Robust Differences in p16-Dependent Oropharyngeal Squamous Cell Carcinoma Distant Metastasis: Implications for Targeted Therapy.
OBJECTIVE
Historically, head and neck squamous cell carcinoma (HNSCC) has been earmarked a lymphatic malignancy. Recently, this has been called into question. Our study aims to (1) illustrate the robust differences in distant metastases between p16+ and p16- oropharyngeal squamous cell carcinoma (OPSCC) and (2) provide support that p16+ OPSCC has a predilection toward vasculature invasion and hematogenous spread.


METHODS
Multi-institutional, case series with chart review.


METHODS
Four academic institutions.


METHODS
Within a group of 1113 patients with primary OPSCC who received treatment between 1979 and 2013, those who developed distant metastasis (DM) were divided into 2 cohorts based on p16 status. Intergroup and intragroup univariate analysis was performed as well as descriptive analysis of end-organ sites.


RESULTS
Of the 1058 patients included, 89 developed DM. Thirty were p16- and 59 were p16+. Of the p16- patients with DM, only 10% had disseminated disease (distant metastases at ≥2 sites) compared with 74% of p16+ patients. Distant disease in p16+ patients included brain, abdomen, and a distinct pattern of pulmonary metastases.


CONCLUSIONS
Our large, multi-institutional study supports published reports that p16+ OPSCC metastasizes with a unique phenotype that is hematogenous and widely disseminated with atypical end-organ sites. Our data suggest that p16+ OPSCC has a predilection toward active vasculature invasion as evidenced by the results and illustrative radiologic and pathohistologic examples. These findings may have implications for future targeted therapy when treating p16+ OPSCC.
Department of Otolaryngology-Head & Neck Surgery, Loyola University Medical Center, Maywood, Illinois, USA Head & Neck Medicinal Chemistry Laboratory, Edward Hines VA, Hines, Illinois, USA jamesjaber2@gmail.com.
James J
JJ
Jaber
Department of Otolaryngology-Head & Neck Surgery, Loyola University Medical Center, Maywood, Illinois, USA.
Lauren
L
Murrill
Department of Medicine, Division of Hematology & Oncology, Loyola University Medical Center, Maywood, Illinois, USA.
Joseph I
JI
Clark
Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Jonas T
JT
Johnson
Center for Neuropharmacology & Neuroscience, Albany Medical College, Albany, New York, USA.
Paul J
PJ
Feustel
Department of Otolaryngology-Head & Neck Surgery Louisiana State University Health Science Center, Shreveport, Louisiana, USA.
Vikas
V
Mehta
D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000821:virology; D012189:Retrospective Studies
distant metastasis; hematogenous spread; human papillomavirus; metastases; oropharyngeal squamous cell carcinoma; p16+; p16-dependent