Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1-3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4-7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

Evaluation of a new score associated with acute kidney injury in patients treated with cisplatin based EXTREME regimen.

BACKGROUND: This study evaluates the association of diuresis and hydration through a new monitoring indicator called U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. METHODS: We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