The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. Cancer Research UK.

Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

P16^INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0·744, p=0·0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5-82·7) for p16+/HPV+, 40·4% (38·6-42·4) for p16-/HPV-, 53·2% (46·6-60·8) for p16-/HPV+, and 54·7% (49·2-60·9) for p16+/HPV-. 5-year disease-free survival was 84·3% (95% CI 82·9-85·7) for p16+/HPV+, 60·8% (58·8-62·9) for p16-/HPV-; 71·1% (64·7-78·2) for p16-/HPV+, and 67·9% (62·5-73·7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. European Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and the Stockholm Cancer Society.

To study the effectiveness of Type 1 tympanoplasty for chronic tympanic membrane perforations in the pediatric age group and to investigate factors influencing its success. Searches were conducted of the MEDLINE database and the Cochrane Database of Systematic Reviews using terms focused around tympanoplasty and children. Searches were performed on June 23, 2014 and limited to English language entries since January 1, 1997. Studies reporting tympanoplasty closure rates in children 18 years and younger, with a minimum follow-up of 6 months, were included. Studies focusing on more advanced forms of tympanoplasty and revision surgery were excluded. Five hundred sixty-four articles were screened identifying 2,609 cases from 45 eligible studies. Data were collected by consensus of the first two authors with the third author arbitrating disparities of opinion. Success was taken as the closure rate at 12 months where possible. Forest plots with Mantel-Haenszel analyses were used to compare closure rates with respect to perforation size, adenoidectomy, status of contralateral ear, Eustachian tube function, active infection, and graft position. Linear regression and Fisher's exact were used to analyze closure rate with respect to age. The mean weighted closure rate for pediatric tympanoplasty was 83.4%. Subgroup analysis found age not to be a significant factor affecting the closure rate. Tympanoplasties performed on larger perforations or in children with abnormal contralateral ear findings were more likely to fail. Surgery may be best delayed until contralateral otitis media with effusion has settled.

Refeeding syndrome is an important, yet commonly overlooked condition affecting patients. It occurs when feeding is commenced after a period of starvation. Head and neck cancer patients are at particular risk owing to prolonged periods of poor nutritional intake. This may be from general effects such as cancer anorexia or from more specific problems of dysphagia associated with this group of patients. Awareness of the condition is crucial in identifying patients at risk and taking measures to prevent its occurrence. The aims of this review are to: 1) Highlight the condition and stress the importance of its consideration when admitting head and neck cancer patients. 2) Discuss the pathophysiology behind refeeding syndrome. 3) Review the literature for the best available evidence and guidelines. 4) Highlight the need for further high quality research. Refeeding syndrome is potentially fatal, yet is preventable. Awareness and identification of at-risk patients is crucial to improving management. Refeeding syndrome is caused by rapid refeeding after a period of under-nutrition, characterised by hypophosphataemia, electrolyte shifts and has metabolic and clinical complications. High risk patients include the chronically under-nourished and those with little intake for greater than 10 days. Patients with dysphagia are at particular risk. Refeeding should commence at 10 kcal/kg per day in patients at risk, and increased slowly. Thiamine, vitamin B complex and multi-vitamin supplements should be started with refeeding. New NICE guidelines state that pre-feeding correction of electrolyte and fluid deficits is unnecessary, but should be done concurrently with re-feeding. More research in this field is needed as the evidence base is lacking.

The use of transoral robotic surgery (TORS) and laser microsurgery (TLM) in the diagnosis and identification of the site of the unknown primary has become increasingly common. This systematic review and meta-analysis aims to assess the use and efficacy of TORS and TLM for this indication. Systematic review and meta-analysis of studies employing TORS or TLM in diagnosis of the unknown primary tumor site in patients with cervical nodal metastases of squamous cell origin. MEDLINE, EMBASE and CINHAL were searched from inception to July 2018 for all studies that used TORS and or TLM in identifying the unknown primary. 251 studies were identified, of which 21 were eligible for inclusion. The primary tumour was identified by TORS/TLM in 78% of patients (433 out of 556). Tongue base mucosectomy (TBM) identified the primary in 222 of 427 cases (53%). In patients with negative physical examination, diagnostic imaging and PETCT, TBM identified the primary in 64% (95% CI 50, 79) cases. In patients who had negative CT/MRI imaging, negative PETCT and negative EUA and tonsillectomy, TBM identified a tongue base primary in 78% (95% CI 41, 92) cases. Haemorrhage, the commonest complication, was reported in 4.9% cases. Mean length of stay varied between 1.4 and 6.3 days. Tongue base mucosectomy, performed by TORS or TLM, is highly efficacious in identifying the unknown primary in the head and neck region.