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1.  Occupation and educational inequalities in laryngeal cancer: the use of a job index 
BMC Public Health  2013;13:1080.
Previous studies tried to assess the association between socioeconomic status and laryngeal cancer. Alcohol and tobacco consumption explain already a large part of the social inequalities. Occupational exposures might explain a part of the remaining but the components and pathways of the socioeconomic contribution have yet to be fully disentangled. The aim of this study was to evaluate the role of occupation using different occupational indices, differentiating between physical, psycho-social and toxic exposures and trying to summarize the occupational burden into one variable.
A population-based case–control study conducted in Germany in 1998–2000 included 208 male cases and 702 controls. Information on occupational history, smoking, alcohol consumption and education was collected with face-to-face interviews. A recently developed job-classification index was used to account for the occupational burden. A sub-index focussed on jobs involving potentially carcinogenic agents (CAI) for the upper aero digestive tract.
When adjusted for smoking and alcohol consumption, higher odds ratios (ORs) were found for lower education. This OR decreased after further adjustment using the physical and psycho-social job indices (OR = 3.2, 95%-CI: 1.5-6.8), similar to the OR using the sub-index CAI (OR = 3.0, 95%-CI: 1.4-6.5).
The use of an easily applicable control variable, simply constructed on standard occupational job classifications, provides the possibility to differentiate between educational and occupational contributions. Such an index might indirectly reflect the effect of carcinogenic agents, which are not collected in many studies.
PMCID: PMC4225569  PMID: 24246148
Laryngeal cancer; Education; Occupational indices; Exposure substance check list
2.  HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas 
The Journal of Clinical Investigation  2013;123(6):2488-2501.
High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compared with HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. HPV-related alterations were confirmed for the majority of candidate gene promoters by mass spectrometric, quantitative methylation analysis. There was a significant inverse correlation between promoter hypermethylation of ALDH1A2, OSR2, GATA4, GRIA4, and IRX4 and transcript levels. Interestingly, Kaplan-Meier analysis revealed that a combined promoter methylation pattern of low methylation levels in ALDH1A2 and OSR2 promoters and high methylation levels in GATA4, GRIA4, and IRX4 promoters was significantly correlated with improved survival in 3 independent patient cohorts. ALDH1A2 protein levels, determined by immunohistochemistry on tissue microarrays, confirmed the association with clinical outcome. In summary, our study highlights specific alterations in global gene promoter methylation in HPV-driven OPSCCs and identifies a signature that predicts the clinical outcome in OPSCCs.
PMCID: PMC3668826  PMID: 23635773
3.  Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1) 
BMC Cancer  2012;12:483.
Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer.
Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL −1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm.
Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression.
A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week.
Trial registration number
NCT01108042 ( Identifier)
PMCID: PMC3485626  PMID: 23083061
Docetaxel; Cisplatin; 5-fluorouracil; Locally advanced oral cancer; Surgery; Radiotherapy
4.  Definitive Radiotherapy versus Postoperative Radiotherapy of Patients with Oro- and Hypopharyngeal Cancer: Impact of Prognostic Factors 
Journal of Oncology  2012;2012:391917.
Purpose. To compare the impact of prognostic factors of patients treated with definitive radio(chemo)therapy versus patients treated with surgery and postoperative radiotherapy for squamous cell carcinoma of the oro- and hypopharynx. Patients and Methods. 162 patients treated with definitive radiotherapy and 126 patients treated with postoperative radiotherapy were retrospectively analysed. The impact of the prognostic factors gender, age, total tumor volume (TTV), pre-radiotherapy hemoglobin level (Hb-level), tumor site, T- and N-classification, radiotherapy interruptions >5 days, radiotherapy versus simultaneous radiochemotherapy, R-status and time interval between surgery and radiotherapy were investigated. Results. The median follow-up time for the censored patients treated with definitive radio(chemo)therapy was 28.5 months and for postoperative radiotherapy 36.5 months. On univariate analysis, the TTV, Hb-level, and simultaneous radiochemotherapy had a significant impact on the survival of patients treated with definitive radio(chemo)therapy. For patients treated with postoperative radiotherapy, only the TTV showed a statistical trend for the survival (P = 0.13). On multivariate analysis, the TTV and simultaneous radiochemotherapy maintained their statistical significance for patients treated with definitive raditherapy, and the TTV, the statistical trend for patients treated with postoperative radiotherapy (P = 0.19). Conclusions. The TTV was the predominant prognostic factor for both, patients treated with definitive or postoperative radiotherapy.
PMCID: PMC3270431  PMID: 22315594
6.  Intensity and Inhalation of Smoking in the Aetiology of Laryngeal Cancer 
The carcinogenic effect of smoking on laryngeal cancer is well established; however, the risk pattern for detailed smoking characteristics is less clear. Thus, the aim of this analysis was to quantify the impact of different inhalation behaviours on the risk of laryngeal cancer. We conducted a population-based case control study in Germany, frequency-matched for sex and age, using a standardized questionnaire covering lifelong smoking details, including age at start, time since quitting, types of smoking products, duration, intensity and inhalation behaviour. We found higher risks for increasing duration and intensity of smoking. A clear dose-response relationship was found in all inhalation subgroups, i.e., not only for deep inhalers, but also for those puffing on a cigarette. Clearly reduced risks could be observed for quitting smoking. Changing inhalation habits might be considered as a first step to reducing the risk of developing laryngeal cancer. However, the best way to effectively reduce laryngeal cancer risk is to quit smoking.
PMCID: PMC3118874  PMID: 21695025
laryngeal cancer; smoking, inhalation; smoking intensity; puffing; quitting smoking

Results 1-6 (6)