Human Papillomavirus (HPV) infection, particularly HPV16, is now recognized as a major etiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPSSC). HPV-related OPSSC respond better to treatments and generally have a significantly favorable survival outcome. By contrast, epithelial to mesenchymal transition (EMT) implicated in tumor invasion, is a hallmark of a poor prognosis in numerous carcinomas.
Our objective was to study the relationship of EMT markers with HPV infection and survival outcomes in a prospective study of a cohort of 302 well clinically characterized patients with OPSSC.
EMT was investigated by the immunohistochemical detection of E-cadherin, beta-catenin and vimentin in OPSSC. Considering vimentin as the best marker of EMT, EMT was graded according to vimentin scoring expression as follows: 0 = no EMT for vimentin score from 0 to 10%, 1 = mild EMT for vimentin score between 11 and 25%, 2 = overt EMT for vimentin score above 25%.HPV infection was identified by DNA and oncogenic proteins E6/E7 mRNA detection and p16ink4a immunohistochemical expression.
Among the 302 OPSSC, 25.8% were HPV positive, 12% had mild EMT (and 20.6% overt EMT. In multivariate analysis, HPV positive patients had better loco-regional disease free survival (HR=0.290 [0.122; 0.692], p=0.0053), overall survival (HR=0.228 [0.109; 0.477], p <0.0001), event free survival (HR=0.431 [0.256; 0.724], p= 0.0015) than HPV negative patients (HR=0.431[0.256; 0.724], p=0.0015). EMT was an independent prognostic factor of metastasis free (overt EMT/no EMT: HR=1.750 [1.157; 2.644], p=0.008) and event-free survival (overt EMT/no EMT HR=3.773 [1.446; 9.845], p=0.0066).
There was a trend for, but non-significant association of EMT with HPV negative carcinomas. This may be explained by a mixed population with associated different risk factors (HPV, tobacco and alcohol), which may interfere in the tumorigenic pathways of these carcinomas.
The detection of EMT in OPSSC represents a reliable approach in the prognosis and eventually the treatment of these cancers whatever their HPV status.