Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex.

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.

What factors influence refugees' attendance to dental care services?

DATA SOURCES: Four electronic databases: MEDLINE (via Ovid), Embase (via Ovid), Web of Science, and American Psychology Association PsycINFO. STUDY SELECTION: Quantitative observational or interventional studies, published until the end of February 2022 with no restrictions to date, language, or region of publication. DATA EXTRACTION AND SYNTHESIS: Screening performed by one author and a second author independently reviewed a random sample of 10% of the articles. Disagreements were resolved in consultation with a third author. RESULTS: The results were presented as a narrative review due to large heterogeneity of data. Nine studies met the eligibility criteria and most of them were rated as fair quality. The main factors influencing refugees access to dental care services were demographic and socioeconomic characteristics and English language proficiency. CONCLUSIONS: The review suggests that individual-level factors may have a predisposing effect on refugees' access, but had limited evidence on other enabling and contextual factors.

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007. OBJECTIVES: To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 9 February 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared two or more surgical treatment modalities, or surgery versus other treatment modalities, for primary tumours of the oral cavity or oropharynx. DATA COLLECTION AND ANALYSIS: Our primary outcomes were overall survival, disease-free survival, locoregional recurrence, and recurrence; and our secondary outcomes were adverse effects of treatment, quality of life, direct and indirect costs to patients and health services, and participant satisfaction. We used standard Cochrane methods. We reported survival data as hazard ratios (HRs). For overall survival, we reported the HR of mortality, and for disease-free survival, we reported the combined HR of new disease, progression, and mortality; therefore, HRs below 1 indicated improvement in these outcomes. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified four new trials, bringing the total number of included trials to 15 (2820 participants randomised, 2583 participants analysed). For objective outcomes, we assessed four trials at high risk of bias, three at low risk, and eight at unclear risk. The trials evaluated nine comparisons; none compared different surgical approaches for excision of the primary tumour. Five trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Elective ND compared with therapeutic ND probably improves overall survival (HR 0.64, 95% confidence interval (CI) 0.50 to 0.83; I2 = 0%; 4 trials, 883 participants; moderate certainty) and disease-free survival (HR 0.56, 95% CI 0.45 to 0.70; I2 = 12%; 5 trials, 954 participants; moderate certainty), and probably reduces locoregional recurrence (HR 0.58, 95% CI 0.43 to 0.78; I2 = 0%; 4 trials, 458 participants; moderate certainty) and recurrence (RR 0.58, 95% CI 0.48 to 0.70; I2 = 0%; 3 trials, 633 participants; moderate certainty). Elective ND is probably associated with more adverse events (risk ratio (RR) 1.31, 95% CI 1.11 to 1.54; I2 = 0%; 2 trials, 746 participants; moderate certainty). Two trials evaluated elective radical ND versus elective selective ND in people with oral cavity cancer, but we were unable to pool the data as the trials used different surgical procedures. Neither study found evidence of a difference in overall survival (pooled measure not estimable; very low certainty). We are unsure if there is a difference in effect on disease-free survival (HR 0.57, 95% CI 0.29 to 1.11; 1 trial, 104 participants; very low certainty) or recurrence (RR 1.21, 95% CI 0.63 to 2.33; 1 trial, 143 participants; very low certainty). There may be no difference between the interventions in terms of adverse events (1 trial, 148 participants; low certainty). Two trials evaluated superselective ND versus selective ND, but we were unable to use the data. One trial evaluated supraomohyoid ND versus modified radical ND in 332 participants. We were unable to use any of the primary outcome data. The evidence on adverse events was very uncertain, with more complications, pain, and poorer shoulder function in the modified radical ND group. One trial evaluated sentinel node biopsy versus elective ND in 279 participants. There may be little or no difference between the interventions in overall survival (HR 1.00, 95% CI 0.90 to 1.11; low certainty), disease-free survival (HR 0.98, 95% CI 0.90 to 1.07; low certainty), or locoregional recurrence (HR 1.04, 95% CI 0.91 to 1.19; low certainty). The trial provided no usable data for recurrence, and reported no adverse events (very low certainty). One trial evaluated positron emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (before or after chemoradiotherapy) in 564 participants. There is probably no difference between the interventions in overall survival (HR 0.92, 95% CI 0.65 to 1.31; moderate certainty) or locoregional recurrence (HR 1.00, 95% CI 0.94 to 1.06; moderate certainty). One trial evaluated surgery plus radiotherapy versus radiotherapy alone and provided very low-certainty evidence of better overall survival in the surgery plus radiotherapy group (HR 0.24, 95% CI 0.10 to 0.59; 35 participants). The data were unreliable because the trial stopped early and had multiple protocol violations. In terms of adverse events, subcutaneous fibrosis was more frequent in the surgery plus radiotherapy group, but there were no differences in other adverse events (very low certainty). One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 participants. There may be little or no difference between the interventions for overall survival (HR 0.83, 95% CI 0.09 to 7.46; low certainty) or disease-free survival (HR 1.07, 95% CI 0.27 to 4.22; low certainty). For adverse events, there were too many outcomes to draw reliable conclusions. One trial evaluated surgery plus adjuvant radiotherapy versus chemotherapy. We were unable to use the data for any of the outcomes reported (very low certainty). AUTHORS' CONCLUSIONS: We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.

