Experience of Managing Head and Neck Cancer Patients Amongst Specialty Trainees in Restorative Dentistry

Background: Upon completion of Specialty Training in Restorative Dentistry, trainees (StRs) should
be proficient in maxillofacial prosthodontics to meet the restorative needs of head and neck cancer patients (HANC), and in preparation for the Intercollegiate Specialty Fellowship Examination (ISFE).1,2
Objective: The aim of this study is to collate and compare data relating to the training of Restorative Dentistry Rs in the management of HANC patients across different geographical locations within the British Isles. Methods: Current trainees were invited to complete an online questionnaire by the Specialty Registrars in Restorative Dentistry Group (SRRDG). Participants were asked to rate their confidence and experience in assessing and planning treatment for HANC patients, attending theatre and manufacturing surgical obturators, and in providing implants for appropriate cases. Respondents were also asked to appraise clinical and didactic teaching within their unit, and to rate their confidence of passing oncology- based questions in a future ISFE. Results: Responses were obtained from 21 StRs (n=21) training in all five countries within the British Isles. Most respondents were based in England (76%). A third were in their 5th year of training. Less than half reported that they were confident
of independently assessing (48%) or treatment planning (38%) HANC patients. More than half of StRs (52%) indicated that they were not confident of attending theatres alone and manufacturing a surgical obturator. One third (33%) rated their experience of treating oncology patients with implants as poor or very poor, including three in their 5th year of training. Less than one third rated didactic teaching in maxillofacial prosthodontics at their unit as good or excellent. Only 4 respondents indicated that they were confident of answering an ISFE oncology question on management of healthcare delivery. Six StRs expressed concerns over a lack of case-based exposure.
Conclusion: Experience and training in maxillofacial prosthodontics is inconsistent for StRs across the British Isles with many lacking in clinical exposure.

POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer

HOX genes are master regulators of organ morphogenesis and cell differentiation during embryonic development, and continue to be expressed throughout post-natal life. To test the hypothesis that HOX genes are dysregulated in head and neck squamous cell carcinoma (HNSCC) we defined their expression profile, and investigated the function, transcriptional regulation and clinical relevance of a subset of highly expressed HOXD genes. Two HOXD genes, D10 and D11, showed strikingly high levels in HNSCC cell lines, patient tumor samples and publicly available datasets. Knockdown of HOXD10 in HNSCC cells caused decreased proliferation and invasion, whereas knockdown of HOXD11 reduced only invasion. POU2F1 consensus sequences were identified in the 5' DNA of HOXD10 and D11. Knockdown of POU2F1 significantly reduced expression of HOXD10 and D11 and inhibited HNSCC proliferation. Luciferase reporter constructs of the HOXD10 and D11 promoters confirmed that POU2F1 consensus binding sites are required for optimal promoter activity. Utilizing patient tumor samples a significant association was found between immunohistochemical staining of HOXD10 and both the overall and the disease-specific survival, adding further support that HOXD10 is dysregulated in head and neck cancer. Additional studies are now warranted to fully evaluate HOXD10 as a prognostic tool in head and neck cancers.

Specialty Registrars’ Experience of Managing Head and Neck Cancer Patients

Objective The aim of this study was to collate and compare data on the training of Specialty Registrars in Restorative Dentistry (StRs) in the management of head and neck cancer (HANC) patients across different training units within the UK and Ireland. Methods Current trainees were invited to complete an online questionnaire by the Specialty Registrars in Restorative Dentistry Group (SRRDG). Participants were asked to rate their confidence and experience of assessing and planning treatment for HANC patients, attending theatre alone and manufacturing surgical obturators, and providing implants for appropriate cases. Respondents were also asked to appraise clinical and didactic teaching at their unit, and to rate their confidence of passing a future Intercollegiate Specialty Fellowship Examination (ISFE)-station assessing knowledge of head and neck cancer. Results Responses were obtained from 21 StRs (n=21) training within all five countries of the British Isles. Most respondents were based in England (76%), with one StR in each of Scotland, Wales, Northern Ireland and the Republic of Ireland. A third (33%) were in their 5th year of training. Almost half of the StRs indicated that they were confident of independently assessing (48%) new patients with HANC, with fewer numbers reporting confidence in treatment planning (38%). The majority (52%) of respondents indicated that they were not confident of attending theatre alone and manufacturing a surgical obturator. A third (33%) rated their experience of treating HANC patients with implants as ‘poor’ or ‘very poor’, including three StRs in their 5th year of training. Less than one third (<33%) rated didactic teaching in maxillofacial prosthodontics at their unit as ‘good’ or ‘excellent’, and only 7 StRs indicated that they were confident of passing an ISFE-station focused on HANC. Conclusion Experience and training regarding patients with head and neck cancer is inconsistent for StRs across the UK and Ireland with a number of trainees reporting a lack of clinical exposure.

Coffee and tea intake and risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results. METHODS: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders. RESULTS: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94-0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47-0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30-0.71 for oral cavity; OR, 0.58; 95% CI, 0.41-0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37-1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64-1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89-1.11 for drinkers versus nondrinkers). CONCLUSIONS: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx. IMPACT: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance.

Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. METHODS: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). RESULTS: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). CONCLUSIONS: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy.MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 C, healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4cm.In conclusion, the data show that radiotherapy has a potent clastogenic effect in Circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm.

Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients

Purpose: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidentiologic variables.Experimental Design: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis.Results: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer.Conclusions: the significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.

Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

Objective: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors.Design: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n), repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG], repeats as an independent prognostic factor.Results: Patients with alleles <= 20 in the male group showed a correlation with lower disease-free survival (P = 0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). in the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n), repeat when compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures.Conclusion: These results suggest that short [CAG](n) repeat length (: 20) polymorphism is associated with poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors. (C) 2007 Elsevier Ltd. All rights reserved.

Markers of tumors susceptibility in head and neck cancer

Genetic polymorphisms are associated with a number of enzymes involved in the induction of head and neck carcinomas. It has been suggested that such polymorphisms may be linked to cancer susceptibility. Using a control-case study molecular genetic approach, we have investigated the association between polymorphisms genes (CYPs, GSTs and NAT2 genes) and susceptibility in head and neck cancer.

Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer

Hypermethylation in the promoter region has been associated with a loss of gene function that may give a selective advantage to neoplastic cells. In this study, the methylation pattern of genes CDKN2A (alias p14, p14(ARF), p16, p16(INK4a)), DAPK1, CDH1, and ADAM23 was analyzed in 43 samples of head and neck tumors using methylation-specific polymerase chain reaction. In the oropharynx, there was a statistically significant association between hypermethylation of the DAPK1 gene and the occurrence of lymph node metastases, and in the larynx there was statistically significant evidence of an association between hypermethylation of the ADAM23 gene and advanced stages of the tumors. Thus, a correlation was observed between hypermethylation of the promoter region of genes DAPK1 and ADAM23 and the progression of head and neck cancer. (c) 2007 Elsevier B.V. All rights reserved.