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Human Papillomavirus–related Carcinoma With Adenoid Cystic–like Features: A Peculiar Variant of Head and Neck Cancer Restricted to the Sinonasal Tract

Bishop, Justin A. MD*; Ogawa, Takenori MD, PhD; Stelow, Edward B. MD; Moskaluk, Christopher A. MD, PhD; Koch, Wayne M. MD; Pai, Sara I. MD, PhD; Westra, William H. MD*,†,§

The American Journal of Surgical Pathology: June 2013 - Volume 37 - Issue 6 - p 836–844
doi: 10.1097/PAS.0b013e31827b1cd6
Original Articles

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.

*Departments of Pathology

Otolaryngology/Head and Neck Surgery

§Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD

Department of Pathology, The University of Virginia, Charlottesville, VA

Conflicts of Interest and Source of Funding: Partially funded by the National Institute of Dental and Craniofacial Research (R01 DE013152-11). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: William H. Westra, MD, Department of Pathology, The Johns Hopkins University School of Medicine, 401 N Broadway, Weinberg 2242, Baltimore, MD 21231 (e-mail

© 2013 Lippincott Williams & Wilkins, Inc.