The COVID-19 pandemic has not changed stage at presentation nor treatment patterns of head and neck cancer: A retrospective cohort study.

OBJECTIVES: To evaluate the impact of the COVID-19 lockdown measures on HNC, by comparing the stage at presentation and treatment of HNC before and after the most severe COVID-19 restrictions. DESIGN: A retrospective cohort study. SETTING: A regional cancer network serving a patient population of 2.4 million. PARTICIPANTS: Newly diagnosed patients with HNC between June and October 2019 (pre-pandemic) and June and October 2021 (post-pandemic). MAIN OUTCOME MEASURES: Symptom duration before diagnosis, stage at diagnosis, patient performance status (PS) and intent of treatment delivered (palliative vs. curative). RESULTS: Five hundred forty-five patients were evaluated-250 in the 2019 and 295 in the 2021 cohort. There were no significant differences in symptom duration between the cohorts (p = .359) or patient PS (p = .821). There were no increased odds of presenting with a late (Stage III or IV) AJCC cancer stage in 2021 compared with 2019 (odds ratio [OR] = 0.90; 95% confidence interval [CI]: 0.76-1.08); nor increased odds of receiving palliative rather than curative treatment in 2021 compared with 2019 (OR = 0.68; 95% CI: 0.45-1.03). CONCLUSION: The predicted stage shift to more advanced disease at the time of diagnosis of HNC due to the COVID-19 pandemic has not been realised in the longer term. In keeping with this, there was no difference in symptom duration, patient PS, or treatment patterns between the 2019 and 2021 cohorts.

Systematic overview of systematic reviews and clinical guidelines: assessment and prevention of behavioural risk factors associated with oral cancer to inform dental professionals in primary care dental practices.

Aims/objectives Tobacco and alcohol are recognised as the major modifiable risk factors for oral cancer, the incidence of which is rising globally and predicted to increase. This paper aimed to: 1) appraise and synthesise best practice evidence for assessing the major behavioural risk factors for oral cancer and delivering behaviour change interventions (for example, advice, counselling, signposting/referral to preventive services); and 2) assess appropriateness for implementation by dental professionals in primary care.Methods A systematic overview was undertaken of systematic reviews and international clinical guidelines. This involved: systematically searching and collating the international literature on assessing oral cancer risk and delivering preventive interventions within primary care; quality appraising and assessing the risk of bias using validated tools; synthesising the evidence for best practice; and assessing application of key findings to the dental setting.Results and conclusions There is clear evidence for the effectiveness of a 'brief', in-person, motivational intervention for sustained tobacco abstinence or reduced alcohol consumption, following risk factor assessment. Evidence for combined behavioural interventions is lacking. There is no firm conclusion with regards to optimal duration of brief interventions (range 5-20 minutes). For tobacco users, longer (10-20 minutes) and intensive (more than 20 minutes, with follow-up visits) interventions are more effective in increasing quit rates compared to no intervention; very brief (less than five minutes) interventions in a single session show comparable effectiveness to the longer/more intensive interventions. For alcohol users, 10-15-minute multi-contact interventions were most effective, compared to no intervention or very brief (less than five minutes) intervention or intensive intervention; brief interventions of five-minute duration were equally effective. There is limited direct evidence from the dental practice setting (one high-quality systematic review relating to tobacco prevention and none relating to alcohol). Thus, very brief, or brief advice of up to five minutes, should be trialled for tobacco and alcohol respectively in a dental practice setting, after risk assessment tailored to patient motivational status. Exploring delivery by the dental team is supported, as effectiveness was generally independent of primary care provider.

