Keywords
human papillomavirus - squamous cell carcinoma - sinonasal - endoscopic
Introduction
Case Report
A 66-year-old otherwise healthy woman presented with a one-year history of right nasal
obstruction, maxillary tenderness, and clear rhinorrhea. Nasal endoscopy revealed
a papillary mass along the superior edge of the right inferior turbinate, indiscernible
from the middle turbinate and extending into the ethmoid sinuses ([Fig. 1]). In-office biopsy demonstrated squamous cell carcinoma (SCC) positive for high-risk
human papillomavirus (hrHPV) RNA by in situ hybridization. A diagnosis of HPV-related
multiphenotypic sinonasal carcinoma was considered but immunohistochemical staining
for Sox-10 was negative which, along with histologic findings, supported a diagnosis
of HPV-associated sinonasal SCC (HPV+ SNSCC, [Fig. 2]). MRI and CT demonstrated a 3-cm mass of the right anterior ethmoids involving the
middle turbinate, abutting the right orbit inferomedially without clear orbital invasion
([Fig. 3]). The patient opted for upfront endoscopic resection, where the tumor was found
not to invade the lamina papyracea and all final margins (including olfactory cleft
and dura) were negative for carcinoma. She underwent 60 Gy of adjuvant intensity-modulated
radiation therapy to the nasal cavity and bilateral neck, and as of most recent follow-up
5 months postoperatively she had normal visual acuity and no evidence of disease.
Fig. 1 In-office nasal endoscopy (right nasal cavity depicted) during initial evaluation
was notable for a papillary tumor along the superior edge of the right inferior turbinate
and indiscernible from the middle turbinate, extending into the right ethmoids and
adherent to the septum. IT, inferior turbinate; S, septum.
Fig. 2 Hematoxylin and eosin (H&E) tissue section from biopsy performed in the outpatient
setting, demonstrating squamous cell carcinoma. The tumor is non-keratinizing with
papillary architecture.
Fig. 3 Preoperative CT images (upper left and lower left) and preoperative T2-weighted MRI
images (upper right and lower right) showing a 3-cm mass of the right nasal cavity
indiscernible from the right middle turbinate, involving the right anterior ethmoids,
and extending into the right maxillary infundibulum. The mass is abutting the right
inferomedial orbit but is not exhibiting clear orbital invasion.
Literature Review
SNSCC is the most common malignancy of the nasal cavity and paranasal sinuses, accounting
for over half of all cases.[1] Although historically, industrial occupational exposures (particularly wood dust)
and smoking have been cited as risk factors for this disease, HPV is now recognized
as a key etiologic factor in a subset of SNSCC. Population-based data suggests that
hrHPV (most commonly HPV16) is detected in up to one-third of all SNSCC.[2]
[3]
[4] As with HPV-associated oropharyngeal SCC (HPV+ OPSCC), the incidence of HPV-associated
SNSCC (HPV+ SNSCC) has increased significantly over time, especially in younger patients.[4]
[5]
[6]
[7]
In oropharyngeal tumors, p16 immunohistochemistry is often used as a surrogate for
hrHPV infection.[8] However, p16 positivity is less specific for HPV in the nasal cavity since other
sinonasal tumors, such as adenoid cystic carcinoma, are commonly p16+ in the absence
of HPV infection.[9] Collective evidence suggests that p16 status is an unacceptable proxy for HPV in
non-oropharyngeal tumors.[10] Instead, the gold standard HPV detection method for sinonasal tumors (and all head
and neck cancers) is identification of messenger RNA for the HPV viral oncogenes E6/E7
in tumor tissue, most commonly via in situ hybridization.[8]
Rates of HPV positivity are highest in SNSCC of the nasal cavity and ethmoid sinuses
and lower in the maxillary, frontal, and sphenoid sinuses, ostensibly due to differences
in exposure to refluxed oropharyngeal secretions.[3] Recent work suggests the rise of HPV+ SNSCC in recent decades can largely be attributed
to an increased incidence of nasal cavity tumors.[11] Currently, there are no differences in management guidelines for HPV+ versus HPV−
SNSCC.[1] Upfront surgical resection with curative intent is frequently pursued for resectable
SNSCC regardless of HPV status, with adjuvant radiation or chemoradiation recommended
for high-risk pathologic features.[1]
[12]
[13] Induction chemotherapy is frequently employed in the modern era for locally advanced
(T3/T4a) tumors in an attempt to reduce tumor size and allow organ-preserving surgery
or radiation, particularly to maximize chances of orbital preservation.[14]
HPV status appears to carry significant prognostic implications in SNSCC. In a large
2019 NCDB study of SNSCC, patients with HPV+ tumors had significantly higher 3-year
overall survival compared with those with HPV− tumors (74.6% versus 56.1%, respectively).[4] A 2021 meta-analysis also found substantial differences between HPV+ versus HPV−
SNSCC with respect to both 2-year disease-free survival (81.7% versus 55.8%, respectively)
and 5-year overall survival (67.6% versus 47.6%, respectively).[15] The apparent survival benefit and high incidence of HPV positivity argues that SNSCC
should be routinely tested for HPV. Future study is needed to clarify whether treatment
de-escalation, which has been successfully adopted in HPV+ OPSCC, is also appropriate
for HPV+ SNSCC.
