Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer.
OBJECTIVE
Oropharyngeal squamous cell carcinoma (OPSCC) associated with human papilloma virus (HPV) is rapidly growing in incidence. Despite better prognosis than OPSCC associated with traditional risk factors, treatment failure still occurs in a significant proportion of patients. We had identified the antiapoptotic protein Bcl2 as a marker for poor outcome in advanced OPSCC treated with concurrent chemoradiation. To determine whether Bcl2 and HPV together might further characterize treatment response, we examined whether the prognostic value of Bcl2 was independent of HPV status.


METHODS
Pretreatment tumor biopsies from 68 OPSCC patients were tested for HPV by in situ hybridization and were immunostained for Bcl2 to evaluate relations with disease-free (DFS) and overall survival following platin-based concurrent chemoradiation. Median follow-up among surviving patients was 47 months (range, 10-131 months).


RESULTS
Bcl2 and HPV independently predicted DFS and overall survival. Hazard ratios (with 95% confidence interval) for positive versus negative status in bivariate Cox proportional hazard analysis of DFS were 6.1 (1.8-21) for Bcl2 and 0.11 (0.035-0.37) for HPV. Only 1 of 32 HPV-positive/Bcl2-negative tumors recurred. Pretreatment Bcl2 expression was specifically associated with distant metastasis; five of six distant metastases occurred in the <40% of patients whose primary tumors were Bcl2 positive.


CONCLUSIONS
Independent of HPV status, pretreatment Bcl2 expression identifies a subset of OPSCC patients having increased risk of treatment failure, particularly through distant metastasis, after concurrent chemoradiation. Considering HPV and Bcl2 together should help in devising better personalized treatments for OPSCC.
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Boston, MA 02114, USA.
Anthony C
AC
Nichols
Dianne M
DM
Finkelstein
William C
WC
Faquin
William H
WH
Westra
Edmund A
EA
Mroz
Peter
P
Kneuertz
Shahnaz
S
Begum
William A
WA
Michaud
Paul M
PM
Busse
John R
JR
Clark
James W
JW
Rocco
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000821:virology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D011878:Radiotherapy; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019253:Proto-Oncogene Proteins c-bcl-2