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Improved outcomes in PI3K-pathway-altered metastatic HPV oropharyngeal cancer
Glenn J. Hanna, … , Robert I. Haddad, Laura E. MacConaill
Glenn J. Hanna, … , Robert I. Haddad, Laura E. MacConaill
Published September 6, 2018
Citation Information: JCI Insight. 2018;3(17):e122799. https://doi.org/10.1172/jci.insight.122799.
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Research Article Genetics Oncology

Improved outcomes in PI3K-pathway-altered metastatic HPV oropharyngeal cancer

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Abstract

While it has been recognized that human papillomavirus–associated (HPV-associated) oropharyngeal cancer (OPC) portends an improved prognosis, distinct patterns of disease recurrence have emerged. Molecular characterization of this subset of HPV patients remains unexplored. We evaluated 52 metastatic HPV+ OPC patients from our institution and paired massively parallel sequencing data with clinical parameters and survival outcomes in 81% of patients. Genomic data were then compared with 2 molecularly defined, curable HPV+ cohorts. Metastatic HPV+ OPC patients with pulmonary-only metastases demonstrated worse outcomes. Nonexclusive somatic alterations in KMT2D and PIK3CA were most frequent, with PRKDC alterations occurring at higher frequency when compared with all sequenced HPV+ OPC patients. PI3K pathway alterations were associated with improved outcomes among metastatic HPV+ OPC patients. We demonstrate subtle differences in the mutational landscape between curable and metastatic HPV+ OPC populations, with a trend towards more frequent DNA repair protein alterations in the latter. We demonstrate improved outcomes when PI3K pathway alterations are present in these patients. We provide molecular insights for this important HPV+ subgroup that have significant therapeutic implications.

Authors

Glenn J. Hanna, Alec Kacew, Nicole G. Chau, Priyanka Shivdasani, Jochen H. Lorch, Ravindra Uppaluri, Robert I. Haddad, Laura E. MacConaill

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Figure 1

Survival outcomes in patients with metastatic HPV-associated oropharyngeal cancer.

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Survival outcomes in patients with metastatic HPV-associated oropharynge...
(A) Overall survival (in months) among n = 52 patients with metastatic oropharyngeal cancer causally related to human papillomavirus (HPV). Dotted lines represent 95% confidence intervals. Overall survival among metastatic HPV-associated oropharyngeal cancer patients based on (B) smoking history, and (C) metastatic site of disease. The pulmonary subgroup represents those with lung involvement as their only known site of distant disease, while the extrapulmonary subgroup signifies the patient had at least one site of involvement outside the lungs. HR, hazard ratio; CI, confidence interval. *P < 0.05, log-rank testing.

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