Human papillomavirus infection as a prognostic factor in oropharyngeal squamous cell carcinomas treated in a prospective phase II clinical trial.
The aim of this study was to determine the presence of high-risk HPV-16 in patients with HNSCC, assess the impact of HPV status on treatment response and survival in this select cohort treated with combined modality therapy and to identify the differences in HIF-1alpha and VEGF expression in HPV-positive and -negative tumors.


METHODS
Patients had resectable, untreated stage III, IV HNSCC of the oral cavity, oropharynx, hyopharynx or larynx, and stage II cancer of the base of tongue, hypopharynx and larynx. HPV status was determined by conventional PCR in fresh frozen biopsy samples and by Taqman PCR assay on formalin-fixed, paraffin-embedded specimens. HIF-1alpha and VEGF expression were assessed by quantitative real-time PCR (RT-PCR). Multivariate Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) based on HPV status.


RESULTS
HPV-16 was detected in 14 of 24 evaluable cases. There were no significant differences in response rates after neoadjuvant chemotherapy (86% vs. 90%) in HPV-positive and HPV-negative patients, respectively. There was a trend toward better progression-free (HR=0.15, 95% CI=0.002-12.54; p=0.06) and overall survival (HR=0.14, 95% CI=0.001-14.12; p=0.10) for HPV-positive patients. In a subset of 13 fresh frozen samples, RT-PCR revealed a significant increase in VEGF mRNA levels in HPV-positive tumors (p<0.01). No difference was seen for HIF-1alpha expression.


CONCLUSIONS
HPV presence portended a better prognosis in patients with oropharyngeal SCC treated with a multimodality treatment in a prospective clinical trial. The level of VEGF mRNA was up-regulated in HPV-16-positive tumors possibly through an HIF-1 independent manner.
Jo
Solomon
S
City of Hope National Medical Center, 1500 East Duarte Rd, Duarte, CA 91010, U.S.A.
Juhasz
Agnes
A
Zhang
Keqiang
K
Ruel
Christopher
C
Loera
Sofia
S
Wilczynski
Sharon P
SP
Yen
Yun
Y
Liu
Xiyong
X
Ellenhorn
Joshua
J
Lim
Dean
D
Paz
Benjamin
B
Somlo
George
G
Vora
Nayana
N
Shibata
Stephen
S
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy / Q000821:virology*; D003131:Combined Modality Therapy; D017931:DNA Primers; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology*; D011446:Prospective Studies; D016019:Survival Analysis
D017931:DNA Primers