Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

A clinicopathological study of upper aerodigestive tract cancers.

BACKGROUND: The upper aerodigestive tract (UAT) includes the nose and paranasal sinuses, oral cavity, pharynx, larynx, and salivary glands. Cancers of the UAT constitute approximately 4% of all malignancies. In this study, the varied nature of the UAT cancers was studied to find out their incidence, etiology, and clinicopathological correlations. MATERIALS AND METHODS: This prospective, observational, and clinicopathological study was conducted on 100 patients who were presented at outdoor in the Department of ENT, Government Medical College/Rajindra Hospital, Patiala, Punjab, India, from October 2016 to October 2018. Proven cases of UAT cancers were taken up and reviewed to gather data on multiple clinicopathological variables, such as age, sex, predisposing factors, and site of pathology. Histopathological differentiation was noted after conducting a biopsy. RESULTS: Most patients of UAT cancers were in the age group of 40-70 years. Maximum incidence was among males (82%) compared to females (28%). The most common predisposing factor was alcohol + smoking (28%), followed by alcohol + chewing tobacco (25%). The most common symptom in the oral cavity was ulcer and odynophagia (38%) each. In oropharyngeal cancers, dysphagia (92%) was the most common symptom. In laryngeal cancers, dyspnea (68%) and hoarseness of voice (32%) were the most common. The most common site involved in UAT cancers was the oral cavity (31%), followed by oropharynx (28%), larynx (22%), hypopharynx (7%), and salivary gland (5%). The most common histopathological type was squamous cell carcinoma (SCC) (90%). Most of the ulceroproliferative and exophytic growth was moderately differentiated SCC on histopathology. CONCLUSION: Studies are essential for education and awareness aimed at reducing exposure to habit-forming substances.

A risk factor-based model for upper aerodigestive tract cancers in India: predicting and validating the receiver operating characteristic curve.

BACKGROUND: A study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing upper aerodigestive tract (UADT) cancers in an Indian population. METHODS: A hospital-based case-control study (n = 480) was conducted in Pune, India. We assessed risk factors for UADT cancers by administering a questionnaire through face-to-face interviews. We developed a risk factor model based on the statistically significant risk factors in multiple logistic regression. A total, single risk score was calculated per individual based on the adjusted odds ratio for each of their risk factors. Standard receiver operator characteristic curve was plotted for the total score and the presence of UADT cancers. The stratification ability of the model was determined using the c-statistic. The optimal criterion value was determined at the point on curve at which the Youden's index was maximal. Confidence intervals were calculated by bootstrapping. RESULTS: Total risk score for each individual ranged from 0 to 26. Area under the receiver operating characteristic curve (95.8; P < 0.001) suggests strong predictive ability. A risk score criterion value of ≤10 produced optimal sensitivity (93.5%), specificity (71.1%), false-positive rate (28.8%), false-negative rate (6.4%), positive predictive value (74.8%), and negative predictive value (96.6%). CONCLUSION: This risk factor-based model has the potential of satisfactorily screening and detection of UADT cancers at its early stage in a high-risk population like India. The identified at-risk individuals can then be targeted for clinical examination and for focused preventive/treatment measures at the hospital.

Epigenetic pathogenesis of human papillomavirus in upper aerodigestive tract cancers.

Human papillomavirus (HPV) has been recently associated with squamous cell carcinoma of upper aerodigestive tract (SCC of UADT), but its possible role in promoting aberrant methylation in these tumors has largely remained unexplored. Herein, we investigated the association of HPV with aberrant methylation in tumor-related genes/loci consisting of the classical CpG Island Methylator Phenotype (CIMP) panel markers (p16, MLH1, MINT1, MINT2, and MINT31) and other frequently methylated cancer-related genes (DAPK1, GSTP1, BRCA1, ECAD, and RASSF1) and survival of UDAT cancers. The study includes 219 SCC of UADT patients from different hospitals of Northeast India. Detection of HPV and aberrant promoter methylation was performed by PCR and Methylation Specific PCR respectively. Association study was conducted by Logistic regression analysis and overall survival analysis was done by Kaplan-Meier plot. HPV was detected in 37% of cases, with HPV-18 as the major high-risk sub-type. Although HPV presence did not seem to affect survival in overall UADT cancers, but was associated with a favourable prognosis in head and neck squamous cell carcinoma. Hierarchical clustering revealed three distinct clusters with different methylation profile and HPV presence. Among these, the CIMP-high subgroup exhibited the highest HPV positive cases (66%). Furthermore, multivariate analysis revealed a strong synergistic association of HPV and tobacco towards modulating promoter hypermethylation in UADT cancer (OR = 27.50 [95% CI = 11.51-88.03] for CIMP-high vs. CIMP-low). The present study proposes a potential role of HPV in impelling aberrant methylation in specific tumor related loci, which might contribute in the initiation and progression of SCC of UADT.

