To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.

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 ...

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Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.

Robot-assisted SOND via a modified face-lift or retroauricular approach in cN0 oral cavity SCC was feasible compared to conventional technique and showed a clear cosmetic benefit. Longer operation time remains the drawback of this procedure. However, it could be considered for patients who require SOND and prefer to avoid external neck scar.

These results suggest that elective N0 neck treatment in patients with oropharyngeal SCC, especially base of tongue cancer, should include neck levels II, III, and IV instead of levels I, II, and III.

Despite the weakness of this nonrandomized trial and the differences in T classification, TORS seemed to have distinct advantages over conventional transoral surgery and other conventional open surgery, but further studies are needed.

Although the aspect of invasiveness could be improved, endoscopic hemithyroidectomy via a unilateral axillo-breast approach without gas insufflation is safe and effective and appears to provide better cosmetic results and a shorter operation time than other endoscopic methods for managing selective unilateral benign thyroid lesions.