The role of HPV RNA transcription, immune response‐related gene expression and disruptive<i>TP53</i>mutations in diagnostic and prognostic profiling of head and neck cancer

Wichmann, Gunnar; Rosołowski, Maciej; Krohn, Knut; Kreuz, Markus; Boehm, Andreas; Reiche, Anett; Scharrer, Ulrike; Halama, Dirk; Bertolini, Julia; Bauer, Ulrike; Holzinger, Dana; Pawlita, Michael; Heß, Jochen; Engel, Christoph; Hasenclever, Dirk; Scholz, Markus; Ahnert, Peter; Kirsten, Holger; Hemprich, Alexander; Wittekind, Christian; Herbarth, Olf; Horn, Friedemann; Dietz, Andreas; Loeffler, Markus

doi:10.1002/ijc.29649

Cited by 198 publications

(211 citation statements)

References 44 publications

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“…In addition, there was an association between higher Ki-67 expression and metastases in SACC patients. In HNSCC, HPV-negative tumors appear to be enriched for EGFR and TP53 mutations (25). Herein, there were no correlations of HPV status with p53, EGFR and Ki-67 expression in SACC.…”

Section: Discussionmentioning

confidence: 67%

“…In HNSCC, HPV-positive tumors are characterized by certain clinical and pathological characteristics, the expression of certain cell cycle proteins and genetic changes that are different from HPV-negative HNSCC (24,25). TP53 mutations are by far the most common and present in ~70% of HPV-negative HNSCC patients, but rare in HPV-related HNSCC as p53 is targeted by E6 protein (26).…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands

Qian

Kaufmann

Chen

et al. 2016

International Journal of Oncology

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Abstract. Adenoid cystic carcinoma (SACC) is a rare malignancy, but a frequent subtype in minor and major salivary glands. The molecular alterations or biomarkers that underlie its development and progression as well as therapy outcomes are poorly characterized. The main study goal was to investigate reliable biomarkers and patient-related factors that may have impact on recurrence and long-term survival of SACC. The prevalence of human papilloma virus (HPV) in SACC was determined by HPV-DNA genotyping and p16 immunostaining. Epithelial growth factor receptor (EGFR), p53 and Ki-67 expression were also evaluated. Twenty-eight (42%) of 67 patients were HPV-DNA positive. Kaplan-Meier analysis indicated that SACC patients with metastases (P=0.03) had a poor overall survival (OS) and a shorter recurrence-free survival (P<0.001). Positive resection margins significantly predicted shorter recurrence-free survival (P=0.01). In the multivariate analysis, non-metastatic disease (P=0.033) and p16 positivity (P=0.005) have shown their prediction value for OS while non-metastatic disease (P=0.002), HPV positivity (P=0.041) and negative resection margin predicted a better recurrence-free survival. The present study documents for the first time the positivity for HPV infection and overexpression of certain markers (p16, Ki-67, EGFR and p53) used in diagnostics in SACC as well as characterizes clinical entities. These factors might be exploited in the future as biomarkers for its prognostic value. Using the clinical and pathological basis for predicting different outcomes could significantly facilitate SACC stratification and potentially directing treatment.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands

Qian

Kaufmann

Chen

et al. 2016

International Journal of Oncology

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“…Gene expression data (mRNA-seq) and clinical data of 270 head and neck squamous cell carcinomas were obtained from gene expression omnibus (GEO) (http:// www.ncbi.nlm.nih.gov/geo/, accession number:GSE65858) [18]. Clinical data included survival data, gender, age, TNM stage, primary site and HPV status, alcohol, and smoking habit.…”

Section: Gene Expression Data and Clinical Informationmentioning

confidence: 99%

“…Therefore, the objectives of this study were to analyze the expression pattern of ALDH2 and SOD2 genes using available microarray data (GSE65858 and GSE39368) [18] and determine the relationship between the expression level of these two genes and clinical parameters such as alcohol drinking, tobacco smoking, primary site of HNSCC, and human papilloma virus (HPV) state.…”

