Disease burden, risk factors, and trends of lip, oral cavity, pharyngeal cancers: A global analysis.

BACKGROUND: Lip, oral and pharyngeal cancers make up a small percentage of total cancer cases worldwide and have reported lower rates of cancer-related deaths globally in 2020, but their 5-year survival rate in either early or advanced stages is different. The study evaluated the global incidence, mortality, risk factors, and temporal trends by age, gender, and geographical locations of lip, oral cavity, and pharyngeal cancer. METHODS: Incidence and mortality rates were extracted from Cancer Incidence in Five Continents (CI5) volumes I-XI, the Nordic Cancer Registries (NORDCAN), the Surveillance, Epidemiology, and End Results (SEER) Program, and the WHO IARC mortality database. Joinpoint regression was used to calculate the Average Annual Percentage Change to examine trends. RESULTS: The highest incidence rates were found in Melanesia and South-Central Asia and mortality rates were 8.2 and 7.5. Risk factors associated with incidence and mortality included HDI, tobacco use, alcohol consumption, poor diet, and chronic health conditions such as hypertension. Increasing trends of incidence and mortality were observed in females from Malta; males aged 50 and above from the United Kingdom, and females aged 50 and above from Slovakia reporting the largest increase. CONCLUSIONS: Although global incidence and mortality trends reported an overall decrease, significant increases were found for older age groups and female subjects. Incidence increase may be due to the growing prevalence of lifestyle, metabolic risk factors, and HPV infections, especially in developed countries.

Hyperfractionated intensity-modulated proton therapy for pharyngeal cancer with variable relative biological effectiveness: A simulation study.

BACKGROUND: The relative biological effectiveness (RBE) of proton is considered to be dependent on biological parameters and fractional dose. While hyperfractionated photon therapy was effective in the treatment of patients with head and neck cancers, its effect in intensity-modulated proton therapy (IMPT) under the variable RBE has not been investigated in detail. PURPOSE: To study the effect of variable RBE on hyperfractionated IMPT for the treatment of pharyngeal cancer. We investigated the biologically effective dose (BED) to determine the theoretical effective hyperfractionated schedule. METHODS: The treatment plans of three pharyngeal cancer patients were used to define the ΔBED for the clinical target volume (CTV) and soft tissue (acute and late reaction) as the difference between the BED for the altered schedule with variable RBE and conventional schedule with constant RBE. The ΔBED with several combinations of parameters (treatment days, number of fractions, and prescribed dose) was comprehensively calculated. Of the candidate schedules, the one that commonly gave a higher ΔBED for CTV was selected as the resultant schedule. The BED volume histogram was used to compare the influence of variable RBE and fractionation. RESULTS: In the conventional schedule, compared with the constant RBE, the variable RBE resulted in a mean 2.6 and 2.7 Gy reduction of BEDmean for the CTV and soft tissue (acute reaction) of the three plans, respectively. Moreover, the BEDmean for soft tissue (late reaction) increased by 7.4 Gy, indicating a potential risk of increased RBE. Comprehensive calculation of the ΔBED resulted in the hyperfractionated schedule of 80.52 Gy (RBE = 1.1)/66 fractions in 6.5 weeks. When variable RBE was used, compared with the conventional schedule, the hyperfractionated schedule increased the BEDmean for CTV by 7.6 Gy; however, this was associated with a 7.8 Gy increase for soft tissue (acute reaction). The BEDmean for soft tissue (late reaction) decreased by 2.4 Gy. CONCLUSION: The results indicated a potential effect of the variable RBE on IMPT for pharyngeal cancer but with the possibility that hyperfractionation could outweigh this effect. Although biological uncertainties require conservative use of the resultant schedule, hyperfractionation is expected to be an effective strategy in IMPT for pharyngeal cancer.

Incidence and survival in oral and pharyngeal cancers in Finland and Sweden through half century.

