Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma.

Papillary squamous cell carcinoma (SCC) is an uncommon variant of SCC in the upper aerodigestive tract. It is most frequently located in the larynx, oropharynx, and sinonasal tract, and is more common in older men. Because of its complex exophytic papillary architecture, histologic assessment of underlying invasion can be challenging. Risk factors and pathogenesis are unclear. We reviewed 31 papillary SCCs of the upper aerodigestive tract seen at our institution over a 17-year period with respect to p16 immunoreactivity and human papillomavirus (HPV) status. Twelve papillary SCCs were associated with invasive SCC in their disease course. In our study, more than two-thirds of papillary SCCs in the upper aerodigestive tract were immunoreactive with antibody to p16 and 68% of those lesions had identifiable high-risk HPV by in situ hybridization. As with other HPV-associated SCCs of the upper aerodigestive tract, the majority of HPV-associated papillary SCCs are oropharyngeal (base of tongue and palatine tonsils), although both sinonasal and laryngeal tumors were also associated with infection (67% and 33% of cases, respectively). Given the better prognosis of HPV-associated SCCs of the upper aerodigestive tract, it may be prudent to report the p16 and HPV status of these tumors when they are encountered.