Section: Introductionmentioning

confidence: 99%

Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma

Lee

Kim

et al. 2017

World J Surg Onc

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Background: This study aims to determine the relationship between expression levels of ALDH2 and SOD2 genes and clinical parameters such as alcohol drinking, tobacco smoking, primary site of HNSCC, and human papilloma virus (HPV) state. Methods: Gene expression data were obtained from gene expression omnibus (GEO accession number: GSE65858). Clinical data (N = 270) including survival result, gender, age, TNM stage, primary site of HNSCC, HPV status, alcohol drinking, and tobacco smoking habit were analyzed according to gene expression pattern. Results: ALDH2 gene was expressed in low levels in patients with heavy alcohol consumption. It was expressed in high (p = 0.01) levels in patients with no or light alcohol consumption. ALDH2 gene was also expressed in low levels in patients with oral cavity cancers or hypopharynx cancers. However, ALDH2 gene was expressed in high (p = 0.03) levels in patients with oropharyngeal cancers or laryngeal cancers. HPV-positive patients were found to have high (p = 0.02) expression levels of ALDH2. SOD2 gene was expressed in high (p = 0.005) levels in patients who had greater mean pack-year of tobacco smoking. Based on log rank test, the group of patients with high expression of ALDH2 showed better (p = 0.002) clinical results than those with low expression of ALDH2. Difference of survival results between ALDH2 high-expressed group and ALDH2 low-expressed group was validated in another cohort (GSE39368, N = 138). Conclusions: Heavy alcohol drinking downregulates ALDH2 gene expression level. Heavy smoking up-regulates SOD2 gene expression level in patients with head and neck squamous cell carcinoma. The group of patients with low expression levels of ALDH2 showed significantly poorer survival results compared to those with high expression levels of ALDH2.

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“…Some studies have described differences between HPVpositive and HPV-negative OPSCC with regard to RNA expression and differences have mainly been reported in genes involved in immune response, apoptosis, proliferation/ cell cycle and differentiation (74)(75)(76)(77)106). Notably, some studies have, based on transcriptional and HPV data, suggested molecular sub-grouping of HNSCC.…”

Section: Transcriptome Analysis In Opsccmentioning

confidence: 99%

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Näsman

Bersani

Lindquist

et al. 2017

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Abstract. Human papillomavirus (HPV)-positive tonsillarand base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negativeIn 2007, human papillomavirus (HPV) was recognized as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC) by the International Agency for Research against Cancer (IARC), besides the traditional risk factors smoking and alcohol (1-4). Concurrently, an increased incidence of OPSCC, more specifically tonsillar and base of tongue cancer (TSCC and BOTSCC, the two main HPV-positive OPSCC sites) was described in many developed countries, and found to be due to a sharp rise of HPV-positive cases (5-18). These HPV-positive tumors had a much better clinical outcome than their HPV-negative counterparts and head and neck squamous cell carcinoma (HNSCC) in general when treated with radiotherapy and surgery (1-3, 15-17, 19, 20). Treatment of HNSCC including OPSCC has, however, gradually become more intensified with induction chemotherapy or concurrent chemo-radiotherapy and sometimes the administration of Erbitux, leading to more severe side effects (16, 20, 21). This is likely unnecessary for most HPV-positive TSCC and BOTSCC patients since they generally respond well to less therapy and furthermore, intensified therapy does not improve survival of [15][16][17] 20, 22, 23). It is, therefore, important to identify patients with HPV-positive TSCC and BOTSCC eligible for less treatment or targeted therapy and efforts focus now on finding predictive and targetable markers for these patients (24-39).Here, a short background of the field and an update on recent attempts to find predictive and targetable markers with different methodologies for individualized therapy is presented. Human Papillomavirus in Tonsillar and Base of Tongue Squamous Cell Carcinoma and an Epidemic Increase of these TumorsIn 2000, an association between HPV and OPSCC and TSCC was reported, and with radiotherapy and surgery, these HPVpositive cases had much better outcome than corresponding HPV-negative cases (80% vs. 40-50% 5-year survival) (1, 2). In 2004, a similar relationship of HPV to BOTSCC, but not to mobile tongue cancer was disclosed (40). Based on 5319

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The role of HPV RNA transcription, immune response‐related gene expression and disruptiveTP53mutations in diagnostic and prognostic profiling of head and neck cancer

Cited by 198 publications

References 44 publications

Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands

Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands

Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

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