Head and Neck Cancer

Forastiere, Arlene A.; Koch, Wayne M.; Trotti, A.; Sidransky, David

doi:10.1056/nejmra001375

Cited by 1,190 publications

(926 citation statements)

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“…For instance, in addition to differences in HPV involvement of separate anatomic sites, with common involvement of the oropharynx, it is becoming apparent that HPV related carcinomas have an improved outcome compared to HPV negative carcinomas when adjusted for anatomic site and clinicopathologic stage [7,8]. Additionally, the heterogeneity of oncogene alteration among head and neck tumors supports such differences [9]. Differences in immune host response, tumor adhesion properties, invasiveness modulators, are possible pathways that may differ with tumor anatomic site.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

Belbin

Smith

Adrien

et al. 2008

Head and Neck Pathol

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It is known that head and neck squamous cell carcinomas (HNSCC) originating from different anatomic locations can exhibit varying behavior that is not predictable by histopathology of the primary tumor. Using a microarray containing 27,323 cDNA clones, we generated sets of gene expression profiles for 36 HNSCC primary tumors (12 oral cavity, 12 oropharynx, and 12 larynx/ hypopharynx). From these datasets, we ranked genes according to their ability to differentiate between patients whose disease progressed within a 24 month period (aggressive phenotype) and those that did not (nonaggressive phenotype) based on levels of gene expression. A merging of datasets from the three sites revealed that only a fraction of identified genes were shared between any two sites. This contrasted greatly with the significant overlap (approximately 50%) in down-regulated genes identified in tumor/normal comparisons using cases both from oropharynx and larynx/hypopharynx. From these data, we conclude that HNSCC tumors originating from different anatomic sites share consistent changes in gene expression when comparing primary tumors to normal adjacent mucosa; these common changes most likely reflect alterations required for tumor development. In contrast, once a tumor has developed, tumor-host interactions at the different anatomic sites are likely responsible for the site-specific signatures associated with aggressive versus non-aggressive disease. Predictions of outcome based on gene expression profiling are therefore heavily influenced by the anatomic site of the primary tumor.

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Section: Introductionmentioning

confidence: 99%

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

Belbin

Smith

Adrien

et al. 2008

Head and Neck Pathol

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“…3 Well-recognized risk factors in the etiology of head-and-neck squamous cell carcinomas are extensive tobacco and alcohol consumption in B90% of cases, as well as oncogenic human papillomaviruses (HPVs), predominantly HPV type 16. 3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8] …”

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confidence: 99%

“…9 It has been shown that there are several differences between HPV-positive and -negative headand-neck squamous cell carcinomas. Despite the fact that HPV positivity in head-and-neck squamous cell carcinomas is an indicator for favorable prognosis, from a clinical point of view these tumors are often poorly differentiated 4,6,[10][11][12] and metastasized to lymph nodes at presentation. 10,11 Furthermore, HPV-positive tumors are often smaller at first diagnosis (diameter r4 cm), 13 and associated with low/no exposure to alcohol and tobacco.…”

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confidence: 99%

P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis

et al. 2009

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Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16 INK4A, cyclin D1, pRb, p14 ARF , MDM2, p53, p21 Cip1/WAF1 , and p27 KIP1 . Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16 INK4A overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14 ARF (Po0.0001) and p21 Cip1/WAF1 (P ¼ 0.001), and downregulation of pRb (Po0.0001) and cyclin D1 (P ¼ 0.027) compared with the human papillomavirus-negative cases. Univariate Cox regression analyses revealed a favorable survival rate for non-smokers (P ¼ 0.006), as well as for patients with T1-2 tumors (Po0.0001) or tumors showing low expression of cyclin D1 (P ¼ 0.028), presence of human papillomavirus and overexpression of p16 INK4A (P ¼ 0.01), p14 ARF (P ¼ 0.02) or p21 Cip1/WAF1 (P ¼ 0.004). In multivariate regression analyses, smoking and tumor size, as well as expression of cyclin D1 and p21 Cip1/WAF1 , were found to be independent prognostic markers. We conclude that human papillomavirus positivity in tonsillar squamous cell carcinomas strongly correlates with p21 Cip1/WAF1 and p14 ARF overexpression and downregulation of pRb and cyclin D1. In particular p21 Cip1/WAF1 overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas. Modern Pathology ( Head-and-neck squamous cell carcinoma is the sixth most prevalent malignancy in the world, contributing 6% of new cancer cases annually worldwide. 1,2 These tumors have a 5-year survival rate of approximately 50%, which has not improved in the last two decades. 3 Well-recognized risk factors in the etiology of head-and-neck squamous cell carcinomas are extensive tobacco and alcohol consumption in B90% of cases, as well as oncogenic human papillomaviruses (HPVs), predominantly HPV type 16. 3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8]

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“…Despite recent advances in cancer treatment, the 5-year overall survival rate for patients with squamous cell carcinoma of the head and neck (HNSCC) has not improved over the last 30 years (Forastiere et al, 2001;Greenlee et al, 2001). The primary cause of treatment failure in patients with early-stage disease is the development of second primary tumours, whereas patients who present with locally advanced disease are at risk for local -regional recurrence and metastasis, even with the use of near-tolerance doses of radiation (Day and Blot, 1992).…”

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confidence: 99%

Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

et al. 2008

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Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC.

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Head and Neck Cancer

Cited by 1,190 publications

References 84 publications

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis

Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

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