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.

BACKGROUND: Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011. OBJECTIVES: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting. SEARCH METHODS: An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration. DATA COLLECTION AND ANALYSIS: For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary. MAIN RESULTS: We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.  For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence).  There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence). Primary treatment with CRT, as compared to radiotherapy alone,  was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence).  AUTHORS' CONCLUSIONS: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The  evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.

Lessons learned from the INHANCE consortium: An overview of recent results on head and neck cancer.

OBJECTIVE: To summarize the latest evidence on head and neck cancer epidemiology from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. SUBJECTS AND METHODS: INHANCE was established in 2004 to elucidate the etiology of head and neck cancer through pooled analyses of individual-level data on a large scale. We summarize results from recent INHANCE-based publications updating our 2015 overview. RESULTS: Seventeen papers were published between 2015 and May 2020. These studies further define the nature of risks associated with tobacco and alcohol, and occupational exposures on head and neck cancer. The beneficial effects on incidence of head and neck cancer were identified for good oral health, endogenous and exogenous hormonal factors, and selected aspects of diet related to fruit and vegetables. INHANCE has begun to develop risk prediction models and to pool follow-up data on their studies, finding that ~30% of cases had cancer recurrence and 9% second primary cancers, with overall- and disease-specific 5-year-survival of 51% and 57%, respectively. CONCLUSIONS: The number and importance of INHANCE scientific findings provides further evidence of the advantages of large-scale internationally collaborative projects and will support the development of prevention strategies.

A systematic review of interventions to link families with preschool children from healthcare services to community-based support.

BACKGROUND: Supporting patients to access community-based support may be a key intervention to address the wider determinants of health. There is a lack of evidence synthesis around the most effective methods for linking individuals from health services to organizations within communities, especially those aimed at supporting families with young children. METHODS: Papers were identified from seven databases covering peer-reviewed and grey literature. The Effective Public Health Practice Project and the Critical Appraisal Skills Programme Qualitative quality appraisal tools were used to assess methodological quality. Thematic narrative data synthesis based on study quality was performed. RESULTS: Twenty-four unique publications were included in the review with a range of study designs and variable methodological quality. A broad typology of intervention processes for undertaking linking was developed defining three distinct approaches: signposting, referral and facilitation. Active processes, such as facilitation, appeared more successful at linking families to community support. CONCLUSIONS: This was the first systematic review to focus on interventions that link families with young children to community-based support organizations. It identified a typology for linking interventions, and whilst there were limitations in the quality of evidence available, it showed a tendency for more active interventions to be more effective in linking families to community support.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Fluoride Varnish in Nursery Schools: A Randomised Controlled Trial - Protecting Teeth @3.

Studies suggest that fluoride varnish (FV) application can reduce dental caries in child populations. The multiple-component national child oral health improvement programme in Scotland (Childsmile) includes nursery-based universal supervised toothbrushing and deprivation-targeted FV applications, together with community and dental practice prevention interventions. This trial, a double-blind, two-arm randomised control trial, aimed to assess the effectiveness and cost-effectiveness of the nursery-based FV applications plus treatment-as-usual (TAU) Childsmile programme interventions, compared to TAU Childsmile interventions alone, in children not targeted to receive nursery FV as part of the programme. Participating children in the first year of nursery (aged three), with or without existing caries, were randomised to either FV or TAU and followed up for 24 months until the first year of primary school. Treatments were administered at six-monthly intervals. The primary endpoint was "worsening of d3mft" from baseline to 24 months. Secondary endpoints were worsening of d3mfs, d3t, mt, and ft. Individual record-linkage captured wider programme activities and tertiary endpoints. A total of 1,284 children were randomised, leading to 1,150 evaluable children (n = 577 FV, n = 573 TAU, 10% dropouts). Mean age was 3.5 years, 50% were female (n = 576), 17% had caries at baseline (n = 195), all balanced between the groups. Most children received three/four treatments. Overall, 26.9% (n = 155) had worsened d3mft in the FV group, and 31.6% (n = 181) in the TAU group, with an odds ratio (OR) of 0.80 (0.62-1.03), p = 0.078. The results for worsening of the secondary endpoints were: d3mfs 0.79 (0.61-1.01) p = 0.063, d3t 0.75 (0.57-0.99) p = 0.043, mt 1.34 (0.75-2.39) p = 0.319, and ft 0.77 (0.53-1.14) p = 0.191. We calculated a number needed to treat of 21 and a cost of GBP 686 to prevent a single worsening of d3mft. There was a modest non-significant reduction in the worsening of d3mft in the nursery FV group compared to TAU, suggesting that this intervention is unlikely to represent an effective or cost-effective addition to the population oral health improvement programme.

