Head And Neck Cancer Risk Research Articles

Passive smoking and risk of head and neck cancer: a systematic review and meta-analysis.

Studies on the association between passive smoking and head and neck cancer (HNC) are controversial. This meta-analysis aimed to explore this association. A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was conducted up to July 2024 to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model. Heterogeneity among studies was assessed, and the risk of bias was evaluated. A total of 1036 records were identified, of which 17 studies were included. Passive smoking was significantly associated with an increased risk of HNC overall (OR = 1.70, 95% CI: 1.27-2.28, P < 0.001). The association was particularly strong for oral cancer (OR = 1.85, 95% CI: 1.07-3.17, P = 0.026), oropharyngeal cancer (OR = 2.78, 95% CI: 1.29-5.98, P = 0.009), laryngeal cancer (OR = 1.60, 95% CI: 1.24-2.06, P < 0.001), and hypopharyngeal cancer (OR = 2.60, 95% CI: 1.45-4.66, P = 0.001). No significant association was observed for nasopharyngeal carcinoma (OR = 1.14, 95% CI: 0.78-1.66, P = 0.498). Geographically, the risk was elevated among both Asian and European populations. Passive smoking is associated with an increased risk of HNC, particularly for subtypes such as oral, oropharyngeal, laryngeal, and hypopharyngeal cancers. These findings underscore the importance of mitigating exposure to passive smoking as a public health measure.

Adherence to a low-fat dietary pattern reduces head and neck cancer risk: evidence from the PLCO trial

PurposeLow-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC).MethodsData were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results.ResultsAmong 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40–0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22–0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis.ConclusionOur findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population.

Body Mass Index, Height and Head and Neck Cancer Risk: the Japan Public Health Center-based Prospective Study.

Although both a lower and a higher body mass index (BMI) are reportedly associated with head and neck cancer (HNC), reports from Asia are scarce. Moreover, evidence regarding the association between height and HNC is limited. We investigated associations between BMI, height, and the incidence of HNC among 102,668 participants (49,029 men and 53,639 women) aged 40-69 years in the Japan Public Health Center-based Prospective Study. We followed participants from 1990 to 2013. We conducted a Cox proportional hazards regression analysis, which included adjustment for potential confounders such as smoking status. Baseline weight and height information were self-reported. Over an average follow-up of 18.7 years, 311 HNC cases were newly diagnosed. Lower BMI was significantly associated with HNC, with hazard ratios [HR] of 2.75 (95% confidence interval [CI]: 1.63-4.64) for <18.5 kg/m2 and 1.63 (95% CI=1.15-2.30) for 18.5-20.9 kg/m2 compared to 23-24.9 kg/m2. Increased risk was suggested for higher BMI, with an HR of 1.30 (95%CI=0.84-2.00) for ≥27.5 kg/m2. This trend was also observed in quadratic models. Results were similar among never smokers. Meanwhile, only lower BMI showed a strong association with HNC risk among former and current smokers (HR: 3.09, 95%CI: 1.54-6.20 for <18.5 kg/m2 compared to 23 to 24.9 kg/m2). Height showed no association with HNC. Lower BMI was significantly associated with HNC risk, while increased HNC risk was suggested in higher BMI among never smokers. Among former and current smokers, only lower BMI was associated with HNC risk.

Cannabis Use and Head and Neck Cancer

Cannabis is the most commonly used illicit substance worldwide. Whether cannabis use is associated with head and neck cancer (HNC) is unclear. To assess the clinical association between cannabis use and HNC. This large multicenter cohort study used clinical records from a database that included 20 years of data (through April 2024) from 64 health care organizations. A database was searched for medical records for US adults with and without cannabis-related disorder who had recorded outpatient hospital clinic visits and no prior history of HNC. Propensity score matching was performed for demographic characteristics, alcohol-related disorders, and tobacco use. Subsequently, relative risks (RRs) were calculated to explore risk of HNC, including HNC subsites. This analysis was repeated among those younger than 60 years and 60 years or older. Cannabis-related disorder. Diagnosis of HNC and any HNC subsite. The cannabis-related disorder cohort included 116 076 individuals (51 646 women [44.5%]) with a mean (SD) age of 46.4 (16.8) years. The non-cannabis-related disorder cohort included 3 985 286 individuals (2 173 684 women [54.5%]) with a mean (SD) age of 60.8 (20.6) years. The rate of new HNC diagnosis in all sites was higher in the cannabis-related disorder cohort. After matching (n = 115 865 per group), patients with cannabis-related disorder had a higher risk of any HNC (RR, 3.49; 95% CI, 2.78-4.39) than those without HNC. A site-specific analysis yielded that those with cannabis-related disorder had a higher risk of oral (RR, 2.51; 95% CI, 1.81-3.47), oropharyngeal (RR, 4.90; 95% CI, 2.99-8.02), and laryngeal (RR, 8.39; 95% CI, 4.72-14.90) cancer. Results were consistent when stratifying by older and younger age group. This cohort study highlights an association between cannabis-related disorder and the development of HNC in adult patients. Given the limitations of the database, future research should examine the mechanism of this association and analyze dose response with strong controls to further support evidence of cannabis use as a risk factor for HNCs.

The role of herpes simplex virus infection in the etiology of head and neck cancer-a Mendelian randomization study.

Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear. This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR-Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses. Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy. Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.

Genetic predisposition to milder forms of COVID-19 may provide some resilience to head and neck cancers.

The impact of the COVID-19 pandemic on head and neck cancer (HNC) has been suggested, but the causal relationship remains unclear. We explore this connection by utilizing the Mendelian randomization (MR) approach applied to publicly available genome-wide association study (GWAS) summary datasets for COVID-19 and HNC. The datasets included critical COVID-19 (13,769 cases, 1,072,442 controls), hospitalized COVID-19 (32,519 cases, 2,062,805 controls), SARS-CoV-2 infection (122,616 cases, 2,475,240 controls), and HNC (2,131 cases, 287,137 controls). Mechanistic underpinnings of the causal relationships identified by MR analysis were explored through functional annotation augmented by AI-based literature data mining. Surprisingly, a genetic predisposition to contracting a milder form of COVID-19 substantially reduced the risks of developing HNC (OR: 0.52, 95% CI: 0.35-0.78, p = 1.42E-03), with no significant association between genetic liability to severe COVID-19 and the risk of HNC detected. Additionally, our findings highlighted 14 genes linked to SARS-CoV-2 infection, potentially playing a protective role in the context of HNC. These genes include OAS1, LOC107985887, BCL11A, DPP9, LOC107984685, LINC02326, MUC4, NXPE3, IFNAR2, LZTFL1, LOC105372437, NAPSA, LOC105376622, LOC107986082, and SLC6A20. Our study emphasizes the protective role of the genetic liability to milder COVID-19 in reducing the risk of HNC while refuting a causal relationship between severe COVID-19 and HNC.

Allergies and risk of head and neck cancer: a case–control study

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case–control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58–88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Nomenclature of the symptoms of head and neck cancer: a systematic scoping review.

Evolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients' clinical problems more effectively and risk stratify the patient. The review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms. There were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings. Symptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician's decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.

Development and external validation of a head and neck cancer risk prediction model.

Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection. The IARC-ARCAGE European case-control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics. 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74-0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61-0.64). We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction.

Association of Gout with Head and Neck Cancer: Longitudinal Follow-Up Studies Using a National Health Insurance Database in South Korea.

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04-1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16-1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01-1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06-1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72-0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83-0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81-0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC.

Abstract 1001: Association between oral cancer screening and knowledge of head and neck cancer symptoms and risk factors among Arab Americans

Abstract Background: Head and neck cancer (HNC) has been increasingly affecting individuals of different ages, significantly contributing to the annual cancer burden in the US. While most HNC cases present at late-stages and are more likely to require aggressive surgical interventions with higher mortality, those who present with premalignant clinical signs or early-stages have a 5-year survival of 70%-90%. Moreover, current HNC public awareness is poor with lack of data on cultural and ethnic minorities. This study evaluated the association between oral cancer screening (OCS) recommendation and receipt and HNC symptoms and risk factors knowledge among Arab Americans in Michigan. Methods: This was a cross-sectional study of adult Arab Americans conducted between March and July 2023. Surveys were available in English and Arabic per participants preference. Outcome variables were knowledge of three main HNC risk factors—alcohol, cigarette smoking, and HPV— and four of the most common HNC symptoms—nonhealing oral ulcers, dysphagia/odynophagia, voice changes and neck/throat masses—defined as yes/no. OCS was captured as receiving provider-given recommendation for screening and undergoing a screening test (yes/no). Multivariable logistic regression models estimated the associations between OCS and HNC symptoms and risk factor knowledge adjusting for socioeconomic factors. Results: A total of 295 respondents were included in the study, 9% had received recommendation for OCS and 11% had undergone a screening test. In adjusted models, respondents who did not correctly identify nonhealing oral ulcers (aOR=0.20; 95% CI 0.06-0.67) as HNC symptoms or HPV (aOR=0.15; 95% CI 0.04-0.55) as risk factor of HNC were less likely to have received provider-given recommendation for OCS compared to those who identified the symptom and risk factor. Similarly, respondents who did not correctly identify nonhealing oral ulcers (aOR=0.13; 95% CI 0.04-0.42), dysphagia or odynophagia (aOR=0.22; 95% CI 0.07-0.70), voice changes (aOR=0.27; 95% CI 0.09-0.81), and neck/throat masses (aOR=0.24; 95% CI 0.06-0.91) as HNC symptoms or HPV (aOR=0.07; 95% CI 0.02-0.29) and alcohol (aOR=0.17; 95% CI 0.05-0.58) as HNC risk factors were less likely to have undergone OCS compared to those who identified the symptoms and risk factors. Conclusion: Respondents who reported limited knowledge of HNC symptoms and risk factors were less likely to be exposed to screening recommendations or testing. Combining screening with education on premalignant and early-stage clinical signs and risk factors might facilitate reduction of HNC incidence and late diagnosis. Further interventions are needed to increase Arab Americans education and identification of high-risk groups by their providers. As HNC screening efficacy remains controversial, future efforts should be directed towards deepening our understanding in this area. Citation Format: Nada Al-Antary, Reem Siddiqui, Marissa Gilbert, Lamis Fakhoury, Mrudula Nair, Farzan Siddiqui, Eric Adjei Boakye. Association between oral cancer screening and knowledge of head and neck cancer symptoms and risk factors among Arab Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1001.

Abstract 2222: Knowledge of risk factors and symptoms of head and neck cancers among Arab-Americans

Abstract Background: In 2023, approximately 66000 patients with head and neck cancers (HNC) will be diagnosed in the United States (U.S.). There are approximately 3.7 million Arab-Americans living in the U.S., with large concentration in Michigan (MI). For example, Dearborn, MI has the largest percentage of Arab-Americans (40% of people having Arab ancestry). Smoking, alcohol, and human papillomavirus (HPV) are the main causes of HNC. Common symptoms of HNC are lump in the neck/mouth, nonhealing ulcers, dysphagia or odynophagia, and change in voice. Currently, there is a scarcity of research on knowledge of HNC risk factors and symptoms among Arab-Americans. We examined knowledge of risk factors and symptoms of HNC among Arab-Americans residing in MI. Methods: This was a cross-sectional study of adult Arab-Americans (≥18 years) conducted between March and July 2023. Survey questions were adapted from the National Cancer Institute and Centers for Disease Control and Prevention and offered in English and Arabic depending on respondent preference. Awareness of the symptoms of HNCs were assessed using 14 questions while risk factors were assessed using 10 questions. The questions were in the form of “Do you know that the following can be symptoms/risk factors of HNC?” Respondents selected “yes,” “no,” or “don’t know/not sure” for each answer choice. Results: Of the 295 Arab-Americans survey respondents, the mean age ± SD was 37.9 ± 14.6, and most were female (60.7%), had at least a college degree (57.6%), private health insurance (56.7%), and usual place of receiving care (70.7%). Majority had no history of cigarette use (81.7%) or alcohol use (91.6%). Regarding HNC symptoms knowledge, only 40-50% knew about most common HNC symptoms: nonhealing ulcers (41%), dysphagia or odynophagia (51.4%), and voice changes (48.6%); while 60.6% knew about swelling or lump in neck/throat. About half of respondents knew of persistent mass or lesion on the tongue (53.3%) and bleeding in the mouth or throat (50.3%) as symptoms of HNC. About a third knew these as HNC symptoms: teeth loosening (31.7%), ill-fitting dentures (25.9%), otalgia (37.8%), and nasal obstruction/congestion (34.9%). For HNC risk factors knowledge, tobacco smoking, chewing, and second-hand smoking were the most common recognized risk factors, identified by 78.9%, 72.8% and 66.8%, respectively. However, less than half knew HPV (40.6%) and Epstein-Barr virus (35.4%) as risk factors. Conclusion: While there is higher knowledge about tobacco as a risk factor for HNC, knowledge about HPV as a risk factor is very low. Similarly, knowledge about HNC symptoms is suboptimal in the Arab-American community, which could result in late-stage presentation and thus lower survival. Educational programs designed for this community are needed to help close this gap and improve HNC related health outcomes among culturally and ethnically distinct Arab-Americans. Citation Format: Eric Adjei Boakye, Reem F. Siddiqui, Nada Al-Antary, Marissa Gilbert, Lamis Fakhoury, Milkie Vu, Farzan Siddiqui. Knowledge of risk factors and symptoms of head and neck cancers among Arab-Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2222.

Smoking, Drinking, and Dietary Risk Factors for Head and Neck Cancer in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Participants

There is a paucity of large-scale prospective studies evaluating the risk of developing head and neck cancer (HNC) associated with smoking, drinking, and dietary habits. To determine the association of smoking, drinking, and dietary habits with the risk of developing HNC. A nested cohort survival analysis of Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants was performed. Participants were between 55 and 74 years of age and recruited at 10 centers across the US from November 1993 to July 2001. Participants who developed HNC were matched with controls based on demographics and family history of HNC for analysis of smoking habits; for the analysis of drinking and dietary habits, matching was performed on smoking status and duration in addition to demographics and family history of HNC. Data analysis was performed from January to November 2023. Smoking, drinking, and dietary habits. Diagnosis of HNC. In total, 139 926 participants (51% female; mean [SD] age, 62.6 [5.4] years) were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.1 (10.3-13.6) years, 571 of whom developed HNC. HNC risk associated with smoking increased the closer the proximity of the head and neck subsite to the lungs, with the greatest risk associated with smoking observed in laryngeal cancer (current smoker hazard ratio [HR], 9.36; 95% CI, 5.78-15.15 compared to a nonsmoker). For analysis of drinking and dietary habits, 94 466 participants were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.2 (10.5-13.6) years, 264 of whom developed HNC. HNC risk increased with heavy drinking (HR, 1.85; 95% CI, 1.44-2.38) and decreased with consumption of whole grains (HR, 0.78; 95% CI, 0.64-0.94/oz per day), whole fruits (HR, 0.90; 95% CI, 0.82-0.98/cup per day), and overall healthy eating, as scored by Healthy Eating Index 2015 (HR, 0.87; 95% CI, 0.78-0.98/10 points). In this nested cohort study, the risk of HNC associated with smoking was higher for subsites that were closer to the lungs; heavy drinking was associated with greater HNC risk, while healthy eating was associated with a modest reduction in HNC risk.

Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Aspirin intake and head and neck cancer: A pooled analysis within the INHANCE consortium.

Aspirin intake might be inversely associated with head and neck cancer (HNC). Thus, we investigated this relationship within the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Four case-control studies within the INHANCE consortium were included (2024 cases, 4196 controls). Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression and subsequently pooled with DerSimonian-Laird random-effects model. Nonlinearity of the relationship between duration of intake and HNC was modeled with fractional polynomials. Aspirin was inversely associated with HNC overall (OR = 0.48; 95% CI: 0.26, 0.91). Results for laryngeal cancer were similar (OR = 0.54; 95% CI: 0.30, 0.96). Analysis on duration of intake confirmed findings for HNC overall, showing also inverse associations for oropharyngeal and laryngeal cancer. This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer.

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy.

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

Association of the cytochrome P450 and arylamine N-acetyltransferase gene polymorphisms with the incidence of head and neck cancer in Polish population.

Head and neck cancer (HNC) is one of the most common cancers. Most exogenous HNC is head and neck squamous cell carcinomas. Scientists are striving to develop diagnostic tests that will allow the prognosis of HNC. The aim of the study was to determine the risk of HNC. The research concerned changes caused by polymorphisms in genes encoding proteins responsible for the metabolism of xenobiotics. In group of 280 patients with HNC, the occurrence of polymorphic variants in NAT1(rs72554606), NAT2(rs1799930), CYP1A(rs1799814), CYP2D(rs3892097) were studied with TaqMan technique. The control group consisted of 260 cancer free people. The TNM scale was analyzed. Gene interactions of genotyped polymorphisms were investigated. The effects of smoking and alcohol consumption on HNC were assessed. The results indicated an increased risk of HNC in NAT1 polymorphisms in the GC genotype (OR = 1.772, 95% CI: 1.184-2.651, p = 0.005) and NAT2 polymorphism in the GA genotype (OR = 1.506, 95% CI: 1.023-2.216, p = 0.037). The protective phenomenon in the CYP1A polymorphism the GT genotype (OR = 0.587, 95% CI: 0.381-0.903, p = 0.015) and the TT genotype (OR = 0.268, 95% CI: 0.159-0.452, p = 0.001). The coexistence of GA-GC polymorphisms (OR = 2.687, 95% CI: 1.387-5.205, p = 0.003) in NAT2-NAT1 genes increases the risk of HNC. Risk-reducing effect in the polymorphism GG-GT (OR = 0.340, 95% CI: 0.149-0.800, p = 0.011), GG-TT (OR = 0.077, 95% CI: 0.028-0.215, p < 0.0001), GA-TT (OR = 0.250, 95% CI: 0.100-0.622, p = 0.002), AA-GT (OR = 0.276, 95% CI: 0.112-0.676, p = 0.002) in NAT2-CYP1A genes. In the CYP2D-CYP1A genes in the polymorphisms CT-CC (OR = 0.338, 95% CI: 0.132-0.870, p = 0.020), TT-GG (OR = 0.100, 95% CI: 0.027-0.359, p = 0.001), TT-GC (OR = 0.190, 95% CI: 0.072-0.502, p = 0.0004), TT-CC (OR = 0.305, 95% CI: 0.107-0.868, p = 0.024). Correlation was noted between cigarette smoking and HNC (OR = 7.297, 95% CI: 4.989-10.674, p < 0.0001) and consuming alcohol (OR = 1.572, 95% CI: 1.003-2.464, p = 0.047). The CYP1A polymorphism shows a protective association with HNC. On the other hand, NAT2, NAT1 polymorphism influence the susceptibility to developing HNC. The coexistence of the NAT2-NAT1 genotypes increases the risk of HNC. In contrast, NAT1-CYP1A and CYP1A-CYP2D reduce this risk. Smoking and alcohol consumption increase the incidence of HNC. Int J Occup Med Environ Health. 2023;36(6):812-24.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

PurposeTo investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.MethodsOur study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome.ResultsDuring a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14–1.34) and OAC (HR = 1.24, 95% CI 1.05–1.47). WHR mediated 5% (95% CI 3–10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6–53%) and 15% (95% CI 8–72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis.ConclusionsWe reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Risk of head and neck cancer in relation to blood inflammatory biomarkers in the Swedish AMORIS cohort.

