Hisham M. Mehanna

Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region.

Little information has been reported on regional and time trends of human papillomavirus (HPV) prevalence rates of oropharyngeal cancer (OPC) and non‐OPC.

Refeeding syndrome: what it is, and how to prevent and treat it

Refeeding syndrome is a well described but often forgotten condition. No randomised controlled trials of treatment have been published, although there are guidelines that use best available evidence for managing the condition. In 2006 a guideline was published by the National Institute for Health and Clinical Excellence (NICE) in England and Wales. Yet because clinicians are often not aware of the problem, refeeding syndrome still occurs.1 This review aims to raise awareness of refeeding syndrome and discuss prevention and treatment. The available literature mostly comprises weaker (level 3 and 4) evidence, including cohort studies, case series, and consensus expert opinion.2 Our article also draws attention to the NICE guidelines on nutritional support in adults, with particular reference to the new recommendations for best practice in refeeding syndrome.3 These recommendations differ in parts from—and we believe improve on—previous guidelines, such as those of the Parenteral and Enteral Nutrition Group of the British Dietetic Association (box 1).4 #### Box 1 Why use the NICE guidelines on refeeding syndrome? Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally5). These shifts result …

A systematic review and meta‐analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy

Objectives:  This review examines the effectiveness of positron emission tomography (PET) in the detection of recurrent or persistent head and neck squamous cell carcinoma after radiotherapy or chemoradiotherapy.

Treatment and follow-up of oral dysplasia — A systematic review and meta-analysis†

The aim of this study was to inform an evidence‐based management policy for oral dysplastic lesions.

Head and neck cancer—Part 1: Epidemiology, presentation, and prevention

#### Summary points Head and neck cancers include cancers of the upper aerodigestive tract (including the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx), the paranasal sinuses, and the salivary glands. Cancers at different sites have different courses and variable histopathological types, although squamous cell carcinoma is by far the most common. The anatomical sites affected are important for functions such as speech, swallowing, taste, and smell, so the cancers and their treatments may have considerable functional sequelae with subsequent impairment of quality of life. Decisions about treatment are usually complex, and they must balance efficacy of treatment and likelihood of survival, with potential functional and quality of life outcomes. Patients and their carers need considerable support during and after treatment. #### Sources and selection criteria We used the terms “head and neck”, “larynx”, “oral”, and “oropharynx”—with each limited by “cancer”, “diagnosis”, and “treatment” separately—to search the Medline, Embase, PubMed, Cochrane, CINAHL, and AMED databases. We also used them to cross check national guidelines, reference lists, textbooks, and personal reference lists. We assessed over 1000 identified abstracts for relevance. In this first part of a two article series, we review the common presentations of head and neck cancer. We also discuss common investigations and new …

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients

BACKGROUND We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer

BACKGROUND The role of image-guided surveillance as compared with planned neck dissection in the treatment of patients with squamous-cell carcinoma of the head and neck who have advanced nodal disease (stage N2 or N3) and who have received chemoradiotherapy for primary treatment is a matter of debate. METHODS In this prospective, randomized, controlled trial, we assessed the noninferiority of positron-emission tomography-computed tomography (PET-CT)-guided surveillance (performed 12 weeks after the end of chemoradiotherapy, with neck dissection performed only if PET-CT showed an incomplete or equivocal response) to planned neck dissection in patients with stage N2 or N3 disease. The primary end point was overall survival. RESULTS From 2007 through 2012, we recruited 564 patients (282 patients in the planned-surgery group and 282 patients in the surveillance group) from 37 centers in the United Kingdom. Among these patients, 17% had nodal stage N2a disease and 61% had stage N2b disease. A total of 84% of the patients had oropharyngeal cancer, and 75% had tumor specimens that stained positive for the p16 protein, an indicator that human papillomavirus had a role in the causation of the cancer. The median follow-up was 36 months. PET-CT-guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 vs. 221); rates of surgical complications were similar in the two groups (42% and 38%, respectively). The 2-year overall survival rate was 84.9% (95% confidence interval [CI], 80.7 to 89.1) in the surveillance group and 81.5% (95% CI, 76.9 to 86.3) in the planned-surgery group. The hazard ratio for death slightly favored PET-CT-guided surveillance and indicated noninferiority (upper boundary of the 95% CI for the hazard ratio, <1.50; P=0.004). There was no significant difference between the groups with respect to p16 expression. Quality of life was similar in the two groups. PET-CT-guided surveillance, as compared with neck dissection, resulted in savings of £1,492 (approximately

Oropharyngeal carcinoma related to human papillomavirus

2,190 in U.S. dollars) per person over the duration of the trial. CONCLUSIONS Survival was similar among patients who underwent PET-CT-guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective. (Funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK; PET-NECK Current Controlled Trials number, ISRCTN13735240.).

Biomarkers in dysplasia of the oral cavity: A systematic review

Incidence is increasing rapidly, with implications for prognosis and policy

Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24

Oral dysplasia is a potentially precancerous lesion diagnosed histologically. While the risk of progression is associated with histological grade, it is currently impossible to predict accurately which lesions will progress. More accurate markers predicting progression to cancer would enable the targeting of these lesions for more aggressive treatment and closer follow-up. We have performed a systematic review with pooling of data to assess the evidence for the use of biomarkers in predicting transformation of oral dysplasia into cancer. We systematically searched the Cochrane library, MEDLINE, EMBASE, AMED, Cinahl and the Kings Fund electronic databases using the terms: oral dysplasia, leukoplakia, erythroplakia, biomarkers and genetic markers. The following a priori selection criteria were used: longitudinal cohort or case-controlled studies of oral dysplasia that progressed to cancer. Cross-sectional studies and studies reporting only on leukoplakia were excluded. Data were extracted by two reviewers. Quality assessment was carried out using validated tools. We assessed the relative risk of progression form oral dysplasia to cancer and pooled data where possible. 2550 studies were identified, from which 288 were scrutinised in greater detail. Of these, 247 were excluded, mainly due to cross-sectional design. Of the 41 studies containing follow-up data, 28 were excluded, most commonly due to data only being available for lesions once they had progressed to cancer. A lack of clear histological definition of oral lesions was also a common finding. Data were extracted from 13 longitudinal studies. The evidence consists mainly of small, single centre, retrospective studies. In oral dysplasia, loss of heterozygosity (LOH), particularly at the 3p+/-9p loci, increases the risk of progression to cancer (RR 17.60 (2.77, 108.37) p<0.001), as does survivin (RR 30 (4.25, 197.73), p0.001), matrix metalloproteinase (MMP 9), (RR 19.00 (1.56, 209.38) p=0.02) and DNA content (RR 12.00 (1.17, 82.10) p=0.03). Other markers identified by this review including p53, p73, MMP 1 and 2 and cathepsin L mRNA, did not predict progression. LOH, survivin, MMP 9 and DNA content are potential markers for increased risk of progression from oral dysplasia to cancer. Many methodological limitations have been identified by this review, however, and we recommend these results are interpreted with caution. Research into this field should concentrate on longitudinal design, with pooling of data from multiple centres to achieve larger cohorts. We recommend standardisation of definitions to allow appropriate comparisons to be made.