Exploring the cost-effectiveness of child dental caries prevention programmes. Are we comparing apples and oranges?

Data sources The following seven databases were searched: PubMed, EMBASE, DARE, NHSEED, HTA, Cost-Effectiveness Analysis Registry and Paediatric Economic Database Evaluation (PEDE).Study selection The review included trial and model-based economic evaluation studies and the participants included children aged from 0 to 12 years old who were healthy except for having dental caries. Studies of mixed populations of parents and children were included where the data for children were presented separately.The interventions included were:• Community-based oral-health education/training programs related to healthy oral habits.• Screening of children's teeth.• Supervised toothbrushing technique through the provision of toothbrushes, an appropriate amount of fluoride toothpaste, and topical fluoride.• Advice on dietary control, such as limitation of sugar or carbohydrates consumption, and enhanced fortified nutrition with an appropriate amount of calcium intake.• The comparators were situations where the populations were the same as the test group, but were receiving no intervention, or a dissimilar one .The interventions were oral-health promotion programs (OHPPs) implemented by oral-health professionals in the contexts of home visits, telephone calls, healthcare centres and primary schools.The outcome measures were reductions in the Decayed, Missing, Filled Teeth (DMFT) index for permanent teeth or (dmft) index for deciduous teeth among children and OHPP cost, incremental cost (difference between mean costs of intervention and mean costs of the comparator), and cost-effectiveness analysis (CEA).Data extraction and synthesis The title, abstract and full text of each study were screened. During the first phase screening of titles and abstracts, irrelevant records were removed. The exclusion criteria were: participant with health-related diseases or aged older than 12 years; interventions other than OHPP (such as implant dentistry or other invasive-dentistry programs); other economic-evaluation outcomes such as cost-benefit, cost-utility or cost-minimisation; authors' opinion (unoriginal records); reviews; and study language other than English. The second-phase screening assessed full texts of the articles using the same eligibility criteria. The risk of bias was assessed using the Drummond 10-item Checklist. Meta-analysis: The costs were converted to 2015 USA dollars. Data analysis was performed through dichotomous outcomes such as the number of children in the intervention and in the control group, the DMFT index in children, and the OHPP cost. Odds ratios (ORs), effect sizes with 95% confidence interval (CIs) and study weights were estimated from random effects analysis. Forest plots were constructed for each outcome, and chi-square tests used to assess homogeneity, where a p-value of less than 0.1 indicated statistically significant heterogeneity. An I2 test was used to quantify inconsistencies between studies as the percentage of variation across studies. Data synthesis was carried out using narrative demonstration, with a summary of the characteristics of each included study. For quantitative synthesis, a summary of the combined estimation related to the OHPP effect was measured. Three types of subgroup analysis were performed: by the age of the children (age under or equal to 6 years, and age 6-12 years), by publication year (studies published in the last five years, and earlier published studies) and by the country of the study. Egger's regression test and a funnel plot were used to assess and demonstrate publication bias. Publication bias was considered present if the p-value of the Egger test was more than 0.05.Results 19 full texts were included into qualitative synthesis and eight articles used in quantitative synthesis. Qualitative synthesis results: With regards to the country of origin, 32% of the studies were conducted in the United Kingdom (n = 6), 26% in Australia (n = 5), 16% in the United States (n = 3). There was also one study from each of the following countries Finland, Ireland, Japan, Nigeria and Singapore. Fifty-two percent (n = 10) were model-based economic evaluation studies and 47% (n = 9) were trial-based economic evaluations. The population of 14 studies were younger than six years of age, while in four studies the children were over the age of six years. In one paper the age of the children was not clearly stated. Just under a half of the papers (47%) were published in the last five years.The majority of the studies had a low risk of bias (n = 12, 63%) and seven (37%) had a moderate risk of bias. Various outcome measures were used in the included studies: DMFT, average number of dental visits, number of prevented caries teeth, average number of cavity-free months, probability of less cost, caries prevalence, number of specific OHPP visits, quality-adjusted life year, cost-effectiveness ratio, and percentages of not having debris.Quantitative synthesis results: The overall pooled impact of OHPPs showed that children with tooth decay had 81% lower odds of participating in OHPP (95% CI 61-90%, I2: 98.5%, p = 0) with considerable heterogeneity among studies. OHPPs were successful in reducing financial costs in 97 out of 100 OHPPs (95% CI 89-99%, I2: 99%, p = 0) with considerable heterogeneity among studies. The studies with participants under the age of six years old weighted 71% with an OR of 0.14 (95% CI, 0.05-0.39, I2: 99%). These children had the highest benefit of OHPPs to lower DMFT/S. The studies reporting children aged six years and over weighted 29% with an OR of 0.29 (95% CI, 0.08-1.01, I2: 99%), and these children had no benefit from OHPPs in lowering DMFT/S. Studies with under-six-year-old participants had an OR of 0.07 (95% CI, 0.02-0.32) revealing no cost-effectiveness effect to reduce OHPP incremental cost, whereas studies reporting children aged six years and older had an OR of 0.0 (95% CI, 0.00-48,704.6). The authors concluded that OHPPs involving the later (older) children were cost-effective in reducing the OHPPs' incremental cost.Conclusions A comprehensive analysis of the OHPPs confirmed that DMFT could be reduced, hence, lowering the financial burden of dental-care treatment. More effort is needed to manage the allocation of scarce resources, taking into account the economic impact of dental caries on healthcare systems. More studies on caries-prevention programmes among young children in high-, middle- and low-income countries are needed, in order to assess the clinical and financial effectiveness.

Another oral cancer clinical guideline - but does it propose changes to dental practice?

Scope and purpose This guideline concerns patients with no lesions, innocuous or nonsuspicious lesions, lesions suspected to be potentially malignant as well as malignant lesions of the oral cavity. The audience for this guideline is health care workers who examine the mouth as well as community dental health co-ordinators and policy makers. Methodology The Appraisal of Guidelines Research & Evaluation reporting checklist II and the GIN-McMaster Guideline Development Checklist were followed and the guideline is partly informed by systematic reviews and diagnostic test accuracy meta-analyses. Studies assessing patients' values and preferences were also considered. The process of moving from the evidence to decisions and the formulation was guided by GRADE (Grading of Recommendations Assessment, Development and Evaluation).Review and Updating Updates for this guideline will be conducted every five years or when new emerging evidence indicates a potential change in the recommendation statements from the expert panel. Any updated versions of this guideline will be available at the ADA Center for Evidence-Based Dentistry's website: www.ebd.ada Recommendations The expert panel developed six conditional recommendations, all based on evidence rated as low to very low quality using GRADE. 1. For patients with a clinically evident oral mucosal lesion with an unknown clinical diagnosis considered to be seemingly innocuous or nonsuspicious of malignancy, or other symptoms, clinicians should follow up periodically to determine the need for further evaluation. If the lesion has not resolved and the clinical diagnosis of a potentially malignant disorder cannot be ruled out, then clinicians should perform a biopsy of the lesion or refer the patient to a specialist.2. For patients with a clinically evident oral mucosal lesion considered to be suspicious of a potentially malignant or malignant disorder, or other symptoms, clinicians should perform a biopsy of the lesion or provide immediate referral to a specialist.3. Cytologic adjuncts for the evaluation of potentially malignant disorders among adult patients with clinically evident, seemingly innocuous or suspicious lesions are not recommended. Should a patient decline the clinician's recommendation for performing a biopsy of the lesion or referral to a specialist, the clinician can use a cytologic adjunct to provide additional lesion assessment. A positive or atypical cytologic test result reinforces the need for a biopsy or referral.A negative cytologic test result indicates the need for periodic follow-up of the patient. If the clinician detects persistence or progression of the lesion, immediately performing a biopsy of the lesion or referral to a specialist is indicated.4. The panel does not recommend autofluorescence, tissue reflectance or vital staining adjuncts for the evaluation of potentially malignant disorders among adult patients with clinically evident, seemingly innocuous or suspicious lesions.5. The panel suggests that for patients with no clinically evident lesions or symptoms, no further action is necessary at that time.6. The panel does not recommend commercially available salivary adjuncts for the evaluation of potentially malignant disorders among adult patients with or without clinically evident, seemingly innocuous or suspicious lesions and their use should be considered only in the context of research.Research recommendations There is a need for better estimation of the prevalence of potentially malignant disorders (PMDs) and oral squamous cell carcinoma (OSCC) in populations with different baseline risks. More information on patients' values and preferences is required as well as studies on the diagnostic test accuracy of cytologic and salivary adjuncts.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early-stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. This is an update of a review originally published in 2007 and first updated in 2011. OBJECTIVES: To determine which surgical treatment modalities for oral and oropharyngeal cancers result in increased overall survival, disease-free survival and locoregional control and reduced recurrence. To determine the implication of treatment modalities in terms of morbidity, quality of life, costs, hospital days of treatment, complications and harms. