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      Association of p16 as Prognostic Factors for Oropharyngeal Cancer: Evaluation of p16 in 1470 Patients for a 16 Year Study in Northeast China

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          Abstract

          Human papillomavirus (HPV) is an etiological risk factor for oropharyngeal squamous cell carcinomas (OPSCC). Our study investigates the prevalence, prognostic, and clinicopathologic features of HPV-related oropharyngeal cancer in Northeast China and elucidates the involvement of p16 in the tumorigenesis and progression of OPSCC. Specimens from 1470 OPSCC patients collected from 2000 to 2016 were analyzed using the status of HPV by polymerase chain reaction (PCR) and p16 immunohistochemistry. Overexpression of p16 was observed in 81 (5.51%) of the 1470 cases, and HPV positive was present in 78 cases (5.31%) of the 1470 cases. HPV positive and p16 overexpression have a good concordance. However, we found that the etiological fraction of HPV in cancers of the OPSCCs was obviously lower in Northeast China than other cohorts previously reported. Interestingly, nearly 89% of patients with p16 expression were smokers, and nearly 70% of patients with p16 expression had a history of alcohol. Our study also demonstrates that p16 expression is significantly associated with early stage primary OPSCCs and the patients with p16 expression tend to show better survival following surgery and radiotherapy.

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          Most cited references19

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          Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial.

          To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.
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            Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas.

            To refine stage and prognostic group for human papillomavirus (HPV) -related nonmetastatic (M0) oropharyngeal cancer (OPC).
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              Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus-driven oropharyngeal cancer and are associated with recurrence.

              Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus-driven oropharyngeal cancer (HPV-OPC).
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                17 September 2018
                : 2018
                : 9594568
                Affiliations
                1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China
                2Department of Otolaryngology, Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
                3Department of Pathology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
                4Department of pathology, Harbin Medical University, Harbin, China
                5Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, China
                6Department of Microbiology, Harbin Medical University, Harbin, China
                7Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China
                Author notes

                Academic Editor: Tao Huang

                Author information
                http://orcid.org/0000-0002-8258-9175
                http://orcid.org/0000-0003-1395-4682
                Article
                10.1155/2018/9594568
                6166388
                30310820
                3c22af6c-6f12-4a7a-861c-3bf30b1146ad
                Copyright © 2018 Hong-xue Meng et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 November 2017
                : 22 December 2017
                : 23 January 2018
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81600539
                Award ID: 81372785
                Award ID: 81400443
                Award ID: 81372178
                Funded by: Natural Science Foundation of Heilongjiang Province
                Award ID: QC2012C041
                Award ID: LC2016038
                Funded by: Natural Science Foundation of Heilongjiang Province
                Award ID: ZHY16-032
                Funded by: Chinese Postdoctoral Science Foundation
                Award ID: 2015M581472
                Award ID: 2016T90310
                Funded by: Heilongjiang Provincial Postdoctoral Science Foundation
                Award ID: LBH-Z16101
                Award ID: LBH-TZ0616
                Funded by: Heilongjiang Human Resources and Social Security Bureau
                Funded by: Harbin Special Fund Project for Science and Technology Innovation
                Award ID: 2016RAQXJ203
                Funded by: Harbin Medical University Cancer Hospital
                Award ID: JY2016-06
                Categories
                Research Article

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