Poor prognosis in human papillomavirus–positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor‐1α

Swartz, Justin E.; Pothen, Ajit J.; Kempen, Pauline M.W. van; Stegeman, Inge; Formsma, Fleurieke Karlijn; Cann, Ellen M. Van; Willems, Stefan M.; Grolman, Wilko

doi:10.1002/hed.24445

Cited by 42 publications

(33 citation statements)

References 34 publications

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“…Meanwhile, Ayala and colleagues [13] also identified GLUT-1 as an indicator for poor overall survival ( P = 0.006) in their study. Swartz et al [15] also found significantly prognostic role of GLUT-1 in OSCC by univariate overall survival analysis ( P = 0.026). In contrast, other studies did not find any significant association between GLUT-1 and outcome of OSCC patients.…”

Section: Introductionmentioning

confidence: 89%

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

Sun

Gong

et al. 2016

Medicine

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Background:A variety of studies have evaluated the correlation between glucose transporter-1 (GLUT-1) expression and prognosis of oral squamous cell carcinoma (OSCC); however, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the prognostic significance of GLUT-1 in OSCC.Methods:Electronic databases of PubMed, Embase, and Web of Science were searched for relevant studies. The last search was updated on July 2016. Odds ratio (OR) and 95% confidence interval (CI) were pooled to evaluate the relationship between GLUT-1 and clinical features and hazard ratio (HR) and 95% CI were combined to measure the effect of GLUT-1 on overall survival (OS). P value < 0.05 was considered as statistically significant.Results:A total of 13 studies with 1301 subjects were included for meta-analysis. The pooled data showed that high GLUT-1 expression was associated with advanced tumor stages (n = 7, OR = 2.99, 95% CI: 2.01–4.46, P < 0.001), higher tumor grade (n = 5, OR = 3.34, 95%CI: 1.12–9.94, P = 0.031), tumor size (n = 5, OR = 3.36, 95%CI: 2.04–5.51, P < 0.001), lymph node metastasis (n = 5, OR = 3.15, 95%CI: 1.89–5.25, P < 0.001), tobacco use (n = 3, OR = 2.18, 95%CI: 1.18–4.01, P = 0.013), and distant metastasis (n = 2, OR = 3.06, 95%CI: 1.19–7.9, P = 0.02). Furthermore, increased GLUT-1 expression was also correlated with shorter OS (n = 8, HR = 1.88, 95%CI: 1.51–2.33, P < 0.001). No significant publication bias was detected in this meta-analysis.Conclusion:GLUT-1 overexpression was in connection with aggressive clinical features and worse OS in OSCC. However, further studies are still needed to verify whether GLUT-1 could serve as a prognostic biomarker for OSCC.

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Section: Introductionmentioning

confidence: 89%

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

Sun

Gong

et al. 2016

Medicine

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“…HNSCC tumours are also characterized by hypoxia, with roughly similar levels of hypoxia in HPV-positive and HPV-negative tumours of the same stage 119 . High levels of hypoxia in tumours portend a poor prognosis and resistance to radiation therapy [120][121][122][123][124] . Hypoxia induces the expression of HIF1α, a subunit of the transcription factor HIF1, which drives expression of a range of genes encoding proteins that promote angiogenesis (VEGF) and degradation of ECM (MMPs).…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

Head and neck squamous cell carcinoma

Johnson

Burtness

Leemans

et al. 2020

Nat Rev Dis Primers

2,465

1,926

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Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.

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“…HIF-1α overexpression has been associated with poor prognosis, advanced disease, an aggressive cancer phenotype and poor response to radiotherapy in a number of malignancies, including HNSCC. 46 There is clear clinical utility to using hypoxia-related proteins such as CAIX or HIF-1α as surrogate markers of tumour hypoxia as they can be easily detected in tissue samples, have low assay costs, offer the potential of marker co-detection and the possibility of repeatedly detecting and monitoring biomarkers when samples are available. Extrinsic markers of hypoxia such as EF5 and pimonidazole are non-physiologic substances that are injected into the body where they accumulate under hypoxic conditions as a result of chemical reduction and covalent binding to macromolecules.…”

Section: Hypoxia Detection and Patient Stratificationmentioning

confidence: 99%

HPV, hypoxia and radiation response in head and neck cancer

Göttgens

Ostheimer

Span

et al. 2018

BJR

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Over the last decades, the incidence of human papilloma virus (HPV) positive head and neck squamous-cell carcinoma (HNSCC) has significantly increased. Infection with high-risk HPV types drives tumourigenesis through expression of the oncoproteins E6 and E7. Currently, the primary treatment of HNSCC consists of radiotherapy, often combined with platinum-based chemotherapeutics. One of the common features of HNSCC is the occurrence of tumour hypoxia, which impairs the efficacy of radiotherapy and is a negative prognostic factor. Therefore, it is important to detect and quantify the severity of hypoxia, as well as develop strategies to specifically target hypoxic tumours. HPV-positive tumours are remarkably radiosensitive compared to HPV-negative tumours and consequently the HPV-positive patients have a better prognosis. This provides an opportunity to elucidate mechanisms of radiation sensitivity, which may reveal targets for improved therapy for HPV-negative head and neck cancers. In this review, we will discuss the differences between HPV-positive and HPV-negative head and neck tumours and methods of hypoxia detection and targeting in these disease types. Particular emphasis will be placed on the mechanisms by which HPV infection impacts radiosensitivity.

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Poor prognosis in human papillomavirus–positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor‐1α

Cited by 42 publications

References 34 publications

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

Head and neck squamous cell carcinoma

HPV, hypoxia and radiation response in head and neck cancer

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