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE Ovid (1946 to 20 December 2017) and Embase Ovid (1980 to 20 December 2017). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on the language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, or where separate data could be extracted for these participants, and that compared two or more surgical treatment modalities, or surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Two or more review authors independently extracted data and assessed risk of bias. We contacted study authors for additional information as required. We collected adverse events data from included studies. MAIN RESULTS: We identified five new trials in this update, bringing the total number of included trials to 12 (2300 participants; 2148 with cancers of the oral cavity). We assessed four trials at high risk of bias, and eight at unclear. None of the included trials compared different surgical approaches for the excision of the primary tumour. We grouped the trials into seven main comparisons.Future research may change the findings as there is only very low-certainty evidence available for all results.Five trials compared elective neck dissection (ND) with therapeutic (delayed) ND in participants with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate in most cases. Four of these trials reported overall and disease-free survival. The meta-analyses of two trials found no evidence of either intervention leading to greater overall survival (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.41 to 1.72; 571 participants), or disease-free survival (HR 0.73, 95% CI 0.25 to 2.11; 571 participants), but one trial found a benefit for elective supraomohyoid ND compared to therapeutic ND in overall survival (RR 0.40, 95% CI 0.19 to 0.84; 67 participants) and disease-free survival (HR 0.32, 95% CI 0.12 to 0.84; 67 participants). Four individual trials assessed locoregional recurrence, but could not be meta-analysed; one trial favoured elective ND over therapeutic delayed ND, while the others were inconclusive.Two trials compared elective radical ND with elective selective ND, but we were unable to pool the data for two outcomes. Neither study found evidence of a difference in overall survival or disease-free survival. A single trial found no evidence of a difference in recurrence.One trial compared surgery plus radiotherapy with radiotherapy alone, but data were unreliable because the trial stopped early and there were multiple protocol violations.One trial comparing positron-emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (either before or after chemoradiotherapy), showed no evidence of a difference in mortality (HR 0.92, 95% CI 0.65 to 1.31; 564 participants). The trial did not provide usable data for the other outcomes.Three single trials compared: surgery plus adjunctive radiotherapy versus chemoradiotherapy; supraomohyoid ND versus modified radical ND; and super selective ND versus selective ND. There were no useable data from these trials.The reporting of adverse events was poor. Four trials measured adverse events. Only one of the trials reported quality of life as an outcome. AUTHORS' CONCLUSIONS: Twelve randomised controlled trials evaluated ND surgery in people with oral cavity cancers; however, the evidence available for all comparisons and outcomes is very low certainty, therefore we cannot rely on the findings. The evidence is insufficient to draw conclusions about elective ND of clinically negative neck nodes at the time of removal of the primary tumour compared to therapeutic (delayed) ND. Two trials combined in meta-analysis suggested there is no difference between these interventions, while one trial (which evaluated elective supraomohyoid ND) found that it may be associated with increased overall and disease-free survival. One trial found elective ND reduced locoregional recurrence, while three were inconclusive. There is no evidence that radical ND increases overall or disease-free survival compared to more conservative ND surgery, or that there is a difference in mortality between PET-CT surveillance following chemoradiotherapy versus planned ND (before or after chemoradiotherapy). Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of people undergoing different surgical treatments.

Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer.

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.