Expression of p16, p53, and TLR9 in HPV-Associated Head and Neck Squamous Cell Carcinoma: Clinicopathological Correlations and Potential Prognostic Significance
Authors Wang S, Zhuang X, Gao C, Qiao T
Received 24 November 2020
Accepted for publication 16 January 2021
Published 5 February 2021 Volume 2021:14 Pages 867—877
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Gaetano Romano
Shu Wang, Xibing Zhuang, Caixia Gao, Tiankui Qiao
Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, 201508, People’s Republic of China
Correspondence: Tiankui Qiao
Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Jinshan District, Shanghai, 201508, People’s Republic of China
Tel +86 189 3077 8786
Purpose: To investigate the association of human papillomavirus (HPV) status with p16, p53, and TLR9 expression in head and neck squamous cell carcinoma (HNSCC) and to evaluate these proteins as potential surrogate prognostic markers.
Methods: Expression of p16, p53, and TLR9 was assessed by immunohistochemistry, and HPV status was analyzed by in situ hybridization in 85 tumors of patients with HNSCC. Chi-square test was performed to evaluate the correlations of HPV infection with p16, p53, and TLR9 expression. Kaplan–Meier method and Cox regression analyses were applied to evaluate the associations between the expression levels of these proteins and patient outcomes.
Results: Overall, 24 of the 85 HNSCC specimens were associated with HPV infection. High expression of p16, p53, and TLR9 in tumor cells was observed in 31.76%, 61.18%, and 49.41% of the specimens, respectively. p16 showed a higher diagnostic odds ratio for the prediction of HPV DNA positivity than p53 and TLR9. Improved 5-year overall and disease-free survival correlated with HPV positivity and high p16, low p53, and low TLR9 expression. Associations with improved outcomes were also observed for marker combinations high p16/low p53 and high p16/low p53/low TLR9. In a multivariate analysis, the high p16/low p53 signature showed the lowest hazard ratio regarding death.
Conclusion: The expression of p16, p53, and TLR9 in HNSCC is associated with HPV status. High p53 and TLR9 expression may be related to poor outcomes. The two-marker signature high p16/low p53 in tumor cells is a reliable tool for patient survival prognostication in HNSCC.
Keywords: head and neck squamous cell carcinoma, human papillomavirus, p16, p53, TLR9, prognosis
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