HPV disrupt the cytoskeleton in oral squamous cell carcinomas from non-oropharyngeal sites via the E-cadherin/Mena/SMA pathway.

In this paper, we aimed to evaluate the mechanism of actin cytoskeleton disruption, in oral squamous cell carcinoma (OSCC). A total of 43 patients with surgically resected OSCCs located in non-oropharyngeal regions were randomly selected. The expression of E-cadherin, β-catenin, smooth muscle actin (SMA), Mena, maspin, V-set and immunoglobulin domain containing 1 (VSIG1), β human chorionic gonadotropin (βhCG), and angiotensin-converting enzyme (ACE) was assessed via immunohistochemistry (IHC) and evaluated in association with the prevalence of high-risk human papillomavirus (HPV). Mena positivity (n = 30; 69.77%) was more frequent in poorly differentiated OSCC of the tongue and lips with high-risk HPV viral DNA and a lymph node ratio (LNR) ≤ 2.5. Loss of E-cadherin was more prevalent among poorly differentiated stage pT4N1 tumors with an LNR ≤ 2.5 and perineural invasion. These cases were classified as SMA-high tumors. Independent negative prognostic factors included high Mena expression, loss of E-cadherin, high SMA expression, and the presence of high-risk HPV. No VSIG1 positivity was observed. In conclusion, in non-oropharyngeal OSCC, cytoskeleton activity might be driven by the Mena/E-cadherin/SMA axis, reflecting active epithelial-mesenchymal interaction. High Mena intensity is an indicator of poorly differentiated carcinomas with high-risk HPV and unfavorable prognosis.