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Head and Neck Pathology
Published in: Head and Neck Pathology 1/2012

01-07-2012 | Invited Review

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Author: James S. Lewis Jr.

Published in: Head and Neck Pathology | Special Issue 1/2012

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Abstract

It is widely acknowledged that human papillomavirus (HPV)-related oropharyngeal carcinoma is a biologically unique form of head and neck cancer that should be singled out and treated differently. It is now incumbent to find a test (or combination of tests) that accurately identifies cancers with the associated favorable prognosis for proper patient counseling and management and for placing patients in the correct treatment arms in the emerging clinical trials that are attempting to establish unique treatment types and approaches. The test (or combination of tests) that are utilized must be widely available, reliable, easy to interpret, and well-validated. While HPV-specific testing seems completely logical to use as a single test or one of a combination of tests, it turns out to be quite complicated in practice. Because of the different forms of the virus, the differing types of HPV-specific tests can give different information. HPV DNA, RNA, and protein assays have varying sensitivities for virus detection and also varying availability from formalin-fixed, paraffin-embedded tissue. Since p16 protein over expression is very sensitive for the presence of transcriptionally-active HPV and since it correlates strongly with patient outcomes, is widely available, and easy to interpret, it appears to currently be the single test that combines all of the desired attributes in a risk stratification marker for widespread implementation in clinical and research study settings. This article will review the literature on p16 immunohistochemistry and its relation to HPV-specific testing, discuss some practical issues related to its implementation, and present the case for why it should be the single test used for this purpose.
Literature
1.
Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol. 2010;46(7):492–6.PubMedCrossRef
2.
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.PubMedCrossRef
3.
Reimers N, Kasper HU, Weissenborn SJ, et al. Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer. 2007;120(8):1731–8.PubMedCrossRef
4.
Syrjanen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol. 2005;32(Suppl 1):S59–66.PubMedCrossRef
5.
Lewis JS Jr, Thorstad WL, Chernock RD, et al. p16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8):1088–96.PubMedCrossRef
6.
Shi W, Kato H, Perez-Ordonez B, et al. Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. J Clin Oncol. 2009;27(36):6213–21.PubMedCrossRef
7.
Schache AG, Liloglou T, Risk JM, et al. Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res. 2011;17(19):6262–71.PubMedCrossRef
8.
Schlecht NF, Brandwein-Gensler M, Nuovo GJ, et al. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol. 2011;24(10):1295–305.PubMedCrossRef
9.
Ukpo OC, Flanagan JJ, Ma XJ, et al. High risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol. 2011;35:1343–50.PubMedCrossRef
10.
Thavaraj S, Stokes A, Guerra E, et al. Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice. J Clin Pathol. 2011;64(4):308–12.PubMedCrossRef
11.
Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer. 2010;116(9):2166–73.PubMed
12.
Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28(27):4142–8.PubMedCrossRef
13.
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.PubMedCrossRef
14.
Dahlstrand H, Nasman A, Romanitan M. Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer. Anticancer Res. 2008;28(2B):1133–8.PubMed
15.
Doxtader EE, Katzenstein AL. The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinomas from sites other than uterine cervix: a study of 137 cases. Hum Pathol. 2012;43(3):327–32. PubMedCrossRef
16.
Perrone F, Gloghini A, Cortelazzi B, et al. Isolating p16-positive/HPV-negative oropharyngeal cancer: an effort worth making. Am J Surg Pathol. 2011;35(5):774–7. (author reply 777–778).PubMedCrossRef
17.
Wadsworth B, Bumpous JM, Martin AW, et al. Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV). Head Neck Pathol. 2011;5(4):349–54.PubMedCrossRef
18.
Tong J, Sun X, Cheng H, et al. Expression of p16 in non-small cell lung cancer and its prognostic significance: a meta-analysis of published literatures. Lung Cancer. 2011;74(2):155–63.PubMedCrossRef
19.
Fischer CA, Zlobec I, Green E, et al. Is the improved prognosis of p16 positive oropharyngeal squamous cell carcinoma dependent of the treatment modality? Int J Cancer. 2010;126(5):1256–62.PubMed
20.
Granata R, Miceli R, Orlandi E et al.: Tumor stage, human papillomavirus and smoking status affect the survival of patients with oropharyngeal cancer: an Italian validation study. Ann Oncol; 2011 [epub ahead of print].
21.
Weinberger PM, Yu Z, Haffty BG, et al. Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res. 2004;10(17):5684–91.PubMedCrossRef
22.
Chernock RD, El-Mofty SK, Thorstad WL, et al. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol. 2009;3(3):186–94.PubMedCrossRef
23.
Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.PubMedCrossRef
24.
Singhi AD, Stelow EB, Mills SE, et al. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34(6):800–5.PubMedCrossRef
25.
Masand RP, El-Mofty SK, Ma XJ, et al. Adenosquamous carcinoma of the head and neck: relationship to human papillomavirus and review of the literature. Head Neck Pathol. 2011;5(2):108–16.PubMedCrossRef
26.
Huak CY. Are you a p-value worshipper? Eur J Dent. 2009;3(3):161–4.PubMed
27.
Lassen P, Eriksen JG, Hamilton-Dutoit S, et al. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992–8.PubMedCrossRef
28.
Kong CS, Narasimhan B, Cao H, et al. The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2009;74(2):553–61.PubMedCrossRef
29.
Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429–35.PubMedCrossRef
30.
Pfister DG, Ang KK, Brizel DM, et al. National comprehensive cancer network clinical practice guidelines in oncology. Head and neck cancers. J Natl Compr Canc Netw. 2011;9(6):596–650.PubMed
Metadata
Title
p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma
Author
James S. Lewis Jr.
Publication date
01-07-2012
Publisher
Springer US
Published in
Head and Neck Pathology / Issue Special Issue 1/2012
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-012-0369-0

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