Significance of p16 expression in head and neck cancer patients treated with radiotherapy and cetuximab.
BACKGROUND
HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated.


METHODS
We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan-Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data.


RESULTS
Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6% positivity; 92% of all cases), while EGFR was expressed at high levels in all tumor subsites (82%). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80% in p16-positive vs. 33% overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival.


CONCLUSIONS
Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.
Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Gregor
G
Heiduschka
Anja
A
Grah
Felicitas
F
Oberndorfer
Rudolf
R
Seemann
Alexander
A
Kranz
Gabriela
G
Kornek
Fritz
F
Wrba
Dietmar
D
Thurnher
Edgar
E
Selzer
D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D066246:ErbB Receptors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*
D061067:Antibodies, Monoclonal, Humanized; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab