Prognostic Significance of p16 Cellular Localization in Oropharyngeal Squamous Cell Carcinoma.
OBJECTIVE
p16 immunohistochemical expression serves as a surrogate for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). While HPV-positive OPSCC commonly demonstrates prominent nuclear expression, aberrant cytoplasmic expression has been demonstrated in tobacco-related head and neck cancers. The purpose of this study is to investigate the prognostic significance of p16 cellular localization in OPSCC.


METHODS
Retrospective cohort study and immunohistochemical expression analysis of 159 OPSCC patients treated at a tertiary-care Veterans Affairs Medical Center.


RESULTS
All patients included in this study were male and the majority had significant tobacco (91%) and alcohol (88%) exposure. Overall, 57% of tumors were p16-positive, 32 (20%) subjects have tumors demonstrating low nuclear/low cytoplasmic (LN/LC) p16 expression, 29 (18%) high nuclear/high cytoplasmic (HN/HC) expression, 25 (16%) high nuclear/low cytoplasmic (HN/LC) expression, and 5 (3%) low nuclear/high cytoplasmic (LN/HC) expression. The 5-year disease-free survival (DFS) for the p16-negative group was 13.7%, compared to p16-positive LN/LC 28.4%, LN/HC 0%, HN/LC 74.7%, and HN/HC 93.1% (p<0.0001). Overall survival for the p16-negative group was 24.2%, compared to p16-positive LN/LC 23.5%, LN/HC 0%, HN/LC 74.2%, and HN/HC 88.7% (p<0.0001). On multivariable analysis, HN/HC and HN/LC expression patterns were associated with a statistically significant decreased risk of recurrence and death compared to p16-negative tumors.


CONCLUSIONS
P16 localization has prognostic significance in OPSCC, with high nuclear expression associated with significantly better oncologic outcomes compared to low nuclear expression with high or low cytoplasmic p16 expression. P16 localization may provide additional insight into OPSCC carcinogenesis, particularly in patients with heavy tobacco exposure.
Department of Pathology, Michael E. DeBakey VA Medical Center, Houston, TX, USA Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Syeling
S
Lai
Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Ashley E
AE
Wenaas
Department of Head and Neck Surgery, The University of Texas, M.D. Anderson Cancer Center, TX, USA.
Vlad C
VC
Sandulache
Houston VA Health Services Research and Development Center, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Christine
C
Hartman
Houston VA Health Services Research and Development Center, Michael E. DeBakey VA Medical Center, Houston, TX, USA Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Elizabeth
E
Chiao
Houston VA Health Services Research and Development Center, Michael E. DeBakey VA Medical Center, Houston, TX, USA Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Jennifer
J
Kramer
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA jose_zevallos@med.unc.edu.
Jose P
JP
Zevallos
D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D021381:Protein Transport; D012307:Risk Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16
cellular localization; oropharyngeal cancer; p16; smoking; veteran