Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial.
OBJECTIVE
To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial.


METHODS
Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction.


RESULTS
Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13).


CONCLUSIONS
HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.
Rischin
Danny
D
Department of Medical Oncology, Peter MacCallum Cancer Centre, A'Beckett St, Locked Bag No 1, Melbourne 8006, Australia. Danny.Rischin@petermac.org
Young
Richard J
RJ
Fisher
Richard
R
Fox
Stephen B
SB
Le
Quynh-Thu
QT
Peters
Lester J
LJ
Solomon
Ben
B
Choi
Jimin
J
O'Sullivan
Brian
B
Kenny
Lizbeth M
LM
McArthur
Grant A
GA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001315:Australia; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009367:Neoplasm Staging; D009520:New Zealand; D009656:North America; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D013020:South America; D013997:Time Factors; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin