Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma
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Background: Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We ex-amined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC. Methods: Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV. Results: Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1). Conclusions: Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.
Abstract
Background: Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We ex-amined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC. Methods: Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV. Results: Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1). Conclusions: Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.
참고문헌 (30)
- Chaturvedi AK, "Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States", J Clin Oncol, 26, pp.612~619 (2008)
- Adelstein DJ, "Head and neck squamous cell cancer and the human papillomavirus", Head Neck, 31, pp.1393~1422 (2009)
- Ragin CC, "Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis", Int J Cancer, 121, pp.1813~1820 (2007)
- D’Souza G, "Case-control study of human papillomavirus and oropharyngeal cancer", N Engl J Med, 356, pp.1944~1956 (2007)
- Kumar B, "EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer", J Clin Oncol, 26, pp.3128~3137 (2008)
- Adelstein DJ, "Concurrent chemoradiotherapy in the management of squamous cell cancer of the oropharynx: current standards and future directions", Int J Radiat Oncol Biol Phys, 69(2 Suppl), pp.37~39 (2007)
- Hafkamp HC, "A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16", 18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5-8, 2003, pp.107, 394~400
- Klussmann JP, "Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus", Am J Pathol, 162, pp.747~753 (2003)
- Sherr CJ, "The RB and p53 pathways in cancer", Cancer Cell, 2, pp.103~112 (2002)
- Mendolsohn J, "The molecular basis of cancer. 2nd ed", pp.41~ (2001), W. B. Saunders
- Kumar V, "Robbins and Cotran pathologic basis of disease. 8th ed", pp.290~ (2010), Saunders
- Karam JA, "Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy", Lancet Oncol, 8, pp.128~136 (2007)
- Dean E, "Phase I trial of AEG35156 administered as a 7-day and 3-day continuous intravenous infusion in patients with advanced refractory cancer", J Clin Oncol, 27, pp.1660~1666 (2009)
- Jäckel MC, "Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of bcl-2 and bax protein expression", Cancer, 85, pp.591~599 (1999)
- Erber R, "Aberrant p21(CIP1", WAF1) protein accumulation in head-and-neck cancer, 1997, pp.74, 383~389
- Lewis JS Jr, "p16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status", Am J Surg Pathol, 34, pp.1088~1096 (2010)
- Lassen P, "Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck", J Clin Oncol, 27, pp.1992~1998 (2009)
- Braakhuis BJ, "Human papillomavirus in head and neck cancer: the need for a standardised assay to assess the full clinical importance", Eur J Cancer, 45, pp.2935~2939 (2009)
- Schache AG, "Evaluation of human papillomavirus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination", Clin Cancer Res, 17, pp.6262~6271 (2011)
- Wiest T, "Involvement of intact HPV16 E6", E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control, 2002, pp.21, 1510~1517
- Peltenburg LT, "Radiosensitivity of tumor cells: oncogenes and apoptosis", Q J Nucl Med, 44, pp.355~364 (2000)
- Robinson M, "Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing", Oral Oncol, 46, pp.492~496 (2010)
- Smeets SJ, "A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen", Int J Cancer, 121, pp.2465~2472 (2007)
- Rischin D, "Prognostic significance of HPV and p16 status in patients with oropharyngeal cancer treated on a large international phase III trial", J Clin Oncol, 27(15s) (2009)
- Andl T, "Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control", Cancer Res, 58, pp.5~13 (1998)
- Sampaio-Góes FC, "Expression of PCNA, p53, Bax, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis", Head Neck, 27, pp.982~989 (2005)
- Lo Muzio L, "Bcl-2 as prognostic factor in head and neck squamous cell carcinoma", Oncol Res, 15, pp.249~255 (2005)
- Popović B, "Bcl-2 expression in oral squamous cell carcinoma", Ann N Y Acad Sci, 1095, pp.19~25 (2007)
- Nichols AC, "Bcl2 and human papillomavirus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer", Clin Cancer Res, 16, pp.2138~2146 (2010)
- Loro LL, "Loss of BCL-2 in the progression of oral cancer is not attributable to mutations", J Clin Pathol, 58, pp.1157~1162 (2005)
