Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection.
Medicine (Baltimore). 2015 Dec;94(50):e2187
Authors: Rhie A, Park WS, Choi MK, Kim JH, Ryu J, Ryu CH, Kim JI, Jung YS
Abstract
Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV-) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection.For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed.p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39-0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66-1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16 and p16- groups. A region containing PRDM2 was amplified only in the p16 group, whereas EGFR and 11q13.3 showed increased amplification in p16- counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16 OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS.p16 OSCC exhibit distinct CNV patterns compared with p16- counterpart. Specific patterns of CNVs predict better survival, especially in p16 OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV- OSCC.
PMID: 26683928 [PubMed - in process]
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