Variations in HPV function are associated with survival in squamous cell carcinoma
| Autor: | Kathleen M. Fisch, Jeffrey N. Myers, Li Shen, Meng Gao, Nene N. Kalu, Heath D. Skinner, Faye M. Johnson, Jing Wang, Yuanxin Xi, Shuling Ren, Curtis R. Pickering, Keiko Akagi, Theresa Guo, Maura L. Gillison, Tanguy Y. Seiwert, Guorong Xu, Joseph A. Califano, Kelly Erikson, Frederico O. Gleber-Netto, Mitchell J. Frederick, Xiayu Rao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Treatment response medicine.medical_treatment Cervical Cancer 03 medical and health sciences 0302 clinical medicine Radiation sensitivity Clinical Research Virology Internal medicine medicine 2.1 Biological and endogenous factors Basal cell Dental/Oral and Craniofacial Disease Aetiology Expression profiling Cancer Cervical cancer business.industry Incidence (epidemiology) Head & neck cancer General Medicine medicine.disease Gene expression profiling Radiation therapy Infectious Diseases Good Health and Well Being 030104 developmental biology 030220 oncology & carcinogenesis Sexually Transmitted Infections HIV/AIDS Digestive Diseases business Research Article |
| Zdroj: | JCI insight, vol 4, iss 1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|