Human papillomavirus and survival of patients with oropharyngeal cancer.
BACKGROUND
Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.


METHODS
We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer.


RESULTS
The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage.


CONCLUSIONS
Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)
University of Texas M.D. Anderson Cancer Center, Houston, USA.
K Kian
KK
Ang
Jonathan
J
Harris
Richard
R
Wheeler
Randal
R
Weber
David I
DI
Rosenthal
Phuc Felix
PF
Nguyen-Tân
William H
WH
Westra
Christine H
CH
Chung
Richard C
RC
Jordan
Charles
C
Lu
Harold
H
Kim
Rita
R
Axelrod
C Craig
CC
Silverman
Kevin P
KP
Redmond
Maura L
ML
Gillison
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000302:isolation & purification; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000821:virology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*