Abstract
To explore the correlation of human papillomavious (HPV) infection with expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. 166 biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20 laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerase chain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed using immunohistostaining. The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3%) than in LP (6.3%) (P<0.0005). Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV 16/18 coinfection than those of Uygur and Kazak ethnicity (P<0.05). Overexpression of p53 and PCNA were higher in LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P<0.005, and P<0.005, respectively). That of p53 was not associated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated with clinical stage. These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC and LP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpression of p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation in HPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.
Highlights
Laryngeal cancer is one of the most common head and neck malignancy, and approximately 159,000 new cases are diagnosed annually worldwide (Parkin et al, 2005; Marioni et al, 2006; Marur and Forastiere, 2008)
The frequency of human papillomavious (HPV) infection varied with the subtypes of HPV in laryngeal carcinomas, appaloosas, and polyps was showed in Table 1, HPV 6/11 were detected in 21/63 (33.3%) of the laryngeal papillomas (LP), 8/83(9.6%) of the laryngeal squamous cell carcinomas (LSCC), and none of the 20 laryngeal inflammatory polyps (LIP) (P
Evidence have suggested that high risk HPV subtypes 16 and 18 are associated mainly with laryngeal carcinoma whereas low risk HPV subtypes 6 and 11 correlated usually with laryngeal papillomas, and HPV 30 and 33 have been detected in a few laryngeal carcinomas
Summary
Laryngeal cancer is one of the most common head and neck malignancy, and approximately 159,000 new cases are diagnosed annually worldwide (Parkin et al, 2005; Marioni et al, 2006; Marur and Forastiere, 2008). Squamous cell carcinoma represents most of laryngeal cancer, accounting for more than 95% of primary laryngeal tumors, and is more common in males (sex ratio 7:1) (Parkin et al, 2005; Ji et al, 2008). Despite efforts over the last 20 years in laryngeal squamous cell carcinoma (LSCC) have been made, and some factors such as smoking, alcohol, occupational, and environmental factors have been implicated as important etiologic agents in the pathogenesis of LSCC, the complex pathogenesis is still unclear and the clinical prognosis remains poor (Parkin et al, 2001; Marioni et al, 2006). HPVE6 and E7 are able to induce the degradation of p53 by binding to the ubiquitin ligase E6AP, inhibiting p53-dependent signaling upon stress stimuli, and contributing to LSCC development (Pruneri et al, 1997; Du et al, 2003)
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