p16 cutoff in head and neck squamous cell carcinoma: correlation between tumor and patient characteristics and outcome.
BACKGROUND
p16 has been indicated as a suitable surrogate biomarker of HPV infection. The prognosis of p16-positive oropharynx tumors (OTs) of squamous cell carcinoma (SCC) histology is better than that of p16-negative tumors.


METHODS
We analyzed 209 samples of head and neck SCC to establish a predictive cutoff for p16 and determine the role of p16 positivity in OTs versus non-OTs. We compared the outcomes of tumors harboring any percentage of p16-positive cells (≥1%) with those of p16-negative OTs. We then considered 3 cutoffs (10%, 50% and 70% positive cells) to evaluate the outcome of OTs/non-OTs with similar p16 expression and p16-positive versus p16-negative tumors stratified by patient age.


RESULTS
p16-negative tumors among OTs and non-OTs were 29% and 49%, respectively (p = 0.0054). The cumulative distribution showed that the positive values were located around 2 focus points: 2% and 96%. Subgroup analysis showed that only OTs occurred in young patients (aged &lt;65 years) and that there was a ≥70% gain in survival in cases with p16-positive cells.


CONCLUSIONS
p16 positivity influences outcome only in young patients and OTs (p = 0.048).
Medical Oncology Unit, Department of Clinical Oncology, S. Croce University Hospital, Cuneo - Italy.
Marco Carlo
MC
Merlano
Medical Oncology Unit, Department of Clinical Oncology, S. Croce University Hospital, Cuneo - Italy.
Nerina
N
Denaro
Laboratory of Cancer Genetics and Translational Oncology, Department of Clinical Oncology, S. Croce University Hospital, Cuneo - Italy.
Daniela
D
Vivenza
Laboratory of Cancer Genetics and Translational Oncology, Department of Clinical Oncology, S. Croce University Hospital, Cuneo - Italy.
Martino
M
Monteverde
Department of Radiation Oncology, S. Croce University Hospital, Cuneo - Italy.
Elvio
E
Russi
Department of Otolaryngology, S. Croce University Hospital, Cuneo - Italy.
Walter
W
Lerda
Department of Histopathology, S. Croce University Hospital, Cuneo - Italy.
Alberto
A
Comino
Laboratory of Cancer Genetics and Translational Oncology, Department of Clinical Oncology, S. Croce University Hospital, Cuneo - Italy.
Cristiana
C
Lo Nigro
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D011379:Prognosis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors