Abstract 3550: Differences in immune escape in HPV+ versus HPV- head and neck squamous cell carcinoma
Authors: Russell Sarah M. , Lechner Melissa G. , Angell Trevor E. , Correa Adrian J. , Epstein Alan L. 
Published: August 2012

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and has not seen an improvement in survival in decades. Current standard-of-care treatments including surgical resection, chemotherapy and radiation still lead to high rates of recurrence and loco-regional metastasis contributing to the poor prognosis in these patients. It is well established that HNSCC are highly immune-modulatory tumors and may therefore benefit from immunotherapy treatment regimens. Better methods are therefore needed to match patients with the appropriate immunotherapy. Recently, human papillomavirus (HPV) was implicated in the etiology of a subset of HNSCC arising in younger patients without a history of alcohol and tobacco use. Approximately 30% of HNSCC tumors are HPV+ and despite late stage presentation, often have a better prognosis and response to therapy. This study examines how host immune recognition and response varies between HPV+ and HPV- HNSCC, with the goal of identifying new targets for immunotherapy. The immune profile and HPV infection status of 41 HNSCC patient tumor samples obtained from surgical resection was characterized by qRT-PCR, PCR, and IHC techniques. Tumor samples were analyzed for the expression of 40 genes involved in immune activation and suppression in the tumor microenvironment to generate an immune profile. Gene expression levels were normalized to GAPDH and compared across HPV+, HPV- and normal tissue groups by ANOVA and post-test pairwise analysis. HPV infectivity of tumor biopsies was determined using HPV consensus primers (MY09/MY11 and GP5+/GP6+) and confirmed with p16 immunohistochemistry. From these studies, eight of 41 (20%) HNSCC biopsies were HPV+ by PCR and IHC analysis. HPV+ tumors demonstrated statistically significant increased expression of genes related to immunosuppression including regulatory T (CD4, FoxP3, CTLA-4, and FasL) and myeloid suppressor cell markers (CD11b and IL-6, an inducer of these suppressor cells), as well as negative-regulators (SOCS1) (p&lt;0.05). These tumors also demonstrated an increase in markers of immune activation and infiltration, including evidence of T cells (CD4, Fas-L), antigen presenting cells (CD80, CD83, CD1c), and inflammatory cytokines and co-stimulatory molecules (IL-2, IL-12, IFN- γ, and OX40L) (p&lt;0.05). There were no statistically significant differences in gene expression found between normal tissue and HPV- HNSCC tumors. These studies demonstrate a general pattern of increased immunogenicity and concurrent immunosuppression in patients with HPV+ versus HPV- HNSCC that could potentially be used to inform immunotherapy treatment of HNSCC patients. HPV+ tumors may be more effectively treated with a regimen that employs a combination of immune stimulation and reversal of immune tolerance mechanisms, while HPV- tumors may require greater immune stimulation to activate endogenous anti-tumor immune responses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3550. doi:1538-7445.AM2012-3550