The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1a, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p < 0.0001), and an inverse association with EGFR amplification (p 5 0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p 5 0.034) and HIF-1a overexpression (p 5 0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase. ' 2006 Wiley-Liss, Inc.Key words: human papillomavirus; integration; tonsil cancer; p16; epidermal growth factor receptor Human papillomavirus (HPV) may be postulated to play a role in the pathogenesis of palatine tonsillar cancer (TC), not only due to its morphological similarities to cervical cancer but also because the mucosal squamous epithelium, similar to that of the uterine cervix, is easily exposed to viral infection. HPV infection is prevalent in the oropharyngeal mucosal regions, and the tonsil is the most commonly affected anatomical region in the oropharynx.1,2 Furthermore, TC frequently has a verrucous or papillomatous appearance, with tumor cells showing features of HPV infection, namely koilocytotic atypia. However, it remains uncertain whether HPV is directly associated with the malignant transformation of oropharngeal tumors.The molecular biology of viral oncogenesis has been well established. The viral protein E6 promotes the degradation of p53 and E7 inactivates pRb, usually followed by viral integration into the host genome.3,4 For viral integration, disruption occurs most frequently in an E2 open reading frame (ORF), the E1 ORF being disrupted in a minor proportion of patients. Both are important in viral replication and transcription. More specifically, the breakage of E2 allows for the dysregulation of the E6/E7 oncoprotein, which eventually leads to malignant transformation. 5 In the non-integrated episomal state, the transcriptional level of E6/E7 is regulated by a promoter in the long control region in high-risk HPV-infected cells. It is ...

These results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer.

The risk of contralateral occult neck involvement in above T3 staged tonsillar squamous cell carcinomas with unilateral metastases was high (approximately 21%), and patients who present with a contralateral metastatic neck have a worse prognosis than those who are staged as N0. Therefore, we advocate an elective contralateral neck treatment in tonsillar squamous cell carcinoma patients with ipsilateral node metastases.

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