HPV and Head and Neck Cancer
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2 William C. Faquin, MD, PhD, FCAP Director, Head and Neck Pathology Massachusetts General Hospital Associate Professor of Pathology Harvard Medical School HPV and Head and Neck Cancer A number of testing methodologies (e.g. p16, PCR, RT-PCR, DNA ISH, mrna ISH, cytologybased) are available for detecting high-risk human papillomavirus (HPV) in head and neck squamous cell carcinomas (HNSCC). However, these tests vary in their sensitivities and specificities for detecting HPV as well as in their cost and technical difficulty. The HPV status of HNSCC of the oropharynx is currently used to predict prognosis and is also being used in the setting of clinical trials to determine therapy. However, poor analytical sensitivities and specificities of selected tests can result in detection errors. This session will present a review of the role of HPV in head and neck cancer with an emphasis on the oropharynx. Additionally, the session will cover available testing methodologies and their limitations, as well as review the evidence-based guidelines currently in development by the CAP Pathology and Laboratory Quality Center. The goals of this presentation are the following: Recognize the role of HR-HPV in head and neck carcinogenesis Assess the various high-risk HPV testing methods including surrogate markers for patients being evaluated for carcinomas of the head and neck Review the current CAP effort to establish guidelines for HPV reflex testing for head and neck carcinomas Ensure proper use of HPV testing and surrogate markers for head and neck carcinomas Assess the changes needed to comply with the testing guidelines
3 Selected References: Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. The New England journal of medicine 2010;363: Bishop JA, Ma XJ, Wang H, et al. Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mrna in situ hybridization method. The American journal of surgical pathology 2012;36: Bishop JA, Maleki Z, Valsamakis A, et al. Application of the hybrid capture 2 assay to squamous cell carcinomas of the head and neck: a convenient liquid-phase approach for the reliable determination of human papillomavirus status. Cancer cytopathology 2012;120: Bonilla-Velez J, Mroz EA, Hammon RJ, Rocco JW. Impact of human papillomavirus on oropharyngeal cancer biology and response to therapy: implications for treatment. Otolaryngol Clin North Am 2013;46: Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29: Chernock RD, Wang X, Gao G, et al. Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2013;26: Chute DJ, Aramouni G, Brainard J, Hoschar A, Kroger A, Yen-Lieberman B. Hybrid Capture 2 Human Papilloma Virus Testing for Head and Neck Cytology Specimens. Journal of the American Society of Cytopathology 2014;3. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. The New England journal of medicine 2007;356: El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. The American journal of surgical pathology 2005;29: Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomaviruspositive head and neck squamous cell carcinoma in a prospective clinical trial. Journal of the National Cancer Institute 2008;100: Faquin WC. Human papilloma virus assays for testing fine-needle aspiration specimens in patients with head and neck squamous cell carcinoma. Cancer Cytopathology 2014;
4 Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. Journal of the National Cancer Institute 2000;92: Guo M, Khanna A, Dhillon J, et al. Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma. Cancer cytopathology 2014;122: Holmes BJ, Westra WH. The expanding role of cytopathology in the diagnosis of HPV-related squamous cell carcinoma of the head and neck. Diagnostic cytopathology 2014;42: Jordan RC, Lingen MW, Perez-Ordonez B, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. The American journal of surgical pathology 2012;36: Kerr DA, Arora KS, Mahadevan KK, Hornick JL, Krane JF, Rivera MN, Ting DT, Deshpande V, Faquin WC. Performance of a branch chain RNA in situ hybridization assay for the detection of high-risk human papillomavirus in head and neck squamous cell carcinoma. Am J Surg Pathol 2015;39(12): Kerr DA, Pitman MB, Sweeney B, Arpin RN, Wilbur DC, Faquin WC. Performance of the Roche cobas 4800 high risk HPV test in cytologic preparations of squamous cell carcinoma of the head and neck. Cancer Cytopathol 2014;122: Lewis JS, Jr., Ukpo OC, Ma XJ, et al. Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas--a tissue microarray study utilizing E6/E7 mrna in situ hybridization. Histopathology 2012;60: Lewis JS, Jr., Westra WH, Thompson LD, et al. The Sinonasal Tract: Another Potential "Hot Spot" for Carcinomas with Transcriptionally-Active Human Papillomavirus. Head and neck pathology 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. The American journal of surgical pathology 2010;34: Lewis JS Jr., Chernock RD, Ma XJ, Flanagan JJ, Luo Y, Gao G, Wang X, El-Mofty SK. Partial p16 staining in oropharyngeal squamous cell carcinoma extent and pattern correlate with human papillomavirus status Mod Pathol 25(9): Lingen MW, Xiao W, Schmitt A, et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol 2013;49:1-8. Maniakas A, Moubayed SP, Ayad T, et al. North-American survey on HPV-DNA and p16 testing for head and neck squamous cell carcinoma. Oral Oncol 2014.
5 Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virusrelated cancer epidemic. The lancet oncology 2010;11: 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: Shoushtari AN, Rahimi NP, Schlesinger DJ, Read PW. Survey on human papillomavirus/p16 screening use in oropharyngeal carcinoma patients in the United States. Cancer 2010;116: 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: Ukpo OC, Flanagan JJ, Ma XJ, Luo Y, Thorstad WL, Lewis JS, Jr. 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. The American journal of surgical pathology 2011;35: Witt BL, Albertson DJ, Coppin MG, Horrocks CF, Post M, Gulbahce HE. Use of In Situ Hybridization for HPV in Head and Neck Tumors: Experience from a National Reference Laboratory. Head and neck pathology 2014.
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