance date: 21/03/2015

ISSN (print): 0143-3334

ISSN (electronic): 1460-2180

Publisher: Oxford University Press


DOI: 10.1093/carcin/bgv053


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Funder referenceFunder name
British Association of Head and Neck Oncologists
National Institutes of Health Research
Oracle Cancer Trust
Oxford Biomedical Research Centre
Royal College of Surgeons of England
Heads Up
G2012/25Prostate Cancer UK