Characterization of the Head and Neck Papillary Squamous Cell Carcinoma Variants: Clinicopathological and Molecular Study with Special Reference to Human Papillomavirus (HPV) Association
Mitra Mehrad, Danielle H Carpenter, Rebecca D Chernock, Hongwei Wang, Xiao-Jun Ma, Yuling Luo, Jingqin Luo, James S Lewis, Samir K El-Mofty. Washington University School of Medicine, St Louis, MO; Advanced Cell Diagnostics, Inc., Hayward, CA
Background: Papillary squamous cell carcinoma (PSCC) of the head and neck (H&N) is often confused with other exophytic mucosal malignancies such as verrucous carcinoma and squamous cell carcinoma with verrucous features. The latter two entities are characterized by excessive keratinization and are broad based. A relationship to HPV infection has been suggested, however, it has not been clearly shown whether PSCC is a homogeneous entity or a spectrum of variants with different clinicopathological features and biological behaviors.
Design: 48 cases of PSCC were retrieved from our surgical pathology database and were reviewed by 3 study pathologists, following morphologic criteria as defined by the WHO. An RNA insitu hybridization (ISH) assay to detect high-risk HPV E6/E7 mRNA was used as were DNA ISH for high-risk HPV and immunohistochemistry (IHC) for p16 and p53. Clinical follow-up data were obtained by chart review.
Results: 7 cases were in the oral cavity (OC), 19 in the oropharynx (OP) and 22 in the larynx. Two morphologic types of PSCC were identified: a keratinizing type (K) in which the epithelial cells showed a maturation trend with minimal surface parakeratin, and a nonkeratinizing type (NK) in which the papillae were completely covered by immature basaloid cells. Transcriptionally active HPV was documented in a number of tumors; The majority of these were found in younger patients and occured more commonly in the OP. They showed NK morphology, were p16 positive and p53 negative.
|Site (n)||NK %||p16 + %||p53 + %||HPV + %|
|Oral (7)||14.3||14.3 (p=0.012)||71.4 (p=0.028)||57.1 (p=0.067)|
|Larynx (22)||9.0||13.6 (p=0.0005)||68.2 (p=0.004)||42.1 (p=0.020)|