Nonkeratinizing Squamous Cell Carcinoma In Situ of the Upper Aerodigestive Tract: An HPV-Related Entity

The clinical and pathologic characteristics of human papillomavirus (HPV)-related premalignant lesions in the upper aerodigestive tract have not been adequately studied. There are a few reports of oral cavity HPV-related severe dysplasia with unique morphology (prominent apoptosis/karyorrhexis imparting a ‘bowenoid’ appearance) and a single case report of HPV-related squamous cell carcinoma in situ with nonkeratinizing histology distinct from the ‘bowenoid’ pattern that extensively involved the upper aerodigestive tract. The aim of this study was to characterize the morphologic and clinical features of HPV-related severe dysplasia/carcinoma in situ. All cases of upper aerodigestive tract severe dysplasia/carcinoma in situ (111 cases from 98 patients) at Washington University from July 2012 to March 2015 were categorized into histologic types: keratinizing, nonkeratinizing, mixed or ‘bowenoid’. There were 83 (85 %) patients with keratinizing, 3 (3 %) nonkeratinizing and 12 (12 %) mixed patterns. The previously reported ‘bowenoid’ morphology was not identified. All 3 (100 %) nonkeratinizing and 6 (50 %) mixed cases were p16 and HPV RNA in situ hybridization (RNA ISH) positive (100 % concordance between p16 and RNA ISH). Only 2 of 73 keratinizing cases were p16 positive, 1 of which was also HPV RNA ISH positive (1.4 % of keratinizing cases HPV-related). Thus, nonkeratinizing morphology was a strong predictor of transcriptionally-active HPV in severe dysplasia/carcinoma in situ. HPV-related cases most commonly occurred in the floor of mouth and were frequently extensive (≥4 cm) or unresectable.