Expression of EGFR and HPV-associated p16 in oropharyngeal carcinoma: correlation and influence on prognosis after radiotherapy in the randomized DAHANCA 5 and 7 trials.
OBJECTIVE
EGFR and HPV-associated p16 are among the most investigated biomarkers in head and neck cancer. The aim was to investigate the correlation and interaction between these two markers and to evaluate their potential prognostic significance when combined.


METHODS
336 Oropharyngeal carcinomas treated with primary radiotherapy (66-68 Gy, 2fx/day, 10-12 Gy/week) and with known EGFR/p16-status estimated semiquantitatively by immunohistochemistry were included in the study. Data were evaluated by EGFR-expression (high/low) and p16-status (positive/negative) consequently dividing tumours into four groups by combination of the biomarkers. Patient/tumour characteristics and complete 5-year follow-up were available.


RESULTS
Low EGFR-expression was significantly more common in p16-positive tumours compared to p16-negative, p < 0.0001. p16 positivity showed a strong prognostic impact (p < 0.0001, HR = 0.22 [0.13-0.38]), whereas EGFR was a weak prognostic marker when local control was used as endpoint (p = 0.03, HR = 0.53 [0.29-0.94]). Combination of EGFR/p16 did not add significant information to p16 alone and by multivariable analysis only p16 showed significant prognostic information for all evaluated endpoints.


CONCLUSIONS
Both EGFR and p16 bear prognostic information in oropharyngeal cancer, although p16 is, by far, the strongest prognostic factor. The markers seem to be correlated and this might have influence when evaluating the effect of EGFR inhibition in oropharyngeal tumours.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Pernille
P
Lassen
Jens
J
Overgaard
Jesper Grau
JG
Eriksen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D066246:ErbB Receptors
EGFR; HNSCC; HPV; Radiotherapy; p16