p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters.
BACKGROUND
Currently, staging of head neck squamous cell carcinoma (HNSCC) is on the basis of primary tumor extension (cT), lymph node involvement (cN) and distant metastasis (cM). The aim of cancer staging was to improve diagnosis, prognosis and to compare outcome results. A new subgroup of oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV) infection is reported to show an increasing incidence. These HPV-positive OPSCC show distinct molecular differences, specific p16 overexpression and a significantly better prognosis. Therefore, the aim of this study was to evaluate the prognostic influence of p16 expression in OPSCC and compare its relevance with the established prognostic markers cT and cN classification and the clinical stages I-IV.


METHODS
Immunohistochemistry for p16 was carried out on the basis of a tissue microarray including 102 OPSCC patients with corresponding retrospective clinicopathological and follow-up data.


RESULTS
p16 is the strongest independent prognostic marker in OPSCC, surpassing the significance of cT and cN classification as well as the clinical stages I-IV. Prognosis of p16-positive OPSCC of an advanced stage reached or even exceeded prognosis of the next clinically smaller conventionally staged group of tumors.


CONCLUSIONS
p16 is the most relevant prognostic marker in OPSCC and should be considered for inclusion into the official staging system of HNSCC.
Fischer
C A
CA
Departments of Otolaryngology, Head and Neck Surgery. Electronic address: cfischer@uhbs.ch.
Kampmann
M
M
Departments of Otolaryngology, Head and Neck Surgery.
Zlobec
I
I
Departments of Pathology, University Hospital, Basel, Switzerland.
Green
E
E
Departments of Otolaryngology, Head and Neck Surgery.
Tornillo
L
L
Departments of Pathology, University Hospital, Basel, Switzerland.
Lugli
A
A
Departments of Pathology, University Hospital, Basel, Switzerland.
Wolfensberger
M
M
Departments of Otolaryngology, Head and Neck Surgery.
Terracciano
L M
LM
Departments of Pathology, University Hospital, Basel, Switzerland.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins