A novel prediction model for human papillomavirus-associated oropharyngeal squamous cell carcinoma using p16 and subcellular β-catenin expression.
BACKGROUND
p16 overexpression is a highly sensitive yet moderately specific biomarker for predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Nuclear β-catenin translocation has been linked to HPV-positive OPSCC. However, whether the strategy of combining β-catenin with p16 can better predict HPV-associated OPSCC remains unknown.


METHODS
We evaluated the expression of p16 and β-catenin (nuclear and membrane) by immunohistochemistry staining in 101 OPSCC tissues and HPV status by HPV DNA in situ hybridization. Logistic regression models were used to evaluate single or multiple biomarkers for HPV prediction. The prediction power, sensitivity, and specificity were determined by receiver operating characteristic (ROC) analyses.


RESULTS
Our data showed that upon univariate analysis, p16 and nuclear β-catenin were positively correlated with HPV status, while membrane β-catenin was inversely correlated with HPV status (P < 0.01). p16 showed the highest HPV predictive power, with area under the curve (AUC) of 0.9074 compared to 0.6762 for nuclear β-catenin and 0.7635 for membrane β-catenin, respectively, indicating differential accuracies for HPV prediction. Multivariable analysis showed that p16 was significantly correlated with HPV, while nuclear and membrane β-catenin showed marginal significance. The three-biomarker model was similarly sensitive (98.9% vs. 100%) but more specific (88.9% vs. 81%) than p16 alone, which also showed a good predictive value for overall (P = 0.0002) survival and disease-free (P = 0.0158) survival.


CONCLUSIONS
Our study suggests a novel model of combining p16 and subcellular β-catenin for prediction of HPV-associatred OPSCC, and this finding deserves further validation.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Guoqing
G
Qian
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.|Department of Pathology, Xiangya Hospital, Xiangya Medical School, Central South University, Changsha, Hunan, China.
Zhongliang
Z
Hu
Ocean NanoTech, San Diego, CA, USA.
Hong
H
Xu
Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA, USA.
Susan
S
Müller
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Dongsheng
D
Wang
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Hongzheng
H
Zhang
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
Sungjin
S
Kim
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
Zhengjia
Z
Chen
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Nabil F
NF
Saba
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Dong M
DM
Shin
Ocean NanoTech, San Diego, CA, USA.
Andrew Y
AY
Wang
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Zhuo Georgia
ZG
Chen
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011237:Predictive Value of Tests; D000077195:Squamous Cell Carcinoma of Head and Neck; D051176:beta Catenin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; C495270:CTNNB1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D051176:beta Catenin
biomarker; head and neck cancer; human papillomavirus; model; p16; β-catenin