BACKGROUND: Cancers of the oral cavity and pharynx encompass a heterogeneous group of cancers for which known risk factors include smoking, alcohol consumption and human papilloma virus (HPV) infection but their influence is site-specific with HPV mainly influencing oropharyngeal cancer. Their incidence and survival rates are not well known over extended periods of time. PATIENTS/METHODS: Data were obtained for Finnish (FI) and Swedish (SE) patients from the Nordcan database recently updated through 2019. Age-adjusted incidence trends (FI from 1953, SE from 1960) and relative survival rates for years 1970 through 2019 were calculated. RESULTS: We observed a prominent increase in oral and oropharyngeal cancers in FI and SE men and women but the trend for oral cancer was interrupted for SE men in 1985 and possibly also for FI and SE women in 2015. The trend changes in male and female oral cancer was confirmed in data for Denmark and Norway. Relative survival for these cancers has improved overall but they differed for one cluster of oral, oropharyngeal and nasopharyngeal cancers with 60-70% 5-year survival in the last period and hypopharyngeal cancer with 25% male survival. In all these cancers, survival for old patients was unfavorable. DISCUSSION/CONCLUSION: We hypothesize that reduction in smoking prevalence helped to stop the increase in oral cancer especially in men. As the prevalence of smoking is decreasing, HPV is becoming a dominant risk factor, particularly for the increasing oropharyngeal cancer. Prevention needs to emphasize sexual hygiene and HPV vaccination.

Outcomes of Endoscopic Submucosal Dissection for Treatment of Superficial Pharyngeal Cancers: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Studies evaluating the role of endoscopic submucosal dissection (ESD) in the management of superficial pharyngeal cancers have reported promising results. This meta-analysis evaluates the efficacy and safety of ESD in the management of superficial pharyngeal cancers. METHODS: We reviewed several databases from inception to September 03, 2020, to identify studies evaluating the efficacy and safety of ESD in the management of superficial pharyngeal cancers. Our outcomes of interest were en bloc resection rate, complete resection rate, adverse events, and rates of local recurrence. Pooled rates with 95% confidence intervals (CI) for all outcomes were calculated using random-effect model. Heterogeneity was assessed by I2 statistic. We assessed publication bias by using funnel plots and Egger's test. We conducted meta-regression analysis to explore heterogeneity in analyses. RESULTS: Ten studies were included in analyses. All studies were from Asia. Pooled rates (95% CI) for en bloc resection and complete resection were 94% (87%, 97%) and 72% (62%, 80%), respectively. The pooled rates (95% CI) for adverse events and local recurrence were 10% (5%, 17%) and 1.9% (0.9%, 4%), respectively. Most of the analyses were limited by substantial heterogeneity. On meta-regression analysis, the heterogeneity was explained by size of tumor and histology. Funnel plots and Egger's test showed no evidence of publication bias. CONCLUSIONS: This meta-analysis including studies from Asian countries demonstrated that ESD is an efficacious and safe option in the management of superficial pharyngeal cancers. More studies and studies from Western countries are needed to further validate these findings.

Diet Quality as Measured by the Healthy Eating Index 2015 and Oral and Pharyngeal Cancer Risk.

BACKGROUND: Alcohol and tobacco are the major risk factors for oral and pharyngeal cancer, but diet is likely to have a role, too. OBJECTIVE: The objective was to analyze the relationship between adherence to the 2015-2020 Dietary Guidelines for Americans (DGA), as measured by the Healthy Eating Index 2015 (HEI-2015), and oral and pharyngeal cancer risk. Moreover, this work aimed to quantify the number of avoidable cases under different scenarios of increased adherence to the DGA, with the use of the potential impact fraction. This estimates the proportion of cases that would occur if the distribution of the risk factor in the population followed an alternative distribution. DESIGN: A multicenter, case-control study was conducted in Italy between 1991 and 2009. Participants' usual diet for the 2 years preceding study enrolment was assessed using a food frequency questionnaire. PARTICIPANTS AND SETTING: Cases were 946 patients admitted to major hospitals with incident, histologically confirmed oral and pharyngeal cancer. Controls were 2,492 patients admitted to the same hospitals for acute non neoplastic conditions. MAIN OUTCOME MEASURES: The adherence to the DGA was assessed using the HEI-2015 score (range = 0 to 100), based on 13 components. The outcome was oral and pharyngeal cancer. STATISTICAL ANALYSES PERFORMED: Odds ratios and the corresponding 95% CIs were estimated using multiple logistic regression models adjusted for tobacco, alcohol, and other relevant covariates. The potential impact fraction was estimated under different scenarios of adherence to the DGA. RESULTS: In this Italian population the HEI-2015 score ranged from 33.4 to 97.5. A higher HEI-2015 score was associated with a lower risk of oral and pharyngeal cancer, with an odds ratio of 0.70 (95% CI 0.62 to 0.79) for a 10-point increment of the score. The estimated potential impact fraction was 64.8% under the maximum achievable reduction scenario, and it ranged from 9% to 27% following other more feasible scenarios. CONCLUSIONS: The HEI-2015 score was inversely related to oral and pharyngeal cancer risk in this Italian population. This analysis allowed for the estimation of the fraction of preventable cases, under different feasible scenarios. A share of 9% to 27% of avoidable cases of oral and pharyngeal cancer might be obtained across real-world scenarios of adherence to the DGA as measured by the HEI-2015 score.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

Oral and pharyngeal cancer risk associated with occupational carcinogenic substances: Systematic review.

