Molecular Pathogenesis of Human Papillomavirus Type 16 in Tonsillar Squamous Cell Carcinoma.

AIM: The present study aimed to explore the etiological role of human papillomavirus (HPV) in tonsillar squamous cell carcinoma (TSCC). MATERIALS AND METHODS: HPV status, including viral load and E6 variants, and the expression of P53, p16(INK4A), and FANCD2, in tissues of TSCC (n=24) and tonsillitis (n=31) were investigated. RESULTS: The frequency of high-risk HPV (HPV-16) in TSCCs (42%) was higher than that of tonsillitis (16%). HPV-16 genome was partially or fully integrated in all HPV-16-positive TSCCs. However, the viral genome was partially integrated in three out of five HPV-16-positive tonsillitis cases (p=0.037). HPV-16-positive TSCCs showed a higher frequency of p16(INK4A) expression than HPV-16-negative TSCCs and tonsillitis (p=0.011). Regardless of HPV status, TSCCs had a lower expression of FANCD2 than tonsillitis (p=0.008). CONCLUSION: The present study supports the etiological role of HPV-16 in the development of TSCC, and p16(INK4A) overexpression can be applied as a surrogate marker for the detection of high-risk-HPV in TSCC.

Presence of keratin-specific antibody-forming cells in palatine tonsils of patients with pustulosis palmaris et plantaris (PPP) and its correlation with prognosis after tonsillectomy.

CONCLUSION: Keratin-specific immune responses in tonsils may be associated with the pathogenesis of pustulosis palmaris et plantaris (PPP). Evaluation of keratin-specific immune responses in tonsils might be useful to predict the effectiveness of tonsillectomy for patients with PPP. OBJECTIVES: The aim of the present study was to clarify the role of keratin-specific immune responses in the pathogenesis of PPP in tonsils. It has been reported that anti-keratin antibodies in serum were higher in patients with PPP and decreased after tonsillectomy, indicating that anti-keratin antibodies might be generated in tonsils. METHODS: In order to demonstrate the presence of keratin-specific immune responses in tonsils, the numbers of keratin-specific antibody-forming cells (AFCs) in tonsillar and peripheral blood lymphocytes were examined by enzyme-linked immunospot assay. The prognosis of PPP was compared after tonsillectomy. RESULTS: The numbers of keratin-specific IgM and IgG AFCs in tonsils and of IgG AFCs in peripheral blood were significantly increased in patients with PPP. The numbers of keratin-specific IgG AFCs in peripheral blood correlated positively with tonsil and serum IgG antibodies specific to keratin. Our data show that a good prognosis in patients with PPP depended on the numbers of keratin-specific IgG and IgM AFCs in peripheral blood and the levels of keratin-specific IgG antibodies in serum being significantly decreased 6 months after tonsillectomy.

The role of vascular endothelial growth factor in pediatric otitis media with effusion.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis and vascular permeability, and has been shown to play an important role in inflammatory events, together with hypoxia and inflammatory cytokines. VEGF messenger ribonucleic acid (mRNA) is expressed in the middle ear in an experimental animal model of otitis media with effusion (OME) and in patients with OME. However, the protein levels of VEGF in middle ear effusions (MEEs) are unknown and the role of VEGF in the pathogenesis of OME is unclear. The goals of this study were to determine the VEGF levels in MEEs and to investigate the role of VEGF in production of MEEs by comparing these levels with those of interleukin-8 (IL-8), endotoxin, and albumin. METHODS: Forty-six MEEs obtained from 33 children (24 boys, 9 girls) were used in the study. The mean age of the subjects was 6.3 years old (range, 1-12 years old). The patients underwent myringotomy and/or insertion of a ventilation tube for treatment of OME. After myringotomy, MEEs were collected with a Juhn Tym-Tap. The samples were divided into serous and mucoid types based on observation by the naked eye. After measuring the weight of the MEE, the sample was diluted with phosphate-buffered saline and frozen until use. The concentrations of VEGF and IL-8 in the MEEs were determined by enzyme-linked immunosorbent assays, endotoxin concentrations were measured by the Limulus Amebocyte Lysate test, and albumin levels were determined using an immunoturbidimetric assay. RESULTS: VEGF, endotoxin, IL-8, and albumin were detected in 100%, 89%, 98%, and 100% of the 46 MEEs, respectively. The concentrations of VEGF, endotoxin, and IL-8 were significantly higher in mucoid MEEs than in serous MEEs (p<0.01), whereas there was no significant difference in the albumin concentration between mucoid and serous MEEs. The VEGF levels were positively correlated with those of endotoxin (R(2)=0.17, p<0.05) and albumin (R(2)=0.65, p<0.01) in mucoid MEEs, but not in serous MEEs. CONCLUSIONS: Our results suggest that VEGF is produced in response to bacterial components such as endotoxin in the middle ear cavity and is associated with production of mucoid MEEs by increasing serum exudation and mucosal secretion.