title: Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection.
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.
authors.affiliation: From the Department of Biomedical Science, Department of Biochemistry and Molecular Biology, Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul (AR, J-IIK); Department of Pathology, Center for Specific Organs Cancer, Hematologic Malignancy Branch, National Cancer Center, Goyang, Gyeonggi (WSP, MKC); and Department of Otolaryngology-Head and Neck Surgery, Graduate School of Cancer Science and Policy, Specific Organs Cancer Branch, National Cancer Center, Goyang, Gyeonggi, Korea (J-HK, JR, CHR, Y-SJ).
authors.forename: Arang
authors.initials: A
authors.lastname: Rhie
authors.forename: Weon Seo
authors.initials: WS
authors.lastname: Park
authors.forename: Moon Kyung
authors.initials: MK
authors.lastname: Choi
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Junsun
authors.initials: J
authors.lastname: Ryu
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Ryu
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Yuh-Seog
authors.initials: YS
authors.lastname: Jung
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000502:physiology*; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D027383:Papillomaviridae / Q000302:isolation & purification; D011247:Pregnancy; D056910:Republic of Korea; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins