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Neutrophils infiltration and its correlation with human papillomavirus status in the oral squamous cell carcinoma

Authors Li C, Zhao L, Wang Q, Ma S, Sun J, Ma C, Liu J, Jing X, Ai D, Nan Z, Qu X

Received 22 January 2019

Accepted for publication 6 April 2019

Published 5 June 2019 Volume 2019:11 Pages 5171—5185


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li

Chen Li,1,2 Lei Zhao,1 Qingjie Wang,1 Shao Ma,3 Jintang Sun,1 Chao Ma,1 Jia Liu,1 Xuanxuan Jing,1 Dan Ai,1 Zhaodi Nan,1 Xun Qu1

1Institute of Basic Medical Sciences, QiLu Hospital of Shandong University, Jinan 250012, Shandong, People’s Republic of China; 2Department of Radiation Oncology, QiLu Hospital of Shandong University, Jinan 250012, Shandong, People’s Republic of China; 3Department of Breast Surgery, QiLu Hospital of Shandong University, Jinan 250012, Shandong, People’s Republic of China

Purpose: One of the cardinal etiological factors for oral squamous cell carcinoma (OSCC) is Human papillomavirus (HPV). Neutrophils were potential targets of immune therapy for patients with OSCC. The objective of this study was to determine if neutrophils density and HPV status can be used to define a high-risk category of patients in OSCC and to investigate the possible relationship between them.
Patients and methods: We performed immunohistochemistry to probe neutrophils infiltration and HPV (P16) expression in 81 patients with OSCC. Prognostic factors for cancer-related survival were evaluated by univariate and multivariate analyses. We used the detection of cytokines to investigate the possible molecular mechanisms between neutrophils infiltration and HPV status.
Results: There were significantly higher numbers of CD15+ neutrophils infiltration in OSCC tissues. Higher numbers of CD15+ neutrophils infiltration was related to stage Ⅲ,Ⅳ (p<0.001), poor grade (p<0.001), lymph node metastasis (p=0.014), and the higher preoperative neutrophil-lymphocyte ratio (NLR) (p<0.001). HPV-negative status was also associated with stage Ⅲ,Ⅳ (p=0.001), poor grade (p=0.002), lymph node metastasis (p=0.005), radiotherapy (p=0.038), and the higher NLR (p=0.002). The high density of neutrophils was associated with worse cancer-related survival time (p<0.001) and was an independent prognostic factor for OSCC, while the HPV-positive group was associated with better cancer-related survival time. Moreover, high density of neutrophils was correlated with HPV-negative status in OSCC (p<0.001). Detection of cytokines and chemokines revealed that one of the chemotactic factors of neutrophils, IL-8, was exhibited relatively low expression by HPV-positive OSCC cells, whereas HPV-negative OSCC cells were found to drive an IL-8 secretion profile.
Conclusion: Neutrophils infiltration and HPV status appear to be prognostic parameters for OSCC. Overexpression of HPV18 E7 on OSCC cells may participate in depressing neutrophils infiltration to some extent through downregulating expression of IL-8.

Keywords: human papillomavirus, neutrophils, oral squamous cell carcinoma, IL-8

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