Use of gene expression signature to discriminate oropharyngeal cancers according to HPV16 status

• Published in: Journal of clinical oncology Vol. 31; no. 15_suppl; p. 6055
• Main Authors: Mirghani, Haitham, Ory, Catherine, Ugolin, Nicolas, Amen, Furrat, Guigay, Joel, Lacau Saint Guily, Jean, Chevillard, Sylvie, Lacave, Roger
• Format: Journal Article
• Language: English
• Published: 20.05.2013
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2013.31.15_suppl.6055

Abstract only 6055 Background: Strong evidence supports the hypothesis that high-risk human papillomavirus (HPV), particularly HPV16, is a causative agent for an increasing subset of oropharyngeal squamous cell carcinomas (OPSCC). These tumors have distinct oncogenic mechanisms and a more favorable prognosis than tobacco induced OPSCC. Although these differences emphasize the need for a specific therapeutic approach, HPV status is still not used to guide treatment. A better understanding of the molecular profile related to HPV16 induced OPSCC may help to develop personalized treatments. Methods: To identify an HPV16-related molecular signature, we compared the gene expression profile of 15 transcriptionally active HPV16-positive and 15 HPV16-negative OPSCC. The study was conducted in two steps. First, a learning set of 16 OPSCC comprising 8 HPV16-positives and 8 HPV16-negatives OPSCC was analyzed in order to identify the signature. Potentially confounding factors of stage, sex and tobacco consumption were equally distributed in both groups. Secondarily, the robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 14 OPSCC. Results: We identified a signature composed of 224 genes which discriminates HPV16-induced OPSCC from their tobacco induced counterparts. After the viral status was revealed, 13 out of 14 tumors were correctly classified according to tumor etiology, 1/14 was undetermined and none were misclassified. Interestingly, deregulated genes in HPV16-positive tumors are principally involved in innate immunity, in cell cycle regulation through the TP53/RB/E2F pathway, and autophagy through mTOR regulation. Well known targets of E6 and E7 proteins are also found to be deregulated. Conclusions: Our results demonstrate that a set of selected genes can distinguish OPSCC according to etiology. These genes shed light on HPV16 induced carcinogenesis since specific molecular pathways are deregulated. Further investigations are required for a better understanding of the differing natural histories and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HPV-related OPSCC.