BACKGROUND: Oral and pharyngeal cancers (OPC) represent the seventh most common type of cancer and the seventh leading cause of deaths by cancer worldwide. Few studies have assessed the occupational exposure risks associated with OPC and in many cases the results are conflicting. The aim of this study was to determine, through a systematic review, the association of OPC and exposure to different occupational carcinogenic substances. METHODS: The addressed focused question was "Is there an association of occupational carcinogenic substances with OPC?" PubMed, MEDLINE, EMBASE, and ISI Web of Science databases were searched between January 1995 up to and including July 2016 using the keywords "oral cancer," "pharyngeal cancer," "pharyngeal neoplasms," "oral neoplasms," "occupational disease," "occupational exposure," and "occupational risk factor" in various combinations. Letters to the Editor, review articles, case reports, and unpublished articles were excluded. RESULTS: Fourteen original articles were included. Majority of the studies were conducted in European countries and used a case-control design. The results showed a significant association between formaldehyde, wood dust, coal dust, asbestos, welding fumes, and risk of developing OPC, while marginal association was observed with metal and leather dust. No associated risk was observed for textile fibers. CONCLUSION: There is some evidence to suggest associations of occupational substances with OPC, particularly in the pharynx. Future well-designed studies are required to confirm or rule out with confidence the associated exposure risk of these substances.

Managing head and neck malignancy arising in a field of Crohn disease inflammation: Report of a case.

Some of the clinical characteristics of Crohn disease of the head and neck overlap those of squamous cell carcinoma of the head and neck. We describe the diagnostic and therapeutic complexities we encountered in an unusual case of piriform sinus cancer that had arisen in a field of pharyngeal Crohn disease. Based on our initial failure to recognize the predominant inflammatory component of the lesion, we discuss the special considerations that must be made for the detection, staging, and management of head and neck cancer in Crohn disease patients. We further describe the multiple potential interactions among smoking, inflammation, and immunosuppression therapy in the colocalized pathogenesis of the two disease states.

Inflammatory potential of diet and risk of oral and pharyngeal cancer in a large case-control study from Italy.

Diet and inflammation have been suggested to be important risk factors for oral and pharyngeal cancer. We examined the association between dietary inflammatory index (DII™) and oral and pharyngeal cancer in a large case-control study conducted between 1992 and 2009 in Italy. This study included 946 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,492 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a valid 78-item food frequency questionnaire and was adjusted for nonalcohol energy intake using the residual approach (E-DII™). Logistic regression models were used to estimate odds ratios (ORs), and 95% confidence intervals (CIs), adjusted for age, sex, non-alcohol energy intake, study center, year of interview, education, body mass index, tobacco smoking, and alcohol drinking. Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of oral and pharyngeal cancer, the OR being 1.80 (95% CI 1.36-2.38) for the highest versus the lowest DII quartile and 1.17 (95% CI 1.10-1.25) for a one-unit increase (8% of the DII range). When stratified by selected covariates, a stronger association was observed among women (ORquartile4 v.1 3.30, 95% CI 1.95-5.57). We also observed a stronger association for oral cancers and a strong combined effect of higher DII score and tobacco smoking or alcohol consumption on oral and pharyngeal cancer. These results indicate that the pro-inflammatory potential of the diet, as shown by higher DII scores, is associated with higher odds of oral and pharyngeal cancer.

Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers.

Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD) but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO) gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future.

Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries.

BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control.

Awareness and Knowledge of Oral Cancer and Potentially Malignant Oral Disorders among Dental Patients in Far North Queensland, Australia.

