Oropharyngeal squamous cell carcinoma (OSCC) presents heterogeneous clinical behavior and response to therapies. There is a need to improve the classification to better stratify patients and therapeutic options. HPV-positive OSCC subset is recognized to have generally a much more favorable prognosis. To the opposite, epithelial-to-mesenchymal transition (EMT), a key process associated with tumor progression and metastasis, is associated with poor prognosis. This process is known to increase treatment resistance in many cancers. It also could play a role in oropharyngeal carcinoma and could explain the clinical evolution.
The aim of this work was to characterize the EMT signature of HPV-positive and HPV-negative OSCC in a retrospective cohort.
A total of 40 patients diagnosed between 2004 and 2013 in the University Hospital of Reims and operated for OSCC were included in this study. Median age at diagnostic was 57 years [38-89]. FFPE specimens were evaluated for HPV status using HPV genotyping (Innolipa), E6E7 RT-qPCR, in situ hybridization for high-risk HPV-DNA and p16 immunohistochemistry. EMT marker expression was detected by immunohistochemistry, to evaluate expression loss of epithelial markers (E-cadherin and β-catenin) and expression gain of mesenchymal markers (vimentin and N-cadherin).
Ten OSCC cases (25 %) were found to be HPV-positive. Twenty-nine cases (72,5 %) harbored one or more EMT markers. This seems to be more frequent in HPV-negative group (80 %) than in HPV-positive group (50 %) but this association was not statistically significant (p=0,066). As expected, HPV status was associated with a better overall survival and relapse-free survival. In the opposite, EMT was associated with a worse overall survival and early relapse-free survival. This was also the case specifically in the HPV-negative group but could not be verified in the HPV-positive group, due to the small size of the group.
We draw the hypothesis that EMT and HPV status could be combined to define different prognostic outcomes: more favorable for EMT-/HPV+, less favorable for EMT+/HPV-. The understanding of the role of EMT in HPV-induced OSCC could help to select therapeutic options and particularly to properly select HPV-positive OSCC patients that could benefit from treatment de-intensification.