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Sexuality and sexual intimacy are important aspects of cancer survivorship. In head and neck cancer (HNC), concerns around sexual health, sexuality and sexual intimacy are infrequently raised or addressed in standard HNC consultations, either before embarking on treatment or during survivorship. The changing demographic of HNC patients, largely due to the increasing proportion of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC), has driven renewed interest in some specific survivorship issues, including sexual behaviours and lifestyles, which may account for both the primary mode of HPV transmission and the younger and less comorbid population affected by this disease. While HNC survivors may have many complex needs in the short and longer term, some patients may prioritise preserving sexual function above other more HNC-specific issues, such as swallowing and xerostomia. Beyond HPVOPSCC, there is evidence to suggest that impairment of sexual health is a pervasive survivorship issue across all HNC cancer types, and this narrative review article highlights publications reporting quantitative assessments of sexual health outcomes in HNC patients. There are also limited studies evaluating whether current sexual health models of care are adequate for HNC patients or whether new or adapted models are needed. Future research will also need to define the impact of our treatments on the sexuality and sexual intimacy concerns of specific HNC cohorts with more granularity to enhance pre- and post-treatment counselling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To develop consensus on patient characteristics and disease-related factors considered in deciding treatment approaches for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) based on real-world treatment patterns in 4 territories in Asia-Pacific., Methods: A three-round modified Delphi involving a multidisciplinary panel of HN surgeons, medical oncologists, and radiation oncologists was used. Of 41 panelists recruited, responses of 26 from Australia, Japan, Singapore, and Taiwan were analyzed. All panelists had ≥five years' experience managing LA-HNSCC patients and treated ≥15 patients with LA-HNSCC annually., Results: All statements on definitions of LA-HNSCC, treatment intolerance and cisplatin dosing reached consensus. 4 of 7 statements on unresectability, 2 of 4 on adjuvant chemoradiotherapy, 7 of 13 on induction chemotherapy, 1 of 8 on absolute contraindications and 7 of 11 on relative contraindications to high-dose cisplatin did not reach consensus. In all territories except Taiwan, high-dose cisplatin was preferred in definitive and adjuvant settings for patients with no contraindications to cisplatin; weekly cisplatin (40 mg/m 2 ) preferred for patients with relative contraindications to high-dose cisplatin. For Taiwan, the main treatment option was weekly cisplatin. For patients with absolute contraindications to cisplatin, carboplatin ± 5-fluorouracil or radiotherapy alone were preferred alternatives in both definitive and adjuvant settings., Conclusion: This multidisciplinary consensus provides insights into management of LA-HNSCC in Asia-Pacific based on patient- and disease-related factors that guide selection of treatment modality and systemic treatment. Despite strong consensus on use of cisplatin-based regimens, areas of non-consensus showed that variability in practice exists where there is limited evidence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: As part of a program to reduce numbers of the human pathogen Campylobacter on retail chickens, 22 broiler processing lines, representing more than 90% of UK production, were characterized by enumerating Campylobacter on pooled neck skins after exsanguination, scalding, defeathering, evisceration, crop removal, inside-outside washing, and air-chilling stages of processing. Sixteen of the processing lines investigated showed significant (P < 0.05) reductions in Campylobacter numbers because of carcass scalding. However, in all of these lines, the following defeathering stage caused a significant increase in Campylobacter contamination that effectively negated the reductions caused by scalding. On four processing lines, primary chilling also caused a significant reduction in numbers of Campylobacter. On three lines, there was a significant microbiological benefit from inside-outside washing. The stages where Campylobacter numbers were reduced require further investigation to determine the specific mechanisms responsible so that the observed pathogen reductions can be optimized and then more widely implemented. The transfer of up to 4 log CFU Campylobacter per g of neck skin from a colonized flock to a following uncolonized flock was observed. Cross-contamination was substantial and still detectable after 5,000 carcasses from an uncolonized flock had been processed. Numbers of Campylobacter recovered from the uncolonized flocks were highest on the first of the uncolonized birds to pass along the line, and in general, the numbers declined as more uncolonized birds were processed. Air sampling recovered low numbers at the processing stages monitored, indicating that airborne transmission was unlikely to be the primary transfer mechanism operating for cross-contamination between flocks., (Copyright ©, International Association for Food Protection.)

Objectives: Evidence to support Epstein-Barr virus (EBV)-directed population nasopharyngeal carcinoma (NPC) screening has been growing. Familial aggregation is a well-recognized phenomenon in endemic regions. This systematic review summarizes the role of EBV-directed screening in individuals with a positive family history (FH+) of NPC., Methods: We searched four electronic databases from their inception to October 2021. We included studies on individuals with FH+ of NPC who had undergone EBV-directed investigations, with no restriction in the testing methods or analytic techniques. The primary and secondary outcomes were EBV positivity rates and NPC incidence rates, respectively. Meta-analyses were performed using the random-effect model., Results: Ten cross-sectional studies (n = 7436) and three cohort studies (n = 4306) were included. The pooled relative risk (RR) of EBV positivity between individuals with and without FH+ of NPC were 2.79 (95 % CI 1.37-5.68, p = 0.005) for viral capsid antigen (VCA) IgA, 3.09 (95 % CI 0.65-14.83, p = 0.16) for Epstein-Barr nuclear antigen (EBNA1) IgA, and 1.76 (95 % CI 1.04-2.96, p = 0.03) for combined EBNA1/VCA IgA. In the three cohort studies, the NPC incidence rates ranged from 90.2 to 266 per 100 000 person-years with high proportions of early-stage diseases. FH+ individuals who were EBV-positive had a 2.5 to 30.7-fold risk of NPC development compared to their EBV-negative counterparts., Conclusion: Family members of NPC patients had significantly higher EBV positivity rates than the general population. FH+ individuals who are EBV-positive had high risks of developing NPC. Familial screening using EBV serology may facilitate early NPC detection in endemic areas., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: High CD103 + intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis., Patients and Methods: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103 + ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial., Results: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103 + ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS., Conclusions: CD103 + ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials., Competing Interests: Disclosure DR—grants from Merck Sharp & Dohme, grants from Merck KGaA, grants from Bristol-Myers Squibb, grants from GSK, grants from Roche, grants from Regeneron, grants from Kura Oncology, grants from ALX Oncology, trial steering committees and/or advisory boards (all uncompensated)—MSD, GSK, Regeneron, Sanofi; HM—grants from Astra Zeneca, grants from GSK Biologicals, grants from GSK, trial steering committees and/or advisory boards—Astra Zeneca, Merck Sharp and Dohme, Merck KGaA and GSK; JC—grants from Merck KGgA, advisory board Merck KGgA Sandro Porceddu—advisory boards Merck Sharp & Dohme, Merck KGgA, Steering Committee Regeneron; CW—advisory board Merck KGgA; BJS—research grant from Sanofi-Regeneron; advisory boards or consultancies—Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, Roche/Genentech, Amgen, Lilly, Sanofi, Glaxo-Smith Kline, Takeda and BeiGene; has been compensated for royalties UpToDate. All other authors have declared no conflicts of interest., (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The emergence of human papillomavirus-associated oropharyngeal cancer (HPVOPC) has resulted in an explosion of clinical research offering reduced toxicity and improved health-related quality of life (HRQL) through treatment de-escalation. At the heart of this objective are patient-reported outcomes (PROs) which aim to quantify the patient experience, usually through the measurement of HRQL or symptom burden. A number of PRO measures (PROMs) are available to HNC researchers and selection of the optimal instrument relies on a detailed understanding of their content and psychometric properties matched to the clinical endpoint of interest. As PROMs become increasingly favoured as the primary or co-primary endpoints of interest in HNC clinical trials, particularly those focussed on HPVOPC, future treatment paradigms will be determined by these measures and it is imperative that they are applied with sophistication and rigor. This review draws attention to the limitations and challenges our specialty faces in PRO application, analysis and reporting. These shortfalls typically include a reliance on statistical rather than clinically relevant differences, multiple hypothesis testing, a lack of evidence-based minimal clinically important differences for the commonly used tools, as well as variations in PROM selection. The aim of this review is to provide: (1) an overview of PRO/PROM terminology and methodology in the HNC setting; (2) to provide a summary of HRQL and symptom burden reports in the HPVOPC literature; and (3) to draw attention to the unmet research need of refining PROM development, application and interpretation to guide our treatment decisions based on what matters to patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Accurate determination of human papilloma virus (HPV) status is critical when identifying patients with oropharyngeal squamous cell carcinoma (OPSCC) who may be candidates for de-escalation trials. In this study we investigated whether local p16 screening, by immunohistochemistry (IHC), has high positive predictive value (PPV) for HPV status in a good prognosis HPV positive OPSCC (HPVOPSCC) population treated on a clinical trial., Methods and Materials: Patients enrolled on the TROG 12.01 randomised trial for good prognosis HPVOPSCC were randomised based on local p16 IHC testing but subsequently had central p16 IHC and HPV RNA in situ hybridisation (HPV RNA ISH) testing. Correlations between the local and central p16 and central HPV RNA ISH were studied. The main outcome was the positive predictive value (PPV) of local pathology laboratory testing of p16., Results: 176/182 patients had samples available for central testing. 172/176 were evaluable for central testing of p16, and all were confirmed to be p16 positive (172/172, 100%, 95% CI = [97.9%, 100%]). Similarly, 100% of those evaluable for HPV RNA ISH (155/155, 100%, 95% CI = [97.6%, 100%]) were confirmed HPV positive, indicating p16 overexpression driven by transcriptionally active HPV and a PPV of 100% for local p16 testing., Conclusions: Our results validate the suitability of local pathology laboratory p16 testing alone, in populations with a high attributable fraction of OPSCC due to HPV, to screen and enrol low risk HPVOPSCC patients onto de-intensification trials. This obviates the need for upfront more complex and expensive HPV assays and/or central laboratory testing., Competing Interests: Declaration of Competing Interests Richard Young - institutional grant from Roche; Ben Solomon - personal fees from Merck Sharp & Dohme, personal fees from Bristol-Myers Squibb, grants and personal fees from Roche, grants from Regeneron, personal fees from AstraZeneca, grants and personal fees from Pfizer, personal fees from Genentech, personal fees from Loxo Oncology; Christopher Angel - institutional grant from Roche; Sandro Porceddu - personal fees from Merck Sharp & Dohme, personal fees from Merck, personal fees from Celgene; Danny Rischin - grants from Merck Sharp & Dohme, grants from Merck, grants from Bristol-Myers Squibb, grants from GSK, grants from Roche, grants from Regeneron, grants from Amgen, grants and personal fees from MSD, Trial Steering Committees and/or Advisory Boards (all uncompensated) - MSD, Merck, Bristol-Myers Squibb, GSK, Regeneron; June Corry, Christopher Wratten, Andrew Macann, James Jackson, and Alan Herschtal - no disclosures., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JA Langendijk: Departmental research collaboration with RaySearch, IBA, Siemens, Mirada and Elekta. Member of the International Advisory Board of IBA, honorarium paid to UMCG Research BV. Nabil F. Saba: Consulting for Merck, Aduro, Rakuten, Pfizer, CUE, Blupoint, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Treatment package time (TPT) prolongation is associated with lower overall survival and locoregional control in mucosal head and neck squamous cell carcinoma (SCC), but there are few reports in cutaneous HNSCC (cHNSCC). We sought to test the effect of TPT in a cohort of patients with cHNSCC., Methods: This is a single institution retrospective study of node-positive cHNSCC patients involving either the parotid or cervical nodes treated with curative intent surgery with macroscopic tumor clearance followed by standard fractionation postoperative radiation therapy (PORT) from 2001 to 2014. We assessed the effect of TPT and other prognostic variables on overall survival (OS), cHNSCC specific survival (CSS) progression free survival (PFS), and freedom from locoregional failure (FFLRF)., Results: In the present study, 152 patients met the inclusion criteria. The 5-year OS, CSS, PFS, and FFLRF were 62% (95% confidence interval [CI], 54-71), 78% (95% CI, 71-87), 54% (95% CI, 46-64), and 76% (95% CI ,68-85), respectively. In a multivariable model, TPT ≥14 weeks was associated with worse outcomes in all endpoints (OS [hazard ratio (HR) 4.93; 95% CI, 2.54-9.56, P < .001], CSS [HR 6.09; 95% CI, 2.33-15.92; P = .001], PFS [HR 4.29; 95% CI, 2.21-8.34; P < .001], and FFLRF [HR 4.63; 95% CI, 1.71-12.51; P = .007]). Immunosuppression and the presence of ≥2 pathologically involved lymph nodes were also significant adverse factors for both OS and FFLRF, although extracapsular extension was also associated with lower FFRLF. Delays to commencing PORT rather than treatment breaks accounted for the majority of cases with prolonged TPT., Conclusions: Prolongation of TPT to 14 weeks or longer may confer a lower probability of locoregional control and survival in patients with lymph node-positive cHNSCC treated with surgery and PORT. Timely referral and commencement of PORT is necessary to maximize long-term disease outcomes., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Highlights: Campylobacter levels on chicken neck and breast skin were compared. Neck skin was significantly more contaminated ( P < 0.05) than breast skin. No relationship between the two skin types was found for Campylobacter levels. A UK government reduction target for highly contaminated chicken was not achieved.

