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Variations in HPV function are associated with survival in squamous cell carcinoma
Frederico O. Gleber-Netto, … , Heath D. Skinner, Curtis R. Pickering
Frederico O. Gleber-Netto, … , Heath D. Skinner, Curtis R. Pickering
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e124762. https://doi.org/10.1172/jci.insight.124762.
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Research Article Oncology Virology

Variations in HPV function are associated with survival in squamous cell carcinoma

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Abstract

Incidence of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has been increasing dramatically. Although long-term survival rates for these patients are high, they often suffer from permanent radiotherapy-related morbidity. This has prompted the development of de-escalation clinical protocols to reduce morbidity. However, a subset of patients do not respond even to standard therapy and have poor outcomes. It is unclear how to properly identify and treat the high- and low-risk HPV+ OPSCC patients. Since HPV positivity drives radiotherapy sensitivity, we hypothesized that variations in HPV biology may cause differences in treatment response and outcome. By analyzing gene expression data, we identified variations in HPV-related molecules among HPV+ OPSCC. A subset of tumors presented a molecular profile distinct from that of typical HPV+ tumors and exhibited poor treatment response, indicating molecular and clinical similarities with HPV– tumors. These molecular changes were also observed in vitro and correlated with radiation sensitivity. Finally, we developed a prognostic biomarker signature for identification of this subgroup of HPV+ OPSCC and validated it in independent cohorts of oropharyngeal and cervical carcinomas. These findings could translate to improved patient stratification for treatment deintensification and new therapeutic approaches for treatment-resistant HPV-related cancer.

Authors

Frederico O. Gleber-Netto, Xiayu Rao, Theresa Guo, Yuanxin Xi, Meng Gao, Li Shen, Kelly Erikson, Nene N. Kalu, Shuling Ren, Guorong Xu, Kathleen M. Fisch, Keiko Akagi, Tanguy Seiwert, Maura Gillison, Mitchell J. Frederick, Faye M. Johnson, Jing Wang, Jeffrey N. Myers, Joseph Califano, Heath D. Skinner, Curtis R. Pickering

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Usage data is cumulative from December 2022 through December 2023.

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PDF 65 76
Figure 209 12
Table 34 0
Supplemental data 70 12
Citation downloads 26 0
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Total Views 1,782
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