Inflammation is critically involved in the development of human cancer, and blood inflammatory biomarkers have been proposed to indicate the risk of different cancer types. Using the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) Cohort (N=812,073), we first performed a time-to-event analysis to evaluate the association of the baseline level of 12 blood inflammatory biomarkers measured during 1985-1996 with the subsequent risk of head and neck cancer (HNC) identified through the nationwide Swedish Cancer Register until end of 2020. A nested case-control study was further conducted to demonstrate the longitudinal trends of the studied biomarkers during the 30-year period prior to diagnosis of HNC. In the time-to-event analysis, we identified a total of 2,510 newly diagnosed HNC cases. There was an increased risk of HNC per standard deviation (SD) increase of haptoglobin (hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.21-1.30), leukocytes (HR: 1.22; 95%CI: 1.17-1.28), sedimentation rate (HR: 1.17; 95%CI: 1.07-1.29), and monocytes (HR: 1.34; 95%CI: 1.07-1.68) at baseline, after adjustment for age, sex, fasting status, occupational status, and country of birth. In contrast, there was a decreased risk of HNC per SD increase of lymphocytes in % (HR: 0.85; 95%CI: 0.73-0.99) and lymphocyte-to-monocyte ratio (LMR) (HR: 0.81; 95%CI: 0.69-0.95) at baseline. In the nested case-control study using repeatedly measured biomarker levels, we found that individuals with HNC had consistently higher levels of haptoglobin, leukocytes, sedimentation rate, and monocytes, as well as consistently lower levels of lymphocytes in % and LMR, during the 30-year period prior to diagnosis, compared to controls. Based on a cohort of more than half a million participants with up to 35 years of follow-up, our findings provide solid evidence supporting the presence of alterations in blood inflammatory biomarkers during the decades before diagnosis of HNC.

Dietary total antioxidant capacity and head and neck cancer: a large case-control study in Iran.

Data on the association between head and neck cancer (HNC) and dietary factors are inconclusive. No study has so far investigated the association between dietary total antioxidant capacity (dTAC) and HNC concerning interactions with other risk factors. Pathologically confirmed new diagnosed HNC patients were included in this study. The control group was healthy hospital visitors who were frequently matched with patients on age (5 years interval), gender, and province of residence. Trained interviewers administered a validated Food Frequency Questionnaire (FFQ) to assess the participants' food intake 1 year before the cancer diagnosis. Data on TAC scores of foods was collected by Ferric Reducing Antioxidant Power (FRAP) and Total Radical-trapping Antioxidant Parameters (TRAP) from published data. We applied logistic regression adjusted for age, sex, energy intake, socioeconomic status, province, opium use, alcohol use, physical activity, and dental health. We also studied the interaction of dTAC with tobacco smoking status, and opium use on the risk of HNC. We recruited 876 HNC patients and 3,409 healthy controls. We observed a significant decrease in the odds of HNC with increasing dTAC scores. The OR of HNC for the third vs. the first tertile was 0.49 (95%CI 0.39-0.61) for FRAP and 0.49 (95%CI 0.39-0.62) for TRAP. Both dTAC scores were inversely associated with lip and oral (T3 ver. T1 OR = 0.51; 95%CI 0.36-0.71 for FRAP and OR = 0.59; 95% CI 0.44-0.82 for TRAP) and larynx (T3 ver. T1 OR = 0.43; 95%CI 0.31-0.61 for FRAP and OR = 0.38; 95% CI 0.26-0.55 for TRAP) cancers. There was no interaction between tobacco smoking, opium use; and TRAP or FRAP on the risk of HNC. An antioxidant-rich diet in terms of FRAP or TRAP could decrease the risk of HNC and its subtypes.