BACKGROUND: Public awareness/knowledge on oral and pharyngeal cancer (OPC), potentially malignant disorders (PMODs) and their risk factors is crucial for prevention and early detection of OPC and PMODs. Yet, there are no published data available on the awareness and knowledge of OPC and PMODs among people living in Far North Queensland, Australia. MATERIALS AND METHODS: This study was conducted as a cross sectional survey. A self-administered questionnaire was designed and consisted of relevant questions to ascertain socio-demographic information, awareness and knowledge of OPC, PMODs and risk factors and questions on participant's exposure to risk factors and dietary history were also included. Survey was carried out at the Dental Clinic of the James Cook University School of Dentistry (JCU Dental), Cairns, Australia. Subjects above the age of 20 years (n=366) were randomly selected during the period from 31st July to 6th September 2013 and questionnaire was distributed to complete while they are waiting for treatment. Data analysis was carried out using SPSS version 21 and the chi -squared test was employed to compare groups. P<0.05 was considered statistically significant. RESULTS: The study revealed that 52.3% of the respondents were aware of the existence of OPC but only 19.0% were aware of PMODs. Of those who were aware of oral cancer, 92% agreed or strongly agreed that smoking is a strong risk factor for OPC. Similarly a relatively high proportion of the respondents agreed or strongly agreed that tobacco chewing (84%), tobacco chewing with areca nut (68%), chewing areca nut alone (51%) and exposure to actinic radiation (71%) as risk factors. However, the results for alcohol intake, age, and HPV infection were found to be relatively poor with proportions 33%, 34%, and 23% respectively. CONCLUSIONS: This study revealed an alarming lack of awareness and knowledge of OPC and PMODs.

Association study between novel CYP26 polymorphisms and the risk of betel quid-related malignant oral disorders.

BQ chewing may produce significant amounts of reactive oxygen species (ROS), resulting in oral mucosa damage, and ROS may be metabolized by CYP26 families. Because the CYP26 polymorphisms associated with malignant oral disorders are not well known, we conducted an association study on the associations between the single nucleotide polymorphisms (SNP) of CYP26 families and the risks of malignant oral disorders. BQ chewers with the CYP26A1 rs4411227 C/C+C/G genotype and C allele showed an increased risk of oral and pharyngeal cancer (adjusted odds ratio (aOR) = 2.30 and 1.93, respectively). The CYP26B1 rs3768647 G allele may be associated with oral and pharyngeal cancer (aOR = 3.12) and OPMDs (aOR = 2.23). Subjects with the rs9309462 CT genotype and C allele had an increased risk of oral and pharyngeal cancer (aOR = 9.24 and 8.86, respectively) and OPMDs (aOR = 8.17 and 7.87, respectively). The analysis of joint effects between the CYP26A1 rs4411227 and CYP26B1 rs3768647/rs9309462 polymorphisms revealed statistical significance (aOR = 29.91 and 10.03, respectively). Additionally, we observed a significant mRNA expression of CY26A1 and CYP26B1 in cancerous tissues compared with adjacent noncancerous tissues. Our findings suggest that novel CYP26 polymorphisms are associated with an increased risk of malignant oral disorders, particularly among BQ chewers.

An Ecological Analysis of Tobacco Use and Oral Cavity and Pharynx Cancers in U.S. Males.

BACKGROUND: As the 8th most frequently diagnosed cancers among U.S. males, cancers of the oral cavity and pharynx are a significant component of the cancer burden among U.S. males. Avoidance of tobacco products is critical for the prevention of oral cavity and pharynx cancers. The objective of this brief report was to describe state-specific incidence rates of oral cavity and pharynx cancers and to examine the correlation between state-specific prevalences of tobacco use and oral cavity and pharynx cancer incidence rates among U.S. adult males. METHODS: Secondary surveillance data were used to conduct this ecological analysis. Incidence rates of oral cavity and pharynx cancers during 2009 through 2011 among males were obtained from the Centers for Disease Control and Prevention (CDC) WONDER system. Prevalences of cigarette smoking and smokeless tobacco use during 1995 and 1996 among males were obtained from the CDC STATE System. Relations were examined by calculating Pearson correlation coefficients and by performing linear regression analysis. Statistical significance was considered at alpha < 0.05. RESULTS: Current cigarette smoking prevalence was significantly correlated (r = 0.57; r2 = 0.33; p-value = < .0001) with the incidence rate of oral cavity and pharynx cancer; while there was a non-statistically significant correlation (r = 0.22; r2 = 0.05; p-value = 0.1147) between smokeless tobacco use and oral cavity and pharynx cancer. A 1% increase in the prevalence of current cigarette smoking was estimated to increase the incidence rate of oral cavity and pharynx cancer by 0.52 per 100,000 males. Although non-statistically significant, a 1% increase in the prevalence of smokeless tobacco use was estimated to increase the incidence rate of oral cavity and pharynx cancer by 0.18 per 100,000 males. CONCLUSION: Among U.S. males, a statistically significant positive correlation was observed between cigarette smoking and oral cancer, but not between smokeless tobacco use and oral cancer. Moreover, current cigarette smoking was estimated to predict one-third of the total variability in oral cancer. These findings contribute to the body of literature and provide further evidence that cigarette smoking is an important behavioral risk factor for oral cavity and pharynx cancer among U.S. males.