Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer

Abstract

Human papilloma virus (HPV) infection has previously been reported to be associated with TP53 and TP16 expression in Japanese and Taiwanese patients with lung cancer, but data for advanced non-small cell lung cancer (NSCLC) patients is limited. The present study examined the association between HPV infection and TP53 and TP16 expression in Chinese patients with advanced NSCLC. HPV DNA was detected in 20 out of 83 (24%) lung tumors, and was observed more frequently in non-smokers, patients with lymph node metastasis, and patients with poorly differentiated tumors (P=0.048, P=0.044 and P=0.024, respectively). Thirteen (65%) out of 20 HPV-infected tumors were positive for TP53 expression while eight (40%) were positive for TP16 expression. Multivariate analysis revealed that poor differentiation alone (OR=0.163) was an independent predictive factor of HPV infection in NSCLC. TP16-positive patients had a significantly longer survival time when compared with TP16-negative patients (P<0.001, log-rank test), a trend a not observed for TP53. Our results suggest that TP53 and TP16 protein expression is not associated with the expression of HPV DNA, but that TP16 expression may be an independent prognostic factor of long survival in advanced NSCLC.

Human papillomavirus type 16 E6 oncoprotein promotes proliferation and invasion of non‐small cell lung cancer cells through Toll‐like receptor 3 signaling pathway

“…However, HPV16 E6 but not E7 oncoprotein induced extracellular regulated protein kinase (ERK) signaling pathway to enhance HIF‐1α accumulation . HPV E6 protein also bound cell cycle regulator TP53 to trigger degradation, promote proliferation, and inhibit apoptosis of NSCLC cells . Moreover, several studies revealed that Toll‐like receptors (TLRs) were involved in HPV‐induced squamous cell carcinoma, and higher expression of nucleic acid‐sensing TLRs predicted HPV16 clearance and associated with E6‐directed cell‐mediated response .…”