Head and Neck Cancer (HNC) radiation oncologists (ROs) enjoy the immense pleasure of curing patients, working within a large multidisciplinary team to effectively deliver curative intent treatment whilst also aiming to minimise late treatment toxicity. Secondary analyses of large-scale HNC clinical trials have shown the critical impact of the quality of radiotherapy plans, where protocol non-compliant plans have yielded inferior survival rates approximating 20%. The peer review process in routine day-to-day HNC practice shows that even in major academic centers a significant proportion of RT plans may require changes to the radiotherapy planning volume. Optimising the therapeutic ratio in HNC has been dramatically facilitated by intensity modulated radiotherapy (IMRT), but that technology has also increased the complexity of HNC radiotherapy treatment and high-volume centers with experienced clinicians may be best placed to deliver this most accurately. International consensus guidelines to standardise or benchmark best practice with respect to the RT-QA process in HNC are needed. The aim of this paper is to highlight the importance of the RT-QA process in the HNC treatment process and to make some recommendations for its inclusion in both clinical trials and routine clinical practice., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe life-threatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer patients, with a focus on the critical assessment of the treatment options for xerostomia, dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Prognostic information can rationalise clinical follow-up after radical cancer treatment. This retrospective cohort study of radical head and neck (chemo)radiotherapy patients examines the clinical safety and cost implications of stratifying follow-up intensity by post-treatment (18)FDG-PET-CT response., Methods: In 2008 clinical review after radical head and neck radiotherapy was reduced from 3- to 6-monthly for patients with complete (18)FDG-PET-CT response at 3months. 184 patients treated after this change ("PET Stratified", 2009-11) were compared to 178 patients treated before ("Standard", 2005-7). Clinical safety was assessed by the time to detection of recurrence, overall survival and potential for radical treatment of recurrence. A hospital cost analysis was performed using individual patient data., Results: 127 of 178 Standard and 148 of 184 PET Stratified patients achieved complete response on post-treatment imaging. Baseline clinical characteristics were comparable. Median follow-up from response assessment was 4.8years in the Standard cohort and 2.1years for PET Stratified. PET Stratified patients had a mean 4.4 outpatient visits in 2years, compared to 7.0 among Standard patients. Over 90% of patients remained free of recurrence at 2years in both cohorts. Time to detection of recurrence was similar between two cohorts (HR1.05, 95%CI 0.45-2.52), as was overall survival (HR0.91, 95%CI 0.36-2.29). The proportion of radically treatable recurrences was also similar (42% Standard vs. 47% PET Stratified). The hospital cost savings per patient from reduced review were AUD$2606 over 2years, AUD$5012 over five., Conclusion: (18)FDG-PET-CT to stratify follow-up intensity after radical radiotherapy for head and neck cancer reduces costs with no apparent clinical detriment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To investigate disease control and functional outcomes in patients with T4 squamous cell carcinoma of the oral tongue who had undergone surgery or definitive chemoradiotherapy., Study Design: Records of all consecutive patients with T4 squamous cell carcinoma of the oral tongue treated radically between 1999 and 2010 at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, were retrospectively reviewed., Results: Of 31 patients, 19 underwent surgery and 12 underwent definitive chemoradiotherapy. There were no significant differences between cohorts in terms of age, nodal involvement, or performance status. All patients had T4 disease on the basis of extrinsic muscle invasion; none had bone invasion. Disease outcomes at 5 years after surgery or chemoradiotherapy were not significantly different, including local control (61% vs 70%), progression-free rate (56% vs 55%), and overall survival (27% vs 40%). A higher proportion of patients in the chemoradiotherapy group had only mild impairment of speech and swallowing., Conclusions: Definitive chemoradiotherapy may be a reasonable alternative to surgery for patients with T4 squamous cell carcinoma of the oral tongue without bony invasion., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Purpose: This study used prospective swallowing data to establish the following: (1) whether doses to the pharyngeal constrictor muscles (PCMs) were significantly associated with swallowing outcomes; and (2) a mean dose constraint to aim for in intensity modulated radiation therapy planning., Methods and Materials: The PCMs were contoured and radiation dose data obtained for 55 patients with head and neck cancer. Associations between radiation dose and percentage of pharyngeal residue, penetration-aspiration and activity limitation measured at 6 months posttreatment were analyzed. Pretreatment swallowing function, tumor site, T classification, and chemotherapy were accounted for in multivariate analyses., Results: On multivariate analysis, the percentage of pharyngeal residue was statistically significantly associated with the mean dose to the superior PCM (95% confidence interval [CI], 0.15-1.66; P = .02). Penetration-aspiration was associated with the mean dose to the superior, middle, and inferior PCMs (95% CI, 1.02-1.27; P = .003; 95% CI, 1.02-1.23; P = .003; 95% CI, 1.04-1.21; P = .003, respectively) and the mean dose to the total PCM (95% CI, 1.05-1.31; P = .001). Activity limitation was also associated with the mean dose to the superior, middle, and inferior PCMs (95% CI, 1.01-1.20; P = .02; 95% CI, 1.00-1.15; P =.04; 95% CI, 1.01-1.15; P = .02, respectively) and the mean dose to the total PCM (95% CI, 1.02-1.23; P = .01). On univariate analysis, all 3 swallowing measures were statistically significantly worse for patients who received a biologically equivalent mean dose of >60 Gy to the PCMs. This remained significant on multivariate analysis for both penetration-aspiration and activity limitation (95% CI, 2.05-58.2, P = .004 and 95% CI, 1.14-27.7, P = .03, respectively)., Conclusions: The radiation dose to the PCMs is significantly associated with swallowing dysfunction. Limiting the mean PCM dose to less than 60 Gy results in better swallowing outcomes., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Objectives: Novel therapies are required for patients with recurrent or metastatic oral tongue squamous cell carcinoma (OTSCC). Fibroblast Growth Factor Receptor 1 (FGFR1) amplification frequently occurs in squamous cell carcinoma of the lung and represents a novel druggable therapeutic target in this and other malignancies. This study examined the frequency and clinical associations of FGFR1 amplification in OTSCC., Materials and Methods: The frequency of FGFR1 amplification determined by fluorescence in situ hybridization was evaluated in a cohort of 123 OTSCC patients. Associations of FGFR1 amplification with clinical characteristics and outcome were determined., Results: FGFR1 gene amplification was present in 9.3% (10/107) of cases and was significantly associated with smoking status (P = 0.03). FGFR1 amplification was seen more commonly in males (9/10 amplified cases male, P = 0.16) and there were no associations with age, stage, T stage, nodal status, alcohol history or performance status (all P>0.05). Outcome was not significantly different between FGFR1 amplified and non-amplified patients., Conclusions: Copy number variations of the FGFR1 gene occur in a subset of OTSCC with approximately 10% of cases showing amplification of the gene. FGFR1 amplification may represent a therapeutic target in OTSCC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the tolerability and feasibility of induction gemcitabine and carboplatin chemotherapy followed by radiotherapy with concurrent cisplatin in patients with locally advanced nasopharyngeal carcinoma., Patients and Methods: Twenty-eight patients with previously untreated non-keratinising nasopharyngeal carcinoma, with stage IIb to IV disease were enroled to receive three cycles of carboplatin AUC 5 and gemcitabine 1 g/m(2) day 1 and 8 every 21-days, followed by 70 Gy of radiotherapy with concurrent cisplatin 20 mg/m(2)/day for 5 days of weeks 1, 4 and 7., Results: 26/28 (93.0%) patients received all three cycles of induction chemotherapy. All 27 patients who commenced chemoradiotherapy received 70 Gy in 35 fractions of radiotherapy with at least two cycles of concurrent cisplatin. The three-year time to locoregional failure rate was 92.9% (95% CI: 75.5-98.2%) and the three-year overall survival rate was 89.3% (95% CI: 71.6-96.5%). Induction chemotherapy was well tolerated with 5/28 (17.9%) patients experiencing grade 3 non-haematological toxicities and no reported episodes of febrile neutropenia or grade 4 toxicity. For the 27 patients who received radiotherapy, no acute grade 4 radiation toxicities and only 2/27 (7.4%) late grade 4 radiation adverse events were observed., Conclusion: The use of induction carboplatin and gemcitabine followed by chemoradiotherapy is feasible, with acceptable toxicity, and is a promising regimen for the treatment of locally advanced nasopharyngeal carcinoma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer., Patients and Methods: A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression., Results: The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes., Conclusions: This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination of the surgical specimen (microscopic), or may present with cranial nerve (CN) deficits (clinical). The V and VII CNs are most commonly involved. Magnetic resonance imaging (MRI) may be obtained to detect and define the extent of PNI; computed tomography (CT) or ultrasound-guided fine needle aspiration cytology (UGFNAC) may assist with detecting or excluding regional lymph node metastases. Patients with apparently resectable cancers undergo surgery, usually followed by postoperative radiotherapy (RT). Patients with unresectable cancers are treated with definitive RT. Moreover, RT may be considered if significant functional or cosmetic impairment is expected after surgical treatment. The 5-year outcomes after treatment for clinically unsuspected microscopic compared with clinical PNI are: local control, 80% and 55%; cause-specific survival, 75% and 65%; and overall survival, 55% and 50%, respectively. The incidence of grade ≥ 3 complications is higher after treatment for clinical PNI versus microscopic PNI; approximately 35% compared with 15%, respectively. Proton beam RT may be used to reduce the risk of late complications by reducing RT dose to the visual apparatus and central nervous system (CNS)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Ataxia-Telangiectasia-Mutated (ATM) gene loss has been associated with poor prognosis and treatment resistance in head and neck squamous cell carcinomas (HNSCC). We investigated the relationship between ATM loss detected by fluorescence in-situ hybridisation (FISH) with patient outcome, and its relationship with Human Papillomavirus (HPV)/p16(INK4A) status., Material and Methods: Copy number of the ATM gene and chromosome 11 were determined by FISH and HPV status was determined using p16(INK4A) immunohistochemistry in 87 paraffin embedded tumour samples from patients with HNSCC treated with chemoradiation at a single institution. ATM loss was correlated with patient outcome as both a continuous and dichotomous variable., Results: Of 73 evaluable patients, 44 (60.3%) demonstrated loss of the ATM gene. There was no correlation between ATM loss (defined as a mean ratio of ATM: chromosome 11<0.75) and overall survival (OS, p=0.67) or time to locoregional failure (TTLRF, p=0.72). Similarly, when evaluated as a continuous variable there was no significant relationship between ATM loss and patient outcome (OS, p=0.89; TTLRF, p=0.21). No significant relationship was found between p16(INK4A) status and ATM loss, for patient outcome. We found 35.6% (n=26) of patients demonstrated polysomy of chromosome 11 (defined as the presence of a mean >2.5 copies of chromosome 11) which was significantly associated with p16(INK4A) negative status (p=0.0004), but did not influence outcome., Conclusions: ATM loss is a frequent event in HNSCC, however it does not impact outcome after treatment with chemoradiation. Polysomy of chromosome 11 was significantly associated with p16(INK4A) negative status but also lacks prognostic significance., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Concurrent chemotherapy and radiotherapy (CRT) has become standard treatment for many patients with advanced head and neck squamous cell carcinoma (HNSCC). This has led to controversy concerning the role of neck dissection (ND) in this setting. The current debate is focused on N2-N3 disease and the ability of a clinical complete response to predict the absence of viable cells in the ND specimen. Proponents of a systematic planned ND argue that it improves regional control and possibly disease-specific survival. They assert that a clinical response does not predict the pathologic response, and that in the event of recurrence in the neck, a surgical salvage procedure is unlikely to succeed. Conversely, there are many arguments in favor of performing ND only for patients who have evidence of residual neck disease because of the very low probability of isolated neck recurrence following a complete response. Proponents argue that for complete responders, planned ND is associated with no survival benefit. As planned surgery will only benefit patients with residual disease in the neck alone, there is a high rate of unnecessary ND with its associated morbidity. Another question concerns the appropriate type of ND to be performed. Even if required after chemoradiation, selective ND is oncologically feasible with minimal morbidity. Lastly, robust data from a randomized trial demonstrating the superiority of one approach vs. the other are lacking. After conducting a review of recent literature on the subject, the authors conclude that planned ND is not necessary for patients with complete response because of the availability of improved diagnostic follow up modalities, and the increased sensitivity to CRT of HNSCC, particularly HPV associated tumors., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We describe a case of locally advanced unresectable squamous-cell carcinoma of the oropharynx in a young woman with Bloom's syndrome. She was treated with radical radiation therapy and concurrent chemotherapy (cisplatin and 5-flurouracil). She was unable to complete treatment due to the development of severe side effects: confluent mucositis, moist desquamating skin reaction, severe diarrhea and severe myelosupression with neutropenic sepsis. The limited relevant literature is presented. We conclude that chemotherapy should be used with extreme caution in Bloom's syndrome patients.

The bacteriological status of 286 primal cuts stored frozen in intervention stores in England, Scotland and Northern Ireland for between 18 and 216 weeks was assessed in two surveys carried out during 1993 (120 cuts) and 1994 (166 cuts). Overall the aerobic plate count at 25°C and the presumptive pseudomonad counts were <10(5)cm(2) on 269 (94%) and 273 (95·5%) of the cuts, respectively. Similarly the coliform and enterococcal counts were <10(3)cm(2) on 98·3% and 97·9% of the cuts, respectively. These findings suggest that the quality of dressing and butchery of the carcasses was of a generally satisfactory standard although on occasions there may have been suboptimum hygiene control during slaughter and butchery or some delay before freezing. The bacterial numbers were higher on average on the cuts obtained from the lower part of the carcass while there was a tendency for the number of aerobic spoilage organism to decrease slightly with increasing storage time. Evidence was obtained in the second survey which indicated differences between microbiological quality of meat coming from different boning plants although it was not possible to make a detailed evaluation of this point as the number of cuts available for sampling from each plant differed in each year.

Frozen minced beef was obtained from five commercial wholesale producers, and the aerobic plate count, and counts of coliforms, Escherichia coli type 1 and Staphylococcus aureus, determined. No E. coli O157:H7 or salmonellas were detected. The results were evaluated in relation to: (1) two earlier surveys involving fresh mince purchased from retail butchers and supermarkets in the UK (Roberts et al., 1980; Hudson et al., 1986); and (2) the standards set out in Annex II of the Minced Meat Directive 94/65/EC. In respect to the latter, none of the 99 samples of mince examined was unsatisfactory.

It has previously been demonstrated that glucocorticoid suppression of mitogen-induced lymphocyte activation is a function of mitogen dose. Glucocorticoids suppress lymphocyte activation more at low doses, which induce suboptimal lymphocyte activation, than at higher doses which are optimal for lymphocyte activation. This observation suggests that glucocorticoid suppression of lymphocyte activation might be greater than normal in disease states which are associated with depressed mitogen-induced lymphocyte activation. To test this hypothesis, lymphocytes from normal individuals and patients with cystic fibrosis were activated by a full range of concentrations of concanavalin A (Con A) in the presence or absence of dexamethasone. Con A activation of cystic fibrosis lymphocytes was markedly depressed compared to the activation of normal lymphocytes at all doses of Con A, but the suppressive effect of dexamethasone on the activation of normal and cystic fibrosis lymphocytes was the same. We conclude that glucocorticoid suppression of lymphocyte activation is more a function of mitogen dose than of the level of lymphocyte activation and is not necessarily greater than normal in disease states which are associated with depressed mitogen-induced lymphocyte activation.