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Publication
Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human
Papillomavirus Type and by 16 Lineages and Sublineages.
Authors Lewis JS, Mirabello L, Liu P, Wang X, Dupont WD, Plummer WD, Pinheiro M, Yeager
M, Boland JF, Cullen M, Steinberg M, Bass S, Mehrad M, O'Boyle C, Lin M, Faden
DL, Lang-Kuhs KA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Head and neck pathology
Year 2021
Date Published 12/1/2021
Volume : Pages 15 : 1089 - 1098
PubMed Reference 33797697
Abstract 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.




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