Association between dietary inflammatory index and upper aerodigestive tract cancer risk: A systematic review and dose-response meta-analysis.

OBJECTIVES: The relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk have been investigated in a growing number of epidemiological studies. However, their findings were inconsistent, and no systematic review or meta-analysis has been conducted up to now. This meta-analysis was carried out to examine potential dose-response relationship between DII score and UADT cancer risk. MATERIAL AND METHODS: A systematic search was conducted for relevant studies in PubMed and Web of Science up to March 28, 2019. Categorical meta-analysis as well as linear and non-linear dose-response meta-analysis were performed to evaluate association between DII and UADT cancer risk. RESULTS: Nine case-control studies with a total of 4138 cases and 15,326 healthy controls were eligible in the present meta-analysis. The pooled odds ratios (ORs) of UADT cancer risk were 2.07 [95% confidence interval (CI): 1.82, 2.35] for the highest DII score compared with the lowest and 1.53 (95% CI: 1.39, 1.69) for higher DII score compared with lower score, respectively. Furthermore, a one-unit increment in DII score was associated with an increased risk of 18% for UADT cancers (OR: 1.18; 95% CI: 1.15, 1.21). An upward trend towards a positive association between elevated DII score and UADT cancer risk was also observed in non-linear dose-response meta-analysis. CONCLUSIONS: The present meta-analysis provides evidence of highly pro-inflammatory diets that might increase risk of UADT cancers. Therefore, reducing pro-inflammatory components in diets should be considered to prevent and control UADT cancers.

Smokeless Tobacco Use, Cigarette Smoking, and Upper Aerodigestive Tract Cancers: A Case-Control Study in the Batna Region, Algeria, 2008-2011.

BACKGROUND: A significant proportion of the Algerian population uses tobacco products and is at risk of developing tobacco-associated cancers. AIMS: This case-control study reports on the association between tobacco use and the occurrence of upper aerodigestive tract (UADT) cancers in Batna, Algeria. METHODS: Incident primary UADT cancer cases in residents of Batna in 2008-2011 were identified using the regional tumor registry. One hospital and 1 population control were matched to each case by sex, year of birth, and residence. Information on tobacco use was collected, and odds ratios (ORs) were obtained using conditional logistic regression also after sex stratification. RESULTS: The study included 192 cases (80%) of the 241 primary UADT cancer cases identified and 384 controls. Males represented 76.6% of cancer cases. Cancers of the nasopharynx (48%) and the larynx (26%) were the most common types. Ever use of smokeless tobacco (ST) (OR = 1.0; 95% confidence interval [CI]: 0.6-1.5) or current ST use (OR = 1.1; 95% CI: 0.6-1.7) was not associated with overall risk of UADT cancers. Associations with cancers of the nasopharynx (OR = 1.5; 95% CI: 0.5-4.6) and oral cavity/oropharynx (OR = 3.0; 95% CI: 0.8-11.8) were found when comparing use of ST only to no consumption of any tobacco. Cigarette smoking was associated with an increase in the overall risk of UADT cancers, with a 3-fold increase in the risk of laryngeal cancer when comparing smoking only to no consumption of any tobacco (OR = 3.3; 95% CI: 1.0-11.5). Associations for smokers who also consumed ST differed by cancer site. CONCLUSION: In this study from Algeria dominated by male cases and by cancer in the nasopharynx, cigarette smoking but not ST was associated with UADT cancer. Analyses by anatomical site and using as reference never use of any type of tobacco suggested few associations with ST but of lower precision.

Metastatic Squamous Cell Carcinoma to the Cervical Lymph Nodes From an Unknown Primary Cancer: Management in the HPV Era.

