Dataset Information

DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma.

ABSTRACT: Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes, and comprise two biologically and clinically distinct diseases. While OPSCC that arise from human papillomavirus infections (HPV+) have better overall survival than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing dramatically, affecting younger individuals which are often left with life-long co-morbidities from aggressive treatment. To identify patients which do poorly versus those who might benefit from milder regimens, risk-stratifying biomarkers are now needed within this population. One potential marker is the DEK oncoprotein, whose transcriptional upregulation in most malignancies is associated with chemotherapy resistance, advanced tumor stage, and worse outcomes. Herein, a retrospective case study was performed on DEK protein expression in therapy-naïve surgical resections from 194 OPSCC patients. We found that DEK was associated with advanced tumor stage, increased hazard of death, and interleukin IL6 expression in HPV16+ disease. Surprisingly, DEK levels in HPV16- OPSCC were not associated with advanced tumor stage or increased hazard of death. Overall, these findings mark HPV16- OPSCC as an exceptional malignancy were DEK expression does not correlate with outcome, and support the potential prognostic utility of DEK to identify aggressive HPV16+ disease.

SUBMITTER: Smith EA

PROVIDER: S-EPMC5410314 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma.

Smith Eric A EA Kumar Bhavna B Komurov Kakajan K Smith Stephen M SM Brown Nicole V NV Zhao Songzhu S Kumar Pawan P Teknos Theodoros N TN Wells Susanne I SI

Oncotarget 20170401 14

Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes, and comprise two biologically and clinically distinct diseases. While OPSCC that arise from human papillomavirus infections (HPV+) have better overall survival than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing dramatically, affecting younger individuals which are often left with life-long co-morbidities from aggressive treatment. To identify patients which do poorly versus those who might benefit ...[more]

PMID: 28423581

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Project description:BackgroundThe revised 8th Edition American Joint Committee on Cancer (AJCC) Head and Neck Staging Manual distinguishes HPV-mediated from non-HPV-mediated oropharyngeal cancer (OpSCC). The objective was to analyze OpSCC treatment modalities and outcomes.MethodsA retrospective study of OpSCC patients treated with radiotherapy or chemoradiotherapy between January 1st, 2000, and December 31st, 2008, as identified from the BC Cancer Registry. All patients received treatment at cancer clinics and had at least 5 years follow-up post-treatment. A total of 1259 OpSCC patients were identified. After initial chart reviews, 288 patients were excluded from further analysis and the majority (n = 198) was due to not receiving curative treatment. Based on the availability of formalin-fixed, paraffin-embedded (FFPE) tissue, patients were divided into two cohorts: Study Cohort (FFPE available, n = 244) and General Cohort (FFPE unavailable, n = 727). The Study Cohort was restaged according to AJCC 8th Edition based on p16 immunohistochemistry status. Kaplan-Meier analysis was used to estimate the 5-year overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival (LFS).ResultsAmong 971 patients, OpSCC age-adjusted incidence rate was observed to have increased from 2.1 to 3.5 per 100,000 between 2000 and 2008. The General Cohort was relatively older than the Study Cohort (60.1 ± 10.5 vs. 57.3 ± 9.4), but both cohorts were predominantly males (78.3% vs. 76.2%). Amongst the Study Cohort, 77.5% were p16-positive, of whom 98.4% were down staged in the 8th Edition. These early-stage patients showed OS improvement for those treated with chemoradiation, compared to radiation alone (85.8% vs. 73.1%, p = 0.05).ConclusionsOpSCC incidence is increasing in BC. The addition of chemotherapy to radiotherapy may portend a benefit in OS even for early-stage p16-positive OpSCC. Additional research is necessary to assess the safety of treatment de-escalation even among early-stage disease.

Dataset Information

DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma.

Publications

DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma.

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