Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck.
OBJECTIVE
A subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16(INK4A) in these tumors. We evaluated p16(INK4A) as a prognostic marker of treatment response and survival in a well-defined and prospectively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial.


METHODS
Immunohistochemical expression of p16(INK4A) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone. The influence of p16(INK4A) status on locoregional tumor control, disease-specific survival, and overall survival after radiotherapy was evaluated.


RESULTS
p16(INK4A) positivity was found in 35 tumors (22%). Tumor-positivity for p16(INK4A) was significantly correlated with improved locoregional tumor control (5-year actuarial values 58% v 28%; P = .0005), improved disease-specific survival (72% v 34%; P = .0006), and improved overall survival (62% v 26%; P = .0003). In multivariate analysis, p16(INK4A) remained a strong independent prognostic factor for locoregional failure (hazard ratio [HR], 0.35; 95% CI, 0.19 to 0.64), disease-specific death (HR, 0.36; 95% CI, 0.20 to 0.64), and overall death (HR, 0.44; 95% CI, 0.28 to 0.68).


CONCLUSIONS
Expression of p16(INK4A) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy.
Lassen
Pernille
P
Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark. pernille@oncology.dk
Eriksen
Jesper G
JG
Hamilton-Dutoit
Stephen
S
Tramm
Trine
T
Alsner
Jan
J
Overgaard
Jens
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy* / Q000821:virology; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy* / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy* / Q000821:virology; D010919:Placebos; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010919:Placebos