Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.