The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil

Li, Wei; Thompson, Carol H.; Cossart, Yvonne E.; O’Brien, Christopher J.; McNeil, Edward; Scolyer, Richard A.; Rose, Barbara

doi:10.1002/hed.10335

Cited by 99 publications

(108 citation statements)

References 29 publications

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“…We noticed that the tumors with the low expression levels of pRb showed the overexpression of p16 INK4A . Accumulation of this latter protein has been strongly associated with the presence of oncogenic HPV in oropharyngeal carcinomas, 7,10,14,15 which was also evident in the underlying study. These HPV16-positive tonsillar squamous cell carcinomas furthermore showed the downregulation of cyclin D1, next to the accumulation of p14 ARF and p21 Cip1/WAF1 .…”

Section: Discussionsupporting

confidence: 65%

“…In our study, p53 overexpression was observed in little more than half of all tonsillar carcinomas, which is consistent with other studies. 7,42 Immunostaining of all other cell cycle proteins was evident in less than 50% of tumors. We noticed that the tumors with the low expression levels of pRb showed the overexpression of p16 INK4A .…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8] …”

mentioning

confidence: 99%

“…3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8] The diagnosis of HPV positivity in head-andneck squamous cell carcinomas appears to have significant prognostic implications. In one study, these patients had o50% chance of dying from the disease compared with HPV-negative tumors.…”

mentioning

confidence: 99%

“…10,11 At the molecular level, the functional inactivation of two key tumor suppressor proteins, ie, p53 and pRb by the HPV-derived oncoproteins E6 and E7, often result in the downregulation of p53, pRb, cyclin D1, and a strong upregulation of p16 INK4A in HPVpositive tumors. 5,7,[14][15][16] HPV-negative tumors, in contrast, often show inactivation of p16 INK4A , p53 overexpression as a result of gene mutations, cyclin D1 gene amplification and overexpression, as well as EGFR accumulation. 3,[17][18][19] The literature, however, shows conflicting data with respect to HPV-associated characteristics and clinical outcome of head-and-neck squamous cell carcinomas.…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

“…3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8] …”

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

et al. 2009

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Effects of polyhedral oligomeric silsesquioxane coatings on the interface and impact properties of carbon‐fiber/polyarylacetylene composites

Zhang

Huang

Wang

et al. 2006

J of Applied Polymer Sci

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Two kinds of polyhedral oligomeric silsesquioxane (POSS) coatings were used for the modification of the interface in carbon fiber (CF) reinforced polyarylacetylene (PAA) matrix composites. The effects of the organic-inorganic hybrid POSS coatings on the properties of the composites were studied with short-beam-bending, microdebonding, and impact tests. The interlaminar shear strength and interfacial shear strength showed that the POSS coatings resulted in an interfacial property improvement for the CF/PAA composites in comparison with the untreated ones. The impact-test results implied that the impact properties of the POSS-coating-treated composites were improved. The stiffness of the interface created by the POSS coatings was larger than that of the fiber and matrix in the CF/PAA composites according to the forcemodulation-mode atomic force microscopy test results. The rigid POSS interlayer in the composites enhanced the interfacial mechanical properties with a simultaneous improvement of the impact properties; this was an interesting phenomenon in the composite-interface modification.

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Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

et al. 2013

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Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074–0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

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The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil

Cited by 99 publications

References 29 publications

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

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

Effects of polyhedral oligomeric silsesquioxane coatings on the interface and impact properties of carbon‐fiber/polyarylacetylene composites

Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

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