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Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer.
Clin Cancer Res 2010; 16(7):2138-46CC

Abstract

PURPOSE

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.

EXPERIMENTAL DESIGN

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.

Authors+Show Affiliations

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Boston, MA 02114, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20233885

Citation

Nichols, Anthony C., et al. "Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome Following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 16, no. 7, 2010, pp. 2138-46.
Nichols AC, Finkelstein DM, Faquin WC, et al. Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Clin Cancer Res. 2010;16(7):2138-46.
Nichols, A. C., Finkelstein, D. M., Faquin, W. C., Westra, W. H., Mroz, E. A., Kneuertz, P., ... Rocco, J. W. (2010). Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 16(7), pp. 2138-46. doi:10.1158/1078-0432.CCR-09-3185.
Nichols AC, et al. Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome Following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer. Clin Cancer Res. 2010 Apr 1;16(7):2138-46. PubMed PMID: 20233885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. AU - Nichols,Anthony C, AU - Finkelstein,Dianne M, AU - Faquin,William C, AU - Westra,William H, AU - Mroz,Edmund A, AU - Kneuertz,Peter, AU - Begum,Shahnaz, AU - Michaud,William A, AU - Busse,Paul M, AU - Clark,John R, AU - Rocco,James W, Y1 - 2010/03/16/ PY - 2010/3/18/entrez PY - 2010/3/18/pubmed PY - 2010/8/7/medline SP - 2138 EP - 46 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 16 IS - 7 N2 - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/20233885/Bcl2_and_human_papilloma_virus_16_as_predictors_of_outcome_following_concurrent_chemoradiation_for_advanced_oropharyngeal_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=20233885 DB - PRIME DP - Unbound Medicine ER -