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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer.

Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.

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

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

Dietary glycaemic index, glycaemic load and head and neck cancer risk: a pooled analysis in an international consortium.

High dietary glycaemic index (GI) and glycaemic load (GL) may increase cancer risk. However, limited information was available on GI and/or GL and head and neck cancer (HNC) risk. We conducted a pooled analysis on 8 case-control studies (4081 HNC cases; 7407 controls) from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of HNC, and its subsites, from fixed- or mixed-effects logistic models including centre-specific quartiles of GI or GL. GI, but not GL, had a weak positive association with HNC (ORQ4 vs. Q1 = 1.16; 95% CI = 1.02-1.31). In subsites, we found a positive association between GI and laryngeal cancer (ORQ4 vs. Q1 = 1.60; 95% CI = 1.30-1.96) and an inverse association between GL and oropharyngeal cancer (ORQ4 vs. Q1 = 0.78; 95% CI = 0.63-0.97). This pooled analysis indicates a modest positive association between GI and HNC, mainly driven by laryngeal cancer.

Risk Prediction Models for Head and Neck Cancer in the US Population From the INHANCE Consortium.

Head and neck cancer (HNC) risk prediction models based on risk factor profiles have not yet been developed. We took advantage of the large database of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, including 14 US studies from 1981-2010, to develop HNC risk prediction models. Seventy percent of the data were used to develop the risk prediction models; the remaining 30% were used to validate the models. We used competing-risk models to calculate absolute risks. The predictors included age, sex, education, race/ethnicity, alcohol drinking intensity, cigarette smoking duration and intensity, and/or family history of HNC. The 20-year absolute risk of HNC was 7.61% for a 60-year-old woman who smoked more than 20 cigarettes per day for over 20 years, consumed 3 or more alcoholic drinks per day, was a high school graduate, had a family history of HNC, and was non-Hispanic white. The 20-year risk for men with a similar profile was 6.85%. The absolute risks of oropharyngeal and hypopharyngeal cancers were generally lower than those of oral cavity and laryngeal cancers. Statistics for the area under the receiver operating characteristic curve (AUC) were 0.70 or higher, except for oropharyngeal cancer in men. This HNC risk prediction model may be useful in promoting healthier behaviors such as smoking cessation or in aiding persons with a family history of HNC to evaluate their risks.

Tobacco smoking, chewing habits, alcohol drinking and the risk of head and neck cancer in Nepal.

Although tobacco smoking, pan chewing and alcohol drinking are important risk factors for head and neck cancer (HNC), the HNC risks conferred by products available in Nepal for these habits are unknown. We assessed the associations of tobacco smoking, chewing habits, and alcohol drinking with HNC risk in Nepal. A case-control study was conducted in Nepal with 549 incident HNC cases and 601 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. We observed increased HNC risk for tobacco smoking (OR: 1.54; 95% CI: 1.14, 2.06), chewing habits (OR: 2.39; 95% CI: 1.77, 3.23), and alcohol drinking (OR: 1.57; 95% CI: 1.14, 2.18). The population attributable fraction (PAF) was 24.3% for tobacco smoking, 39.9% for chewing habits and 23.0% for alcohol drinking. Tobacco smoking, chewing habits, and alcohol drinking might be responsible for 85.3% of HNC cases. Individuals who smoked tobacco, chewed products and drank alcohol had a 13-fold increase in HNC risk (OR: 12.83; 95% CI: 6.91, 23.81) compared to individuals who did not have any of these habits. Both high frequency and long duration of these habits were strong risk factors for HNC among the Nepalese with clear dose-response trends. Preventive strategies against starting these habits and support for quitting these habits are necessary to decrease the incidence of HNC in Nepal.

Occupations and the Risk of Head and Neck Cancer: A Pooled Analysis of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

OBJECTIVE: To investigate the associations between head and neck cancer (HNC) risk and occupations. METHODS: We harmonized data on occupations in a pooled analysis of 8839 HNC cases and 13,730 controls in International Head and Neck Cancer Epidemiology (INHANCE) consortium. Logistic regression was used to estimate odds ratios (ORs) for associations of occupations and HNC risk. Population attributable fraction (PAF) for occupations was calculated using the formula PEC × (OR - 1)/OR. RESULTS: Trend of increasing HNC risk was found with increasing duration of employment for many occupations, including cooks (OR = 1.36; 95% confidence interval [CI] 1.09 to 1.68), cleaners (OR = 1.38; 95% CI 1.13 to 1.69), painters (OR = 1.82; 95% CI 1.42 to 2.35). The PAF for a priori occupations was 14.5% (95% CI 7.1% to 21.9%) for HNC. CONCLUSIONS: We found associations between certain occupations and HNC risks, including for subsites, with a duration-response relationship.

Body mass index and the risk of head and neck cancer in the Chinese population.

OBJECTIVE: To investigate potential associations between body mass index (BMI) and head and neck cancer (HNC) risk in an East Asian population. METHODS: We conducted a hospital-based multicenter case-control study in East Asia including 921 cases and 806 controls. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CI) for HNC risks by using logistic regression, adjusting on potential confounders. RESULTS: Compared to normal BMI at interview (18.5-<25 kg/m2), being underweight (BMI < 18.5 kg/m2) was associated with a higher HNC risk (OR = 2.71, 95% CI 1.40-5.26). Additionally, obesity (BMI > 30 kg/m2) was associated with a lower HNC risk (OR = 0.30, 95% CI 0.16-0.57). Being underweight at age 20 was also associated with an increased risk of HNC. However, being underweight at 5 years or 2 years before interview was not associated with a higher risk of HNC. CONCLUSION: We observed an inverse association between BMI and HNC risk, which is consistent with previous studies in other geographic regions. Being underweight at age 20 was also associated with a higher risk of HNC, suggesting that reverse causality was not the main source of the association.

Involuntary smoking and the risk of head and neck cancer in an East Asian population.

BACKGROUND: Although tobacco involuntary smoking is an established risk factor for lung cancer, the association with head and neck cancer (HNC) is not established. We aimed to investigate this potential association in an East Asian population. METHODS: We conducted a multicenter case-control study in East Asia including eight centers. We restricted our analysis to never tobacco smokers (303 cases and 459 controls) and to never tobacco smokers/never alcohol drinkers (243 cases and 403 controls). RESULTS: Among never tobacco smokers, involuntary smoking was associated with a 1.47-fold increase in risk of HNC (95%CI = 1.02, 2.13) and a 1.8-fold increase in the risk of oral cavity cancer (95%CI = 1.14, 2.92). Among never tobacco smokers who were also never alcohol drinkers, increased risks were detected for more than 3 h per day of involuntary smoking exposure and for 15 or more years of exposure. A dose-response relation was suggested for frequency of exposure (p for trend = 0.014) and for years of exposure (p for trend = 0.010) for oral cavity cancer. We did not detect strong increases in the risk of the other HNC subsites. CONCLUSIONS: Our study supports the association between involuntary smoking and the risk of HNC. The association may be stronger for oral cavity cancer than for other HNC subsites.

Fiber intake and the risk of head and neck cancer in the prostate, lung, colorectal and ovarian (PLCO) cohort.

Although the protective role of dietary fiber on cancer risk has been reported in several epidemiological studies, the association of fiber intake on head and neck cancer (HNC) risk is still unclear. We investigated the association between fiber intake and the risk of HNC using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Among 101,700 participants with complete dietary information, 186 participants developed HNC during follow-up (January 1998 to May 2011). Dietary data were collected using a self-administered food-frequency questionnaire (1998-2005). We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CI), using the Cox proportional hazards model. Higher intake of total fiber, insoluble fiber and soluble fiber was associated with decreased HNC risks, with a significant trend. The HRs of highest vs. the lowest tertile of intake were 0.43 (95%CI: 0.25-0.76) for total fiber, 0.38 (95%CI: 0.22-0.65) for insoluble fiber, and 0.44 (95%CI: 0.25-0.79) for soluble fiber. These inverse association were consistent in oral cavity and pharyngeal cases, but the impact of fiber intake was weaker in laryngeal cases. We did not observe any significant interaction of potential confounders, including smoking and drinking, with total fiber intake on HNC risk. These findings support evidence of a protective role of dietary fiber on HNC risk.

Tobacco smoking, alcohol drinking, betel quid chewing, and the risk of head and neck cancer in an East Asian population.

