Human Papillomavirus-related Carcinomas of the Sinonasal Tract.
ABSTRACT High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.
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ABSTRACT: Human papillomavirus (HPV)-related carcinomas of the head and neck are characterized by a predilection for the oropharynx, a nonkeratinizing squamous morphology, and infection with the HPV 16 type; but comprehensive HPV testing across all head and neck sites has shown that the pathologic features of HPV-related carcinoma may be more wide ranging than initially anticipated. In particular, a subset of sinonasal carcinomas are HPV positive, and these include a variant that is histologically similar to adenoid cystic carcinoma (ACC). Cases were identified by retrospective and prospective analyses of head and neck carcinomas with ACC features. HPV analysis was performed using p16 immunohistochemistry and high-risk HPV in situ hybridization. HPV-positive cases were confirmed and typed using HPV type-specific quantitative polymerase chain reaction and further characterized on the basis of their immunohistochemical profile and MYB gene status. HPV was detected in 8 carcinomas of the sinonasal tract, but it was not detected in any ACCs arising outside of the sinonasal tract. The HPV types were 33 (n=6), 35 (n=1), and indeterminate (n=1). Six patients were women, and 2 were men, ranging in age from 40 to 73 years (mean 55 y). The carcinomas were characterized by a nested growth, a prominent basaloid component showing myoepithelial differentiation and forming microcystic spaces, and a minor epithelial component with ductal structures. Squamous differentiation, when present, was restricted to the surface epithelium. The carcinomas were not associated with the MYB gene rearrangement that characterizes a subset of ACCs. These cases draw attention to an unusual variant of HPV-related carcinoma that has a predilection for the sinonasal tract. Despite significant morphologic overlap with ACC, it is distinct in several respects including an association with surface squamous dysplasia, absence of the MYB gene rearrangement, and an association with HPV, particularly type 33. As HPV positivity confers distinct clinicopathologic characteristics when encountered in the oropharynx, a more comprehensive analysis of risk factors, response to therapy, and clinical outcomes is warranted for HPV-related carcinomas of the sinonasal tract.The American journal of surgical pathology 04/2013; DOI:10.1097/PAS.0b013e31827b1cd6 · 4.59 Impact Factor
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ABSTRACT: The role of human papilloma viruses (HPV) in malignant and nonmalignant ENT diseases and the corresponding epidemiological burden has been widely described. International head and neck oncology community discussed growing evidence that oral HPV infection contributes to the risk of oro-pharyngeal carcinoma (OPC) and recommended HPV testing as a part of the work up for patients with OPC. Polish Society of ENT Head Neck Surgery and National Chamber of Laboratory Diagnosticians have worked together to define the minimum requirements for assigning a diagnosis of HPV-related conditions and testing strategy that include HPV specific tests in our country. This paper briefly frames the literature information concerning low risk (LR) and high risk (HR) HPV, reviews the epidemiology, general guidance on the most appropriate biomarkers for clinical assessment of HPV. The definition of HPV-related cancer was presented. The article is aiming to highlight some of major issues for the clinician dealing with patients with HPV-related morbidities and to introduce the diagnostic algorithm in Poland.Otolaryngologia polska. The Polish otolaryngology 05/2013; 67(3):113-134. DOI:10.1016/j.otpol.2013.01.003
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ABSTRACT: Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Recently, an association has been reported between oropharyngeal SCNEC and high-risk human papillomavirus (HPV) infection. While HPV infection confers a better prognosis for oropharyngeal squamous cell carcinoma, HPV infection does not appear to influence the biological behaviour of SCNECs, which are generally associated with poor clinical outcomes. We document two cases of SCNEC arising in the oropharynx with evidence of high-risk HPV infection. The cases highlight the expanding range of malignant oropharyngeal neoplasms that harbour oncogenic HPV infection and support the concept that, irrespective of HPV infection, neuroendocrine differentiation portends a poor prognosis.Head and Neck Pathology 07/2013; DOI:10.1007/s12105-013-0471-y