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Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis.
J Clin Oncol. 2006 Feb 10; 24(5):736-47.JC

Abstract

PURPOSE

We sought to determine the prevalence of biologically relevant human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC). Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis.

METHODS

Using real-time polymerase chain reaction for HPV16, we determined HPV16 viral load in a cohort of 79 OSCCs annotated with long-term patient follow-up. A tissue microarray including these cases was also analyzed for p53, p16, and Rb utilizing in situ quantitative protein expression analysis. Seventy-seven tumors were classified into a three-class model on the basis of p16 expression and HPV-DNA presence: class I, HPV-, p16 low; class II, HPV+, p16 low; and class III, HPV+, p16 high.

RESULTS

Sixty-one percent of OSCCs were HPV16+; HPV status alone was of no prognostic value for local recurrence and was barely significant for survival times. Overall survival was improved in class III (79%) compared with the other two classes (20% and 18%; P = .0095). Disease-free survival for the same class was 75% versus 15% and 13% (P = .0025). The 5-year local recurrence was 14% in class III versus 45% and 74% (P = .03). Only patients in class III had significantly lower p53 and Rb expression (P = .017 and .001, respectively). Multivariable survival analysis confirmed the prognostic value of the three-class model.

CONCLUSION

Using this system for classification, we define the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class III). This study defines a novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies.

Authors+Show Affiliations

Department of Medical Oncology, Yale University School of Medicine, New Haven, CT, 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

16401683

Citation

Weinberger, Paul M., et al. "Molecular Classification Identifies a Subset of Human Papillomavirus--associated Oropharyngeal Cancers With Favorable Prognosis." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 24, no. 5, 2006, pp. 736-47.
Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006;24(5):736-47.
Weinberger, P. M., Yu, Z., Haffty, B. G., Kowalski, D., Harigopal, M., Brandsma, J., Sasaki, C., Joe, J., Camp, R. L., Rimm, D. L., & Psyrri, A. (2006). Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 24(5), 736-47.
Weinberger PM, et al. Molecular Classification Identifies a Subset of Human Papillomavirus--associated Oropharyngeal Cancers With Favorable Prognosis. J Clin Oncol. 2006 Feb 10;24(5):736-47. PubMed PMID: 16401683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. AU - Weinberger,Paul M, AU - Yu,Ziwei, AU - Haffty,Bruce G, AU - Kowalski,Diane, AU - Harigopal,Malini, AU - Brandsma,Janet, AU - Sasaki,Clarence, AU - Joe,John, AU - Camp,Robert L, AU - Rimm,David L, AU - Psyrri,Amanda, Y1 - 2006/01/09/ PY - 2006/1/13/pubmed PY - 2006/3/1/medline PY - 2006/1/13/entrez SP - 736 EP - 47 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 24 IS - 5 N2 - PURPOSE: We sought to determine the prevalence of biologically relevant human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC). Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis. METHODS: Using real-time polymerase chain reaction for HPV16, we determined HPV16 viral load in a cohort of 79 OSCCs annotated with long-term patient follow-up. A tissue microarray including these cases was also analyzed for p53, p16, and Rb utilizing in situ quantitative protein expression analysis. Seventy-seven tumors were classified into a three-class model on the basis of p16 expression and HPV-DNA presence: class I, HPV-, p16 low; class II, HPV+, p16 low; and class III, HPV+, p16 high. RESULTS: Sixty-one percent of OSCCs were HPV16+; HPV status alone was of no prognostic value for local recurrence and was barely significant for survival times. Overall survival was improved in class III (79%) compared with the other two classes (20% and 18%; P = .0095). Disease-free survival for the same class was 75% versus 15% and 13% (P = .0025). The 5-year local recurrence was 14% in class III versus 45% and 74% (P = .03). Only patients in class III had significantly lower p53 and Rb expression (P = .017 and .001, respectively). Multivariable survival analysis confirmed the prognostic value of the three-class model. CONCLUSION: Using this system for classification, we define the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class III). This study defines a novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/16401683/Molecular_classification_identifies_a_subset_of_human_papillomavirus__associated_oropharyngeal_cancers_with_favorable_prognosis_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2004.00.3335?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -