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Abstract: Malignant basaloid neoplasms of the skin are frequent, and their accurate diagnosis holds paramount importance for treatment and prognosis. However, these neoplasms can present diagnostic challenges because of their extensive differential diagnosis, which encompasses cutaneous metastasis among many other possibilities. We present a case of a 74-year-old man with a history of p16-positive palatine tonsil squamous cell carcinoma (SCC) treated with surgery and adjuvant radiation with no prior evidence of recurrence who presented to the dermatologist with 2 chin papules. The initial histopathologic evaluation of these lesions showed poorly differentiated malignant basaloid neoplasms. Subsequently, these biopsies were compared with the previous biopsies from his tonsil and lymph node, which showed similar findings including positive p16 staining and positive molecular testing for human papillomavirus-16, confirming the diagnosis of cutaneous metastasis from his previously diagnosed human papillomavirus-related tonsil SCC. Additional imaging studies found metastases to internal organs including the brain, and he was started on chemotherapy, immunotherapy, and radiation therapy. Cutaneous metastases from tonsil SCC are exceedingly rare, and only 5 cases have been described. Furthermore, this is the first case confirming the presence of high-risk human papillomavirus by molecular studies within the cutaneous metastases. The presented case underscores the importance of recognizing this unusual manifestation of tonsil SCC metastatic to the skin along with a good clinical patient history, ensuring accurate and prompt diagnosis and treatment of this condition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16 INK4a undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval( CI ): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95% CI : 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95% CI : 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95% CI : 0.51-1.40; DSS: aHR: 0.62, 95% CI : 0.35-1.11; DFS: aHR: 0.80, 95% CI : 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

Background: This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT)., Methods: CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients., Results: The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems., Conclusion: One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients., (© 2021 Wiley Periodicals LLC.)

Objective: To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status., Study Design: Historical cohort study., Setting: National Cancer Database (NCDB)., Methods: Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed., Results: A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%, P < .001). Among HPV-positive patients, there was no significant difference in survival between treatment cohorts. However, in the HPV-negative cohort, 3-year survival was higher in both bimodality surgical-based settings (tonsillectomy + neck dissection + radiotherapy, 86.0% vs chemoradiotherapy, 69.6%, P = .01) and for all surgical-based treatments when compared to nonsurgical management (84.6% vs 69.3%, P < .001). This difference was maintained in multivariable regression controlling for age, sex, comorbidities, clinical T stage, and treatments. In a subpopulation of HPV-negative patients propensity score matched by all factors significant in multivariable analysis, 3-year survival remained higher in the surgically treated group compared to the nonsurgically treated cohort (84.9% vs 67.1%, P < .001)., Conclusions: Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.

The incidence of Human-papillomavirus-positive (HPV + ) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV - ) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV + TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

Objective: Compared with Occident's data, the incidence of Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) had been reported as relatively low in Mainland China. The objective of this study was to report the integrated prevalence of HPV and Epstein-Barr virus (EBV), and further evaluate the different behaviors of HPV-positive and -negative OPSCCs in eastern China., Methods: In a cohort of 170 nonmetastatic OPSCCs treated from January 2007 to July 2019, p16 protein expression, HPV genotypes, and Epstein-Barr virus-encoded RNA (EBER) were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). The clinical and pathologic findings were further collected and analyzed to comprehensively reveal the behaviors of Chinese OPSCCs., Results: Out of the 170 tumor tissues evaluated, 57.6% (98) samples had positive p16 expressions. A total of 65.1% (99/152) samples had positive HPV genotypes, besides HPV16 (92/152), HPV11, 18, 33, 53, and 58 were also detected. The positive rate of EBER was 7.2% (9/124), and the co-infection rate of EBV/HPV was 4.0%. Related to the unequal distributions of p16 expression, HPV-related tumors arisen from tonsillar and non-tonsillar accounted for 68.8% (75/109) and 37.7% (23/61) of their cases, respectively (P < .001). With a median follow-up time of 13.1 months, significant survival advantages of HPV-related OSPCC were observed; 1-year OS, PFS, RFS, and MFS were 83.2% vs 96.7% (P < .001), 71.6% vs 96.2% (P < .001), 77.7% vs 96.2% (P = .002), and 90.4% vs 100.0% (P = .024) in p16-negative and -positive cases, respectively., Conclusions: The relative percent of HPV-positive OPSCCs in this study is close to the positive rate in many Western countries and a strong predilection was discovered for the tonsillar. The EBV infection and co-infection of HPV/EBV were largely low. The prognosis of HPV-positive OSPCCs was more favorable than its negative counterpart., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This study aimed to establish and validate a comprehensive nomogram for predicting the cause-specific survival (CSS) probability in tonsillar squamous cell carcinoma (TSCC). We screened and extracted data from the SEER (Surveillance, Epidemiology, and End Results) database for the period 2004 to 2016. We randomly divided the 7243 identified patients into a training cohort (70%) for constructing the model and a validation cohort (30%) for evaluating the model using R software. Multivariate Cox stepwise regression was used to select predictive variables. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the model. The multivariate Cox stepwise regression analysis successfully established a nomogram for the 1-, 3-, and 5-year CSS probabilities for TSCC patients. The C-index, AUC, NRI, and IDI were all showed that the model has good discrimination. The calibration plots were very close to the standard lines, indicating that the model has a good degree of calibration, and the DCA curve further illustrated that the model has good clinical validity. We have established the first nomogram for predicting the 1-, 3-, and 5-year CSS probabilities for TSCC based on a large retrospective sample. Our rigorous validation and evaluation indicated that the model can provide useful guidance to clinical workers making clinical decisions about individual patients.

Tonsillar synovial sarcoma is an extremely rare entity and only 9 adult patients have been reported up to now. Here, we describe the first pediatric tonsillar synovial sarcoma of the literature in a patient who presented with a 2-month history of dysphagia and snoring. Clinical and radiological examinations showed that the tumor arose from the right palatine tonsil and narrowed the parapharyngeal space. An incisional biopsy from the palatine tonsil revealed the diagnosis of synovial sarcoma. The patient has underwent total tonsillectomy and received radiotherapy and chemotherapy because of the positive surgical margins. The patient is clinically in good condition and free of tumor 30 months after the initial diagnosis. We achieved a long-term complete remission with a combination of surgery, radiotherapy and chemotherapy in our case. Tonsillar synovial sarcoma should be kept in mind while dealing with tonsillar masses. We can conclude that a multidisciplinary approach is warranted while treating synovial sarcoma with this localization.

Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment., Methods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting., Findings: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS., Interpretation: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options., Funding: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Treatment of the uninvolved neck in well-lateralized tonsillar squamous cell carcinoma is controversial. We became concerned after a number of contralateral neck recurrences (CNRs) in patients receiving ipsilateral radiotherapy (RT)., Methods: This is a single center retrospective series including patients with well-lateralized tonsillar cancer treated with ipsilateral neck RT between 2004 and 2011., Results: We identified 53 patients treated with ipsilateral neck RT during the study period. The rate of CNR was 7.5% (4 of 53). All four patients had p16-positive, T1, N2b, M0 tumors. The subgroup of patients with N2b disease (28 of 53) had a CNR of 14.3%. We subsequently switched to treat patients with N2b with bilateral neck RT. We analyzed the outcomes of 23 patients with N2b treated with bilateral neck intensity-modulated RT (IMRT) and observed no CNRs., Conclusions: We observed a higher than expected rate of CNR in the N2b population. Bilateral neck IMRT for these patients represents a safe alternative., (© 2019 Wiley Periodicals, Inc.)

Background: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development., Methods: Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed., Results: After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab., Conclusions: We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development.

Objective: To examine the survival of pediatric tonsillar cancer patients and review a rare case of pediatric tonsillar cancer., Methods: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of tonsillar malignancy using the ICD O-3 tonsil primary site codes of: C09.0, C09.1, C09.8, and C09.9. Patients were included from birth-18 years. Survival analysis was performed using Kaplan-Meier analysis. Additionally, a case of pediatric natural killer (NK) cell tonsillar lymphoma diagnosed and treated at the Nemours Children's hospital in Orlando, Florida is presented., Results: One hundred forty-one cases of tonsil cancer were identified. The mean age at diagnosis was 9.9 years (SD: 5.1, range: 0.0 (months)-18.0). Ninety five (67.4%) patients were male and 116 (82.3%) had unilateral malignancies. Burkitt lymphoma (32.6%) followed by diffuse large B-cell lymphoma (DLBCL) (27.0%) were the two most common histological types of tonsillar cancers. 79.4% of patients received chemotherapy and 81.6% received surgery as a part of their care. The 5-year disease-specific survival rate was >90% for patient cohorts diagnosed from 1984 to 1993, 1994-2003, and 2004-2014 as compared to 64% for patients diagnosed from 1973 to 1983 (p = 0.01)., Conclusions: Survival rates for pediatric patients with tonsillar cancer are excellent. Pediatric primary tonsil cancer occurred most commonly in adolescent males and usually presents as a unilateral mass. Lymphoma remains the predominant histological type of cancer. Most patients are likely to receive surgery and chemotherapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rationale: Extranodal natural killer T-cell lymphoma nasal type (ENKL) is an extremely rare tumor with a very low survival rate. In recent decades, only a few ENKL cases have been published. Presenting a special ENKL case lead the authors to emphasize the primary features of ENKL in early diagnosis and therapy. Here we report an unusual ENKL case which was initially found in the eyes and presented as masqueraded uveitis PATIENT CONCERNS:: A 55 years old female, with vision loss in the right eye for approximately 6 months, and vision blurry, redness and pain in the left eye for 2 weeks, was referred to our hospital., Diagnosis: Clinical examinations and images demonstrated bilateral anterior uveitis, retinal and choroidal detachment, and secondary glaucoma. After 3 months, the patient began to present a sore throat, fever, and headaches. The computed tomography (CT) and magnetic resonance imaging (MRI) of her skull demonstrated nothing positive. One month later, a neoplasm was found in her nasopharynx and tonsil, which was confirmed, by histopathology, as ENKL INTERVENTIONS:: This patient was prescribed with steroid for 3 months because of the first diagnosis by the ophthalmologist. After the other symptoms like a sore throat, fever and headaches occurred, symptomatic treatment was given. Unfortunately, when the real cause was found, the patient could not tolerate the other treatment for ENKL., Outcomes: Since the patient was treated with steroid without improvement, she died due to the septic shock and multiple organ failure., Lessons: Clinicians should always be cautious to ENKL which can be easily be misdiagnosed in the early stage. Early diagnosis and appropriate treatment are keys to raise the survival rate of ENKL patients.

Competing Interests: None

Chronic lymphocytic leukemia (CLL) patients are at an increased risk for developing more aggressive lymphomas via Richter's transformation and of developing secondary malignancies. Despite the known association for secondary cancers, oropharyngeal cancers occur rarely. We present a case of a woman with a history of CLL who presented to our facility via transfer for impending airway compromise. Her initial workup was consistent with CLL; however, biopsies were taken of the neck mass because of its aggressive nature. She was treated with rituximab with good response. Final pathology showed evidence of CLL and tonsillar squamous cell carcinoma (SCC). Direct laryngoscopy and further biopsies yielded a diagnosis of unresectable oropharyngeal SCC. She was to be treated with chemotherapy and radiation for her SCC while holding treatment for CLL. This case demonstrates a rare and unexpected concurrent diagnosis.

Objective: To evaluate radiation-induced lymphopenia associated with unilateral vs. bilateral neck radiation and to test post-treatment neutrophil to lymphocyte ratio (NLR) as a prognostic clinical biomarker., Methods: This was a single academic center retrospective review of palatine tonsil squamous cell cancer patients treated with post-operative intensity modulated radiation therapy (IMRT) from 1997 to 2013. Absolute lymphocyte count (ALC) and NLR were evaluated during and after radiation for up to a year. Correlations of lab values with loco-regional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were assessed., Results: Ninety-nine patients with median follow up 5.8 years had ALC recorded at least at baseline and within one year of starting RT. Acute grade 3-4 lymphopenia (<10 weeks from RT start) occurred in 79% of bilateral neck RT patients (n = 70) and 58% of unilateral neck RT patients (n = 29), p = 0.03. There was no significant difference in late grade 3-4 (p = 0.12) lymphopenia. In a multivariable Cox regression model, acute NLR > 11.875 correlated with worse OS (HR = 4.4, 95% CI 1.2-16). Late NLR > 6.875 independently correlated with significantly worse FFDM (HR = 16, 95% CI 1.9-137) and OS (HR = 12, 95% CI 3.0-48)., Conclusions: Unilateral neck radiation may prevent acute iatrogenic immunosuppression. In exploratory analyses, elevated post-treatment NLR was associated with risk for distant metastases and death., (Copyright © 2018. Published by Elsevier Ltd.)

Canine non-tonsillar oral squamous cell carcinoma (OSCC) is generally regarded as locally invasive with low rates of metastasis. Two cases of canine non-tonsillar OSCC with occult tonsillar squamous cell carcinoma (TSCC) detected with tonsillar biopsies are reported. Tonsillar biopsies and detection of occult TSCC changed the therapeutic plan and may have contributed to long-term tumor control.

Osteonecrosis of the jaw is a significant complication secondary to radiation therapy or drug therapy, most commonly bisphosphonates. Safety data regarding the administration of bisphosphonates in bone metastatic head and neck cancer patients with history of jaw irradiation are almost non-existent. In this paper, we report the case of a Head and Neck (HNC) patient, with history of radiation therapy to the mandible region, treated with intravenous bisphosphonates for bone metastases that resulted in gross, life threatening mouth hemorrhage secondary to advanced, locally invasive ONJ.

Purpose: To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer., Methods and Materials: Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m 2 , and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m 2 , every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale., Results: Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m 2 ) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m 2 vs 22.3 kg/m 2 ; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up., Conclusions: De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hypopharyngeal and cervical esophageal strictures can be caused by advanced malignancies, ingestion of caustic materials, or can follow surgery or radiation therapy. They cause marked dysphagia and consequently patients need nasogastric or gastrostomy tube feeding, with a remarkable impact on quality of life. To restore oral feeding, the stenosis can be progressively dilated by using rubber bougies of increasing diameter, and a Montgomery ® Salivary Bypass Tube can then be inserted to maintain the obtained calibre. However, while its flexibility makes it easy to tolerate, it has the drawback of making insertion difficult because the tube tends to bend. The aim of this paper is to present a possible solution to this problem. A Montgomery ® Salivary Bypass Tube was distally sutured to a Cook Airway Exchange Catheter ® to simplify its initial insertion through a laryngoscope and following replacements. The catheter was then easily removed leaving the bypass tube in the correct position. In our experience, this innovative approach proved effective in facilitating Montgomery ® Salivary Bypass Tube insertion in three patients, without risks for the patient, additional operative time or increase in costs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Rationale: Lung cancer has the highest mortality of all malignant tumors and is becoming the leading cause of death in China. Surgical resection is the best treatment for early non-small-cell lung carcinoma. But postoperative tumor recurrence is very common. Brain, bone and liver are the most common metastatic sites of lung cancer., Patient Concerns: A 59-year-old woman was admitted to our hospital finding a lung nodule in physical examination. No other obvious symptoms were obsessed in this patient. No remarkable abnormality was detected in preoperative laboratory tests and physical examination., Diagnoses: A ground-glass nodule was detected on the left inferior lobe in the imaging examination. No metastases were detected before the surgery and early-stage lung cancer was supposed., Intervention: This patient underwent a radical resection of lung cancer successfully and enjoyed a peaceful postoperative rehabilitation., Outcomes: Although pathological diagnosed confirmed early stage lung adenocarcinoma (T1N0M0). The patient had tumor recurrence 7 months after operation. Gene sequencing confirmed the G719S mutation in exon 18 of the EGFR gene and target therapy, chemotherapy and radiotherapy were all given to this patient successively, but they were all unresponsive. The patient died 26 months after surgery., Lessons: We herein first report G719S mutation in lung adenocarcinoma with tonsillar metastasis. Generally, the tumor responded poorly to treatment and progressed quickly, which didn't achieve the desired effect. G719S mutant is supposed to be the cause of poor responsive to treatment.

Background: Metastasis of squamous cell carcinoma (SCC) to the superior cervical ganglion (SCG) has never been reported. Its anatomic location may easily be mistaken for a retropharyngeal lymph node. We present the first case of SCC metastasis to the SCG., Methods: We report a case of a 69year-old never smoking male, who presented with right retropharyngeal PETCT-avid disease following chemoradiation for squamous cell carcinoma of the tonsil. He was brought to the operating room for resection, intraoperative radiation and reconstruction., Results: Intraoperatively, visualization and frozen section confirmed squamous cell carcinoma located in the superior cervical ganglion. The ganglion was resected, intraoperative radiation was given and the patient was reconstructed with a radial forearm free flap. Postoperatively, the patient displayed features of a Horner's syndrome., Conclusions: The superior cervical ganglion may be mistaken for a retropharyngeal lymph node. Although extremely rare, these entities may be differentiated on the basis of radiological studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV)-positive tonsillar- and base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negative cancer and most other head and neck cancers with around 80% 3-year disease free survival with conventional radiotherapy and surgery. Consequently, most HPV-positive cancer patients may not require the intensified chemoradiotherapy given to many head and neck cancer patients and would, with tapered treatment, avoid several severe side-effects. Moreover, intensified therapy has not improved survival and treatment alternatives are needed. To identify patients eligible for tapered or targeted therapy, additional biomarkers are required. Several studies have, therefore, focused on finding predictive markers, some of which are also potentially targetable. To conclude, better-tailored therapy, either as tapered or targeted, is important for increasing numbers of patients with HPV-positive tonsillar- and base of tongue cancer. This review deals with some of these issues and presents some promising markers., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Porphyria is a condition of cutaneous photosensitivity. It is unclear if radiotherapy (RT) is safe in patients with porphyria., Methods: We report a patient case with uncontrolled porphyria cutanea tarda treated with chemoradiation for p16-positive oropharyngeal cancer. Given the scarcity of data on this subject, we also conducted a literature review on the topic of radiation in patients with porphyria., Results: The patient in our study did not experience any unusual acute or late toxicity, despite receiving a high dose of cutaneous radiation. We also found the majority of the literature supports the safe use of therapeutic radiation in patients with porphyria., Conclusion: In this patient, and in the majority of the literature, radiation seems safe in patients with porphyria; however, there are few reports on the subject in the literature, therefore, caution is warranted., (© 2017 Wiley Periodicals, Inc.)

Background: Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches., Methods: We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed., Results: At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively)., Conclusions: In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes.

Objective Compare survival outcomes between unimodality and multimodality treatments for early-stage tonsil squamous cell carcinoma (SCC). Study Design and Setting Review of the National Cancer Database. Subjects and Methods Patients were selected if they were <70 years old with clinical stage I-II SCC of the tonsil, as documented in the National Cancer Database from 1998 to 2011. Palliative and nonstandard treatments were excluded. Propensity score matching was performed, controlling for tumor stage, age, race, comorbidity, insurance status, and year of diagnosis. Overall survival (OS) was compared with the Kaplan-Meier method and log-rank test. Results We identified 3247 patients. Radiotherapy (RT) was delivered in 1295 patients (39.9%), surgery in 824 (25.4%), and surgery + RT in 1128 (34.7%). Patients treated with surgery + RT had the highest 5-year OS (81.1%), followed by surgery (67.4%) and RT (63.4%; P < .001). In a propensity score-matched subpopulation of 2378 patients, the 5-year OS was 78.8% for surgery + RT, 66.7% for surgery, and 64.5% for RT ( P < .001). Among patients who underwent surgical tonsillectomy plus elective neck dissection and/or adjuvant RT, the 5-year OS was equal ( P = .29), and all were superior to RT alone ( P < .001). Conclusion Multimodality treatment is associated with the greatest survival in early-stage tonsil cancer. The addition of tonsillectomy to RT confers a 20% increase in survival. The current guidelines might not offer the most effective treatment. An up-front surgical approach, followed by appropriately selected adjuvant therapy, may result in improved survival for early-stage tonsil SCC. These findings merit investigation in a prospective clinical trial.

We report a case of follicular dendritic cell sarcoma (FDCS) in a 60-year-old Ugandan female who presented with a 6-year history of a progressive left sided tonsillary mass. General systemic examination was unrevealing and the patient underwent left tonsillectomy. She was subsequently lost to follow-up. Grossly, the mass measured 6 cm in diameter and had a mottled appearance due to tissue microhaemorrhages. Markers specific for follicular dendritic cell differentiation (CD21, CD35 and CD23), p53 and EGFR were expressed on immunohistochemical analysis. Review of all of the 49 published reports of tonsil FDCS showed that this entity tended to occur at younger age (mean: 44.5 yrs) in women than in men (mean: 49.4 yrs). Tumour size ranged from 0.8 to 5 cm in maximum dimension (mean 2.9 cm). Only 12.2% of the patients presented with metastatic disease at initial diagnosis, all localised in the cervical lymph nodes. Local or distant recurrences occurred after a mean period of 72.5 months. In conclusion, although the pertinent literature suggests that FDCS should be considered at least of intermediate grade, our review indicates that FDCS of the tonsil region behaves as a low-grade sarcoma., (© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Objectives/hypothesis: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors., Study Design: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011., Methods: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival., Results: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa., Conclusions: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy., Level of Evidence: 4 Laryngoscope, 127:1087-1092, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Paraneoplastic neurological disorders are uncommon presentations of head and neck cancers. We present a case of a 68-year-old male patient who presented with dizziness, nausea and memory problems. MRI of his brain showed bilateral cerebellar leptomeningeal enhancing signal abnormality with cervical lymphadenopathy. CT imaging of his neck raised the suspicion of a tonsillar primary, which was later confirmed on biopsy. His poorly differentiated HPV positive squamous cell carcinoma was treated with chemoradiotherapy. Subsequent MRI imaging showed progressive cerebellar atrophy and his presenting symptoms persisted, but he remained disease free 6 months post-treatment for his primary malignancy., Competing Interests: Conflicts of Interest: None declared., (2017 BMJ Publishing Group Ltd.)

Many tonsillar tumors present clinically as cervical nodal metastases and the primary tumor is often difficult to find. HPV-driven tonsillar carcinoma begins in the reticulated crypt epithelium, possibly through viral integration. The basement membrane is not complete in the reticulated crypt epithelium, which may enhance the immune function. We examined the reticulated crypt epithelium in a normal case and five neoplastic tonsils with cervical metastasis as the presenting symptom to further investigate whether tonsil carcinoma in-situ exists. Our results suggest that in-situ carcinoma may need to be excluded from the future staging for human papilloma virus associated tonsillar tumors.

A 7-year-old boy was referred for evaluation of loud nightly snoring. Snoring started suddenly 2 weeks prior to presentation and grew progressively worse. Currently, the parents witnessed breathing pauses and gasping at night. The parents moved the child to a recliner to be able to breathe better, but the snoring and apneas persisted. There was no sleepwalking, night terrors, or nocturnal enuresis. During the day, the boy did not endorse symptoms of excessive sleepiness. The review of systems was negative for fever, weight loss, night sweats, sore throat, dysphagia, nasal congestion, ear pain, chest pain, shortness of breath, stridor, and abdominal pain. The child did not complain of throat discomfort. The parents noticed a sudden change in the child's voice and described it as "muffled, like speaking with cotton balls in his mouth." His school performance did not change. He had had a viral illness 2 weeks prior to presentation that was diagnosed as viral pneumonia. He was not on medications., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Chemoradiotherapy (CRT) has become the mainstay of treatment for tonsillar squamous cell carcinoma (SCC). Pre-CRT tonsillectomy is frequently performed, mostly for small primary tumors (T1-T2). However, the benefits of pre-CRT tonsillectomy remain unclear., Methods: A retrospective review was performed in 66 patients with T1-T2 tonsillar SCCs treated by CRT from 1997 to 2009. The efficacy of pre-CRT tonsillectomy was analyzed with regard to oncological and functional outcomes., Results: Thirty patients (45.5%) received tonsillectomy (pre-CRT tonsillectomy group), and 36 patients (54.5%) did not (CRT group). Except for a trend toward more T1 cases (33.3% vs. 13.9%, p = 0.061) and significantly less chemotherapy use (60% vs. 86.1%, p = 0.016) in the pre-CRT tonsillectomy group, there were no differences between the two groups in terms of age, gender, N classification (nodal status), overall stage, radiation dose, duration, or technique. In the pre-CRT tonsillectomy group, eight cases (26.7%) achieved an adequate operative margin judged by the surgeon, and only one (12.5%) had a negative pathological margin. In long-term follow-up, there were no statistically significant differences between the two groups regarding local (93.3% vs. 91.7%, p = 0.82) or regional control (93.3% vs. 94.4%, p = 0.84). The pre-CRT tonsillectomy group did not have a better 5-year disease-specific survival rate (83.3% vs. 94.4%, p = 0.177) or 5-year overall survival rate (70% vs. 94.4%, p = 0.017). There were no differences in complications or functional results (feeding tube and tracheostomy dependence), and quality of life demonstrated no significant difference., Conclusion: Pre-CRT tonsillectomy contributes little to oncological and functional outcomes in patients with T1-T2 tonsillar SCC., (Copyright © 2016. Published by Elsevier Taiwan LLC.)

Background: Human papillomavirus (HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC., Methods: We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type., Results: HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR=19.8; P=0.040) and low CD8/CD4 ratio (HR=7.7, P=0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR=15.2; P=0.03) and low CD8 (+)/CD4 (+) ratio (HR=3.3; P=0.04)., Conclusions: The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Three-year survival is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and higher (95-100%) in patients with tumors without HLA class I expression, or with high CD8(+) tumor-infiltrating lymphocyte (TIL) counts. The former paradoxical, the latter expected, but it is known that E5 and E7 can downregulate HLA class I expression. Furthermore, upon HPV integration, E2, sometimes in combination with E5 is lost. Here, HPV16 E2, E5 and E7 mRNA was therefore examined in relation to HLA class I expression, TIL counts and survival., Patients and Methods: HPV16 DNA positive TSCC and BOTSCC biopsies, analyzed for HLA class I and CD8(+) TILs, of 133 patients, treated curatively between 2000 and 2011, were tested for HPV16 E2, E5 and E7 mRNA expression. Totally 127 samples could be evaluated and of these 117 patients, all with HPV16/E7-mRNA-positive tumors, were included in the final analysis., Results: Most tumors (92%) expressed E7 mRNA, and of these 64% also expressed E2 and E5 mRNA. Patients with tumors lacking E2 mRNA had worse 3-year relapse and progression free survival (p<0.01 and p<0.05), while presence of E5 had no impact on clinical outcome. Furthermore, HLA class I expression and TILs were not correlated to E5 or to E2 mRNA expression., Conclusion: Lack of E2 but not E5 mRNA in HPV16 positive TSCC and BOTSCC was a negative prognostic marker. Presence of HPV16 E2, E5 and E7 mRNA expression was not correlated to HLA class I expression or CD8(+) TILs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The nasopharyngeal/oropharyngeal lymphatic tissues represent the anatomical site of Epstein-Barr virus (EBV) entry. Post-transplant lymphoproliferative disorders (PTLD) are often associated with EBV, but little is known about the characteristics of nasopharyngeal/oropharyngeal mass-forming PTLD. Retrospective evaluation of our own PTLD database (n = 79) and the PubMed(®) database (n = 61) has been performed. Sinonasal/oro-/nasopharyngeal lymphatic masses were early lesions (n = 54/140, 38.5%), polymorphic PTLD (n = 32/140, 23%), monomorphic B-PTLD (n = 47/140, 33.5%) and T-PTLD (n = 7/140, 5%). One-fourth of lesions manifested as masses in the Waldeyer's ring, and in two-thirds of cases, swelling of tonsils was related to manifestation of benign early lesions. Tonsil infiltration by polymorphic PTLD and monomorphic PTLD was present in one-third of cases. Extratonsillar masses were mainly monomorphic PTLD. Meta-analysis of our data in combination with previously published data revealed that lung transplantation and young patients are at a higher risk for earlier manifestation of monomorphic PTLD. Therapy is similar to PTLD therapy strategies, in general reduced immunosuppression and chemotherapy for polymorphic and monomorphic PTLD, and diagnostic and therapeutic surgical gross tumour resection of tonsillar/adenoid lesions. In summary, it is relevant for the clinical differential diagnosis that oro-/nasopharyngeal aggressive PTLD manifested in ~30% as tonsillar masses and >90% at extratonsillar sites., (© 2015 Steunstichting ESOT.)

Objective: The cost of treatment as it affects comparative effectiveness is becoming increasingly more important. Because cost data are not readily available, we evaluated the charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancers., Methods: Patients treated with unilateral radiation therapy (RT) for T1 or T2 tonsil cancer between 1995 and 2007 were retrospectively reviewed. Total and radiation-specific charges, from 3 months before to 4 months after radiation, were adjusted for inflation. All facets of treatment were evaluated for significant associations with total billing., Results: Eighty-four patients were identified. Three-year overall survival, disease-specific survival, and recurrence-free survival were 97 % [95 % confidence interval (CI) 0.88-0.99], 98 % (95 % CI 0.89-1), and 96 % (95 % CI 0.88-0.99), respectively. The median for radiation-specific charges was $60,412 (range $16,811-$84,792). The median for total charges associated with treatment was $109,917 (range $36,680-$231,895). Total billing for treatment was significantly associated with the year of diagnosis (p = 0.008), intensity-modulated radiation therapy versus wedge pair RT (p = 0.005), preradiation direct laryngoscopy (p < 0.0001), chemotherapy (p < 0.0001), gastrostomy tube placement (p = 0.004), and postradiation neck dissection (p = 0.005)., Conclusions: Although cost data for treatment are not readily available, historically, the recovery rate is approximately 30 %. The charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancer have a wide range likely due to treatment-related procedures, the use of chemotherapy, and evolving RT technologies. These benchmark data are important given renewed interested in primary surgery for tonsil cancer. Cost of care, disease control, and functional outcomes will be critical for comparisons of effectiveness when selecting treatment modalities.

Objective: We describe an unusual foreign body, a carotid stent extruded into the upper airway, and discuss the predisposing factors., Methods: This is a single patient case report with review of the literature., Results: Our patient is a 59 year old female treated for T3N2aM0 (stage IVa) left tonsil squamous cell carcinoma who experienced a carotid blowout treated by carotid stent placement with subsequent carotid coiling and vessel takedown. Approximately ten months later, she coughed and expelled approximately 3cm of tubular stent-appearing material into her airway causing acute stridor and dysphagia. CT angiography (CTA) showed the distal and proximal stent in proper position without evidence of extravasation. The stent was extracted transorally showing the distal end of the carotid to be patent and covered by fibrin within its lumen. Review of the literature shows that such stent extrusions, although rare, do occur., Conclusion: Carotid stents are a valuable tool in cases of carotid blowout. However, long-term data on patient prognosis is lacking. The foreign body response triggered by stent placement can cause dislodgement. The potential for stent extrusion is greatest in patients who have preexisting ulceration or who have undergone radiation, both common in head and neck cancer patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In 2007, human papillomavirus (HPV) type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC), where tonsillar and base of tongue cancer (TSCC and BOTSCC) dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20-40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects) often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.

An adenovirus harboring the HSV thymidine kinase (HSVtk) gene under the regulation of a trans-splicing ribozyme that targets telomerase is cytotoxic to cancer cells because it inhibits DNA replication (Ad5mTR). Furthermore, it induces anti-tumor immunity by activating cytotoxic T cells. Because multiple chemotherapeutic agents also activate cytotoxic T-cell immunity during the direct killing process of tumor cells, we herein explored whether low-dose cisplatin could synergize with cytotoxic Ad5mTR to potentiate its therapeutic effect by boosting anti-tumor immunity in a murine HPV16-associated tonsillar carcinoma model. Tumor regression was enhanced when low-dose (1 mg/kg) cisplatin was added to suicide gene therapy using Ad5mTR. Meanwhile, 1 mg/kg cisplatin alone had no tumor-suppressive effects and did not result in any systemic toxicity. Thus, cisplatin along with Ad5mTR improved tumor clearance by increasing the number of E7-specific CD8+ T cells. Specifically, analysis of the tumors and lymph nodes supported improved immune clearance by increasing the number of E7-specific CD8+ T cells inside tumors (40%, P < 0.05) as a result of the combination of suicide gene and cisplatin therapy. These results suggest that a low dose of cisplatin potentiates CD8+ T-cell-mediated anti-tumor immunity, and its addition to the HSVtk-based adenovirus results in additional therapeutic benefits for HPV16-positive head and neck cancer patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Osteoradionecrosis of the hyoid bone is a rare complication of therapeutic irradiation performed for head and neck cancer. In this article, we present a 52-year-old male patient who admitted with severe odynophagia following chemo-radiotherapy administration for tonsil carcinoma. Fluorine-18-fluorodeoxy-glucose positron emission tomography-computed tomography revealed a metabolic activity in hyoid bone. The pathological findings were consistent with fungal infection and hyoid bone necrosis. Hyoid osteoradionecrosis should be kept in mind in patients with intractable dysphagia following irradiation for head and neck tumors.