BACKGROUND: Patients with metastases in the lymph nodes of the neck and no obvious primary tumor, neck cancer with unknown primary (NCUP), represent a management challenge. A majority of patients have metastatic squamous cell carcinoma (SCC), although other histologies do occur. METHODS: We comprehensively reviewed the literature, compared available guidelines, and conferred with an international team of experts. RESULTS: Positron emission tomography-computed tomography (PET-CT) and fine needle aspiration (FNA) under ultrasound guidance increase accuracy of diagnosis. Immunohistochemistry (IHC), determination of human papilloma virus (HPV) status, by p16 staining or by in situ hybridization (ISH), and next-generation gene sequencing can guide us regarding probable primary sites and tumor biology. Narrow Band Imaging (NBI) has been introduced for the early detection of subtle mucosal lesions. Direct laryngoscopy (DL) and tonsillectomy have long been procedures used in the search for a primary site. More recently, TransOral Robotic Surgery (TORS) or Transoral LASER Microsurgery (TLM) have been introduced for lingual tonsillectomy. CONCLUSIONS: New technologies have been developed which can better detect, diagnose, and treat occult primary tumors. Decisions regarding therapy are based on the primary tumor site (if discovered) and N stage. Options include neck dissection with or without postoperative adjuvant therapy, primary irradiation, or combined chemotherapy with irradiation. The preferred treatment of patients whose primary remains unidentified is controversial.

Evidence of past dental visits and incidence of head and neck cancers: a systematic review and meta-analysis.

BACKGROUND: Regular/frequent dental visits, at least annually, can aid in reducing the public health burden of head and neck cancers (HNCs) by facilitating earlier detection of the disease. The aim of this study was to conduct a quantitative assessment of any independent association between past dental visits/check-ups and incidence of cancers of HN/upper aerodigestive tract (UADT) and oral cavity worldwide. METHODS: PubMed, CINAHL, and Cochrane databases were searched for all observational studies published until August 2017 in any language that assessed an association of past dental visits/dental check-ups among the incident cases of HNC/UADT cancers. Screening and quality assessment of the articles was performed by two independent reviewers. Three different meta-analyses were conducted: two based on the incident cancer reported in the studies (HNCs/cancers of UADT and oral cavity); another included all studies irrespective of the type of cancer reported with the frequency of past dental visits as subgroups. RESULTS: Searches retrieved 3164 titles: after removing duplicates, 1377 remained. Of these, 62 were reviewed in full, but only 38 were eligible for inclusion. Under the random effects model, odds of past never/irregular/not frequent dental visits were greater in HNC cases and oral cancer cases as compared to the hospital-based/population-based controls [HNCs-unadjusted odds ratio (OR) 2.24; 95% confidence interval (CI) 1.89 to 2.65) and (oral cancers-OR 1.93; 95% CI 1.47 to 2.52]. Similar results were observed for all cancers with frequency of past dental visits as subgroup analysis (OR 2.01; 95% CI 1.76 to 2.30). Meta-regression findings indicate that none of the subgroup influenced the effect estimates for incidence of cancers. There was no publication bias in our study. CONCLUSION: This systematic review and meta-analysis indicates that individuals with never/irregular/not frequent dental visits are more likely to be incident cases of HNCs/UADT cancers.

Maté consumption association with upper aerodigestive tract cancers: A systematic review and meta-analysis.

Maté is a beverage regularly consumed by Latin American populations. Upper aerodigestive tract (UADT) cancers are frequent in this region and are suspected to be associated with maté consumption. The aim of this systematic review and meta-analysis was to answer a focused question: "Is there an association between maté consumption and occurrence of the UADT cancer?". Studies investigating any association between maté consumption and occurrence of UADT cancer were included. Out of the 569 studies, 18 met the inclusion criteria for qualitative and 15 for quantitative analysis. An increased odds was observed regarding maté consumption and overall occurrence of UADT cancer (OR = 2.24; 95%CI = 1.74-2.87). Consistent evidence of a positive association was found for all UADT subsites, oral, pharynx, esophagus and larynx. No differences in effect were found between consumption of cold/warm and hot/very hot mate (OR = 1.08; 95%CI = 0.83-1.41). Consumption of more than one liter of maté per day was associated with increased odds of having UADT cancer compared to an intake of less than one liter per day (OR = 1.72; 95%CI = 1.47-2.01). According to published data, regardless of the temperature, maté consumption significantly increased the odds of occurrence of UADT cancer.

Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers.

Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.