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Clinical Trial
. 2017 Jan;116(3):362-369.
doi: 10.1038/bjc.2016.434. Epub 2017 Jan 10.

Epithelial to mesenchymal transition and HPV infection in squamous cell oropharyngeal carcinomas: the papillophar study

Marine Lefevre  1 , Alexandra Rousseau  2 , Thomas Rayon  2 , Véronique Dalstein  3 , Christine Clavel  3 , Agnès Beby-Defaux  4 , Jean-Luc Pretet  5 , Patrick Soussan  6   7 , Myriam Polette  3 , Jean Lacau Saint Guily  8 , Philippe Birembaut  3 ; Papillophar Study Group
Collaborators, Affiliations
Clinical Trial

Epithelial to mesenchymal transition and HPV infection in squamous cell oropharyngeal carcinomas: the papillophar study

Marine Lefevre et al. Br J Cancer. 2017 Jan.

Abstract

Background: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas.

Methods: We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16INK4a expression and survival outcomes in a cohort of 296 patients with OPC.

Results: Among the 296 OPSSC, 26% were HPV positive, 20.3% had overt EMT (>25% of vimentin positive tumour cells). Lower E-cadherin expression was associated with a higher risk of distant metastasis in univariate (P=0.0110) and multivariate analyses (hazard ratios (HR)=6.86 (1.98; 23.84)). Vimentin expression tends towards worse metastasis-free survival (MFS; HR=2.53 (1.00; 6.41)) and was an independent prognostic factor of progression-free survival (HR=1.55 (1.03; 2.34)).

Conclusions: There was a non significant association of EMT with HPV status. This may be explained by a mixed subpopulation of patients HPV positive with associated risk factors (HPV, tobacco and alcohol). Thus, the detection of EMT in OPC represents another reliable approach in the prognosis and the management of OPC whatever their HPV status.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Expression of p16ink4a in tumour cells of OPC (A). Vimentin is expressed in tumour clusters at the invasion front (B) while E-cadherin (C) and β-catenin (D) are still present in tumour cell membranes in the same territory of an OPC (× 250).
Figure 2
Figure 2
(A) Kaplan–Meier estimation of MFS according to EMT level. (B) Kaplan–Meier estimation of PFS according to EMT level. (C) Kaplan–Meier estimation of MFS according to E-Cadherin expression. The full colour version of this figure is available at British Journal of Cancer online.
See this image and copyright information in PMC

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