Brain metastases from Head and Neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) affects nearly 500,000 individuals globally each year. With the rise of human papillomavirus (HPV) in the general population, clinicians are seeing a concomitant rise in HPV-related HNSCC. Notably, a hallmark of HPV-related HNSCC is a predilection for unique biological and clinical features, which portend a tendency for hematogenous metastases to distant locations, such as the brain. Despite the classic belief that HNSCC is restricted to local spread via passive lymphatic drainage, brain metastases (BMs) are a rare complication that occurs in less than 1% of all HNSCC cases. Time between initial diagnosis of HNSCC and BM development can vary considerably. Some patients experience more than a decade of disease-free survival, whereas others present with definitive neurological symptoms that precede primary tumor detection 1).


Cases of metastatic squamous cell carcinoma (SCC) to the brain were identified from a computerized search of the surgical pathology files of The Johns Hopkins Hospital between 1985 and 2012. The medical records were reviewed to document primary site of tumor origin, treatment, and patient outcome. P16 immunohistochemistry and HPV in situ hybridization were performed on those metastases arising from the head and neck. Of the 38 metastatic SCCs, 7 (18 %) originated in the head and neck. HPV-16 was detected in 4 (57 %) of the metastatic HNSCCs. All 4 HPV-positive metastases were from oropharyngeal primaries. The time from treatment of the primary to development of the brain metastases ranged from 19 to 57 months (mean, 45). Following aggressive treatment (surgery and radiation), two patients died of disease progression (7 and 34 months), and two are alive with recurrent brain metastases (4 and 10 months). Although HPV positivity is regarded as a favorable prognostic indicator, it does not safeguard from spread to the brain. In our experience, just over half of the HNSCCs that metastasized to the brain were HPV-related. The potential for developing a brain metastases long after curative therapy argues for extended patient follow-up. The development of a brain metastases is an ominous finding signaling rapid clinical deterioration 2)


1)
Barrett TF, Gill CM, Miles BA, Iloreta AMC, Bakst RL, Fowkes M, Brastianos PK, Bederson JB, Shrivastava RK. Brain metastases from squamous cell carcinoma of the head and neck: a review of the literature in the genomic era. Neurosurg Focus. 2018 Jun;44(6):E11. doi: 10.3171/2018.2.FOCUS17761. PMID: 29852772.
2)
Ruzevick J, Olivi A, Westra WH. Metastatic squamous cell carcinoma to the brain: an unrecognized pattern of distant spread in patients with HPV-related head and neck cancer. J Neurooncol. 2013 May;112(3):449-54. doi: 10.1007/s11060-013-1075-9. Epub 2013 Feb 14. PMID: 23408186; PMCID: PMC3630253.
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