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

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. SkinnerCurtis R Pickering

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 deescalation 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.

Original languageEnglish (US)
Article numbere124762
JournalJCI Insight
Volume4
Issue number1
DOIs
StatePublished - Jan 10 2019

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Squamous Cell Carcinoma
Survival
Neoplasms
Radiotherapy
Morbidity
Therapeutics
Radiation Tolerance
Clinical Protocols
Survival Rate
Biomarkers
Carcinoma
Gene Expression
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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

In: JCI Insight, Vol. 4, No. 1, e124762, 10.01.2019.

Research output: Contribution to journalArticle

Gleber-Netto, FO, Rao, X, Guo, T, Xi, Y, Gao, M, Shen, L, Erikson, K, Kalu, NN, Ren, S, Xu, G, Fisch, KM, Akagi, K, Seiwert, T, Gillison, M, Frederick, MJ, Johnson, FM, Wang, J, Myers, JN, Califano, J, Skinner, HD & Pickering, CR 2019, 'Variations in HPV function are associated with survival in squamous cell carcinoma', JCI Insight, vol. 4, no. 1, e124762. https://doi.org/10.1172/jci.insight.124762
Gleber-Netto, Frederico O. ; Rao, Xiayu ; Guo, Theresa ; Xi, Yuanxin ; Gao, Meng ; Shen, Li ; Erikson, Kelly ; Kalu, Nene N. ; Ren, Shuling ; Xu, Guorong ; Fisch, Kathleen M. ; Akagi, Keiko ; Seiwert, Tanguy ; Gillison, Maura ; Frederick, Mitchell J. ; Johnson, Faye M ; Wang, Jing ; Myers, Jeffrey N ; Califano, Joseph ; Skinner, Heath D. ; Pickering, Curtis R. / Variations in HPV function are associated with survival in squamous cell carcinoma. In: JCI Insight. 2019 ; Vol. 4, No. 1.
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AU - Shen, Li

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AU - Gillison, Maura

AU - Frederick, Mitchell J.

AU - Johnson, Faye M

AU - Wang, Jing

AU - Myers, Jeffrey N

AU - Califano, Joseph

AU - Skinner, Heath D.

AU - Pickering, Curtis R

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