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Page 6 of 10 Sell et al. Mini-invasive Surg 2024;8:3 https://dx.doi.org/10.20517/2574-1225.2023.105

The World Health Organization (WHO) described human papillomavirus (HPV)-related multiphenotypic
sinonasal carcinoma as an updated, new subtype of nonkeratinizing SCC of the sinonasal tract in 2017.
HPV-related multiphenotypic sinonasal carcinoma is associated with greater five-year OS, including
[60]
HPV-related oropharyngeal SCC, despite its aggressive histopathology . Commonly defined by p16
overexpression, HPV-positive tumors are characterized by basaloid proliferation combined with focal areas
of squamous differentiation on histopathology. Zupancic and Näsman performed a systematic review and
found that 77 of 79 (97.5%) cases of HPV-related multiphenotypic sinonasal carcinoma occurred within the
[61]
sinonasal cavity with no regional metastasis, while one occurred in the breasts, and one in the tonsils .
Additionally, given that approximately one-third of SNSCCs are HPV-associated , circulating HPV DNA
[62]
(ctHPVDNA) is being investigated as a noninvasive biomarker of disease status both at diagnosis and
[63]
throughout treatment . Studies have demonstrated that HPV-associated SNSCC may have genotype
distributions distinct from HPV+ oropharyngeal carcinoma, with HPV 16 being less common . Further
[64]
studies are needed to investigate the genotype distributions of HPV-related multiphenotypic sinonasal
carcinoma and the utility of ctHPVDNA in the diagnosis and management of this disease. Although these
findings could have implications for optimal surveillance timing for patients with HPV-related
multiphenotypic sinonasal carcinoma, routine HPV testing for non-oropharyngeal head and neck primary
tumors is not currently recommended by the College of American Pathologists given the lack of prospective
trials and clear data determining prognostic significance .
[65]
EMERGING SURVEILLANCE STRATEGIES AND LIFETIME SURVEILLANCE
For patients with extranodal Nk/T-cell lymphoma of the sinonasal tract, in addition to endoscopy and
[66]
symptom-guided imaging, disease surveillance can include plasma Ebstein-Barr Virus (EBV) DNA titers .
In one study, patients with EBV DNA levels were used to develop the prognostic index of natural killer
lymphoma (PINK-E) score which risk stratifies patients into low, intermediate, and high-risk cohorts.
Reports of late relapses, even up to three decades after remission, have been reported for extranodal
Nk/T-cell lymphoma, making the role of EBV DNA titers for surveillance particularly important . Patients
[67]
with late relapses were found to have a prognosis comparable to that of patients with primary extranodal
Nk/T-cell lymphoma, rather than those with the typically more aggressive relapsing disease . These
[68]
[69]
patients also have an increased risk of developing treatment-related acute myeloid leukemia . Thus, for
patients with extranodal Nk/T-cell lymphoma, lifelong surveillance is recommended.

Long-term surveillance beyond the standard five years is also recommended for patients with olfactory
[70]
neuroblastoma, with local recurrence rates up to 20%-40% at ten years posttreatment . Optimal
surveillance of patients with olfactory neuroblastoma following primary treatment remains unclear;
nevertheless, one protocol recommended MRI studies at baseline of both the brain and maxillofacial area
every 2-4 months after treatment, followed by serial imaging studies at four or six-month intervals for five
years, and then annual imaging studies for the lifetime of the patient . The study recommends that
[71]
examinations include endoscopy and overlap with the surveillance imaging timetable, and further imaging
should be directed by patient-reported symptoms and examination findings.

CONCLUSION
Malignancies of the sinonasal tract are unique among head and neck cancers and require a nuanced
approach to surveillance following primary treatment. Inflammation and postsurgical changes can persist
appreciably longer than other head and neck cancers, which has implications for the ideal timing of
surveillance imaging, particularly PET/CT. Endoscopy is an important part of surveillance following
primary treatment and is most valuable when partnered with a thorough history and physical exam, probing
for potential symptoms of recurrence. MRI is the gold standard imaging modality for surveillance for