BACKGROUND: The smoking prevalence among men in China is high, but the head and neck cancer incidence rates are low. This study's purpose was to investigate the impact of tobacco, betel quid, and alcohol on head and neck cancer risk in East Asia. METHODS: A multicenter case-control study (921 patients with head and neck cancer and 806 controls) in East Asia was conducted. The odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. RESULTS: Head and neck cancer risks were elevated for tobacco (OR = 1.58), betel quid (OR = 8.23), and alcohol (OR = 2.29). The total attributable risk of tobacco and/or alcohol was 47.2%. Tobacco/alcohol appeared to account for a small proportion of head and neck cancer among women (attributable risk of 2.2%). Betel quid chewing alone accounted for 28.7% of head and neck cancer. CONCLUSIONS: Betel quid chewing is the strongest risk factor for oral cavity cancer in this Chinese population. Alcohol may play a larger role for head and neck cancer in this population than in European or U.S.

Shared and Study-specific Dietary Patterns and Head and Neck Cancer Risk in an International Consortium.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study.

BACKGROUND: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. METHODS: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. RESULTS: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). CONCLUSIONS: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.

Racial differences in the relationship between tobacco, alcohol, and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE Consortium.

There have been few published studies on differences between Blacks and Whites in the estimated effects of alcohol and tobacco use on the incidence of head and neck cancer (HNC) in the United States. Previous studies have been limited by small numbers of Blacks. Using pooled data from 13 US case-control studies of oral, pharyngeal, and laryngeal cancers in the International Head and Neck Cancer Epidemiology Consortium, this study comprised a large number of Black HNC cases (n = 975). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for several tobacco and alcohol consumption characteristics. Blacks were found to have consistently stronger associations than Whites for the majority of tobacco consumption variables. For example, compared to never smokers, Blacks who smoked cigarettes for > 30 years had an OR 4.53 (95% CI 3.22-6.39), which was larger than that observed in Whites (OR 3.01, 95% CI 2.73-3.33; pinteraction < 0.0001). The ORs for alcohol use were also larger among Blacks compared to Whites. Exclusion of oropharyngeal cases attenuated the racial differences in tobacco use associations but not alcohol use associations. These findings suggest modest racial differences exist in the association of HNC risk with tobacco and alcohol consumption.

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort.

BACKGROUND: Although low levels of folate leads to disturbances in DNA replication, DNA methylation and DNA repair, the association between dietary folate intake and head and neck cancer (HNC) risk remains unclear. METHODS: We evaluated the association between folate intake and HNC risk using prospective cohort data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. This study included 101 700 participants and 186 cases with confirmed incident HNC. The median follow-up was 12.5 years. We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) using Cox proportional hazard model including age, sex, body mass index, education, race, tobacco smoking, alcohol drinking and total fruit and vegetable intake. RESULTS: Higher intake of food folate and fortified folic acid in foods was associated with a decreasing HNC risk in a dose-response manner. The HRs of highest vs the lowest quartile of intake were 0.35 (95%CI: 0.18-0.67) for food folate, and 0.49 (95%CI: 0.30-0.82) for fortified folic acid. Intakes of total folate, natural folate and supplemental folic acid were not associated with the risk of HNC and its subsites. We did not detect any interaction between smoking, drinking and food folate intake on HNC risk. CONCLUSIONS: These findings provide evidence of the protective role of dietary folate intake on HNC risk.

Impact of oral hygiene on head and neck cancer risk in a Chinese population.

BACKGROUND: Although the impact of oral hygiene on head and neck cancer risk has been investigated, few studies have been conducted among the Asian population. METHODS: We conducted a multicenter case-control study to investigate this potential association. We performed unconditional multiple logistic regression models adjusted by potential confounders. RESULTS: We observed an inverse association of frequency of dental visits with head and neck cancer risk, with an adjusted odds ratio (OR) of 3.70 (95% CI 2.51-5.45) for never dental visits compared with ≥1 time/year (Ptrend < .001). We also observed a positive association between the number of missing teeth and head and neck cancer risk, with an adjusted OR for ≥5 missing teeth compared with <5 missing teeth of 1.49 (95% CI 1.08-2.04). Combining multiple oral hygiene indicators, poor oral hygiene scores increased head and neck cancer risk. CONCLUSION: Poor oral hygiene may increase head and neck cancer risk in the Chinese population. Therefore, improving oral hygiene may contribute to reducing the head and neck cancer risk in the Chinese population.

Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk.