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A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16 INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer., (© 2023 UICC.)

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC., (© 2018 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.)

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels., (© 2014 UICC.)

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables., (Copyright © 2013 UICC.)

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry., (Copyright © 2011 UICC.)

Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature., (Copyright © 2010 UICC.)

There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi-quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05-1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62-0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66-0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67-0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69-0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer.