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Papillary Squamous Cell Carcinoma of the Head and Neck: Clinicopathologic and Molecular Features With Special Reference to Human Papillomavirus

Mehrad, Mitra MD*; Carpenter, Danielle H. MD*; Chernock, Rebecca D. MD*,†; Wang, Hongwei MD, PhD; Ma, Xiao-Jun PhD; Luo, Yuling PhD; Luo, Jingqin PhD§; Lewis, James S. Jr MD*,†; El-Mofty, Samir K. DMD, PhD*,†

American Journal of Surgical Pathology: September 2013 - Volume 37 - Issue 9 - p 1349–1356
doi: 10.1097/PAS.0b013e318290427d
Original Articles

A relationship between human papillomavirus (HPV) infection and papillary squamous cell carcinoma (PSCC) has been suggested. However, to date, no studies have thoroughly and directly evaluated for transcriptional activity of the virus or the clinicopathologic significance of HPV-positive PSCC. Forty-eight cases of PSCC were retrieved from our surgical pathology database and were reviewed by 4 study pathologists, with tumors defined as SCC with a significant component of papillary growth in the tumor. Immunohistochemical analysis for p16 and p53 was performed. Overexpression of p16 was used as a surrogate marker of transcriptionally active HPV. Transcriptional activity was also directly evaluated using RNA in situ hybridization to detect high-risk HPV E6/E7 mRNA. Clinical follow-up data were obtained by chart review. Seven cases were located in the oral cavity, 19 in the oropharynx, and 22 in the larynx. Two morphologic types of PSCC were identified: keratinizing type, in which the epithelial cells showed a maturation trend with minimal surface parakeratin, and nonkeratinizing type, in which the papillae were completely covered by immature basaloid cells. Transcriptionally active HPV was present in 23 of 43 (53.4%) tumors. The majority of tumors harboring transcriptionally active HPV arose in the oropharynx, showed nonkeratinizing morphology, were p16 positive, and p53 negative. Transcriptionally active HPV was also present in many laryngeal and oral cavity PSCCs. Overall survival, disease-specific survival, and disease-free survival were favorable and did not significantly differ by anatomic subsite. However, HPV-related tumors showed a trend toward better survival.

Departments of *Pathology and Immunology

Department of Otolaryngology Head and Neck Surgery

§Division of Biostatistics, Washington University School of Medicine, St Louis, MO

Advanced Cell Diagnostics Inc., Hayward, CA

Presented at the United States and Canadian Academy of Pathology, 101st Annual Meeting, Vancouver, BC, Canada, 2012.

Conflicts of Interest and Source of Funding: The RNA in situ hybridization assays in the work were funded and performed by the coauthors from Advanced Cell Diagnostics Inc., Hayward, CA. Three coauthors, H.W., Y.L., X.-J.M., have stock in this company and stand to profit by any use of this testing through their company. For the remaining authors none were declared.

Correspondence: Mitra Mehrad, MD, Department of Pathology and Immunology, Washington University School of Medicine, 660S, Euclid Ave., Campus Box 8118, St Louis, MO 63110 (e-mail: mmehrad@path.wustl.edu).

© 2013 by Lippincott Williams & Wilkins.