The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two assays are technically easier to perform; hence, HPV16 ISH or p16 IHC should become standard evaluations for all patients with OSCC.

Background: The incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) have risen steadily in the USA and in northern Europe. These increases are thought to be a consequence of persistent infection with high-risk human papillomavirus (HPV) in OPSCC patients. HPV is an emerging etiologic factor in OPSCC. In Japan, the incidence of OPSCC has significantly increased over the last three decades. However, the population of HPV-positive OPSCC patients is currently unknown. We examined the nationwide trends with regard to HPV incidence in OPSCC patients at 21 specific sites, and examined the relationship between the presence of HPV and survival in OPSCC patients in Japan. Methods: Tumor samples were obtained from patients with OPSCC prior to treatment, and HPV infection was investigated by polymerase chain reaction (PCR). Hybrid Capture 2 (HC2) was also adopted for swab examination on the surface of fresh tumors. Results: HPV was detected by PCR in 79 (50.3%) out of 157 OPSCC patients. The clinical features of HPV-positive OPSCC were low differentiation, a tendency to involve the lateral wall, and high nodal staging. The sensitivity and specificity of HC2 were 93.7 and 96.2%, respectively, indicating its utility as a screening test. HPV-positive patients had significantly better overall survival and disease-free survival than HPV-negative patients.

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Purpose: Rapidly metabolizing tumor cells have elevated levels of nicotinamide phosphoribosyltransferase, an enzyme involved in NAD + biosynthesis, which serves as an important substrate for proteins involved in DNA repair. GMX1777, which inhibits nicotinamide phosphoribosyltransferase, was evaluated in two human head and neck cancer models in combination with radiotherapy. Experimental Design: Effects of GMX1777-mediated radiosensitization were examined via metabolic and cytotoxicity assays in vitro; mechanism of action, in vivo antitumor efficacy, and radiosensitization were also investigated.Results: IC 50 values of GMX1777 for FaDu and C666-1 cells were 10 and 5 nmol/L, respectively, which interacted synergistically with radiotherapy. GMX1777 induced a rapid decline in intracellular NAD + followed by ATP reduction associated with significant cytotoxicity. These metabolic changes were slightly increased with the addition of radiotherapy, although poly(ADP-ribose) polymerase activity was significantly reduced when GMX1777 was combined with radiotherapy, thereby accounting for the synergistic cytotoxicity of these two modalities. Systemic GMX1777 administration with local tumor radiotherapy caused complete disappearance of FaDu and C666-1 tumors for 50 and 20 days, respectively. There was also significant reduction in tumor vascularity, particularly for the more sensitive FaDu model. Conclusions: Our data represent the first report showing that GMX1777 plus radiotherapy is an effective therapeutic strategy for head and neck cancer, mediated via pleiotropic effects of inhibition of DNA repair and tumor angiogenesis, while sparing normal tissues. Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients. Clin Cancer Res; 16(3); 898-911. ©2010 AACR.Head and neck cancer is the fifth most common neoplasm worldwide (1, 2), with an estimated 644,000 new cases diagnosed each year wherein 60% of such patients present with stage III or IV disease (1, 2). Such locally advanced head and neck squamous cell cancers are treated with either hyperfractionated radiotherapy (3) or chemoradiotherapy (1, 2) but still associated with >50% mortality rate (1, 2), underscoring an urgent need to develop novel molecular therapies.Cancer cells have a dysregulated metabolism, which provides a survival advantage despite a noxious environment (4, 5). Consequently, there is increased demand for energy consumption and DNA repair. One of the key cofactors in cellular respiration is NAD + , which plays several essential roles, including serving as a coenzyme in redox reactions, providing substrates for the poly(ADP-ribose) polymerase (PARP), and sirtuins (6), a newly described group of proteins involved in multiple functions including DNA repair that requires NAD + to deacetylate (7). All these processes are involved in stress response, genomic instability, and apoptosis. In the mammalian system, the three major precursors of NAD + synthesis are tryptophan, nicotinic acid...

Background Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de‐escalating treatment modality has not been established to date. Methods The authors conducted a retrospective, nationwide, observational study in patients with HPV‐related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. Results A total of 688 patients who were newly diagnosed with HPV‐related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow‐up data available were included in the current study. In patients with T1‐T2N0 disease (79 patients), both the 3‐year recurrence‐free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3‐year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV‐related OPSCC, the 5‐year recurrence‐free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high‐dose cisplatin (≥160 mg/m2; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low‐dose cisplatin (<160 mg/m2; 17 patients). Conclusions Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1‐T2N0 HPV‐related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV‐related OPSCC other than those with T1‐T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2.

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A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA.

A rare case of second branchial fistula with heterotopic salivary gland tissue in the lower neck is described. The patient was a 12-year-old girl with a fistula which appeared to be clinically a second branchial cleft anomaly. It was removed from her neck. Histological examination revealed that the lesion was a branchial cleft fistula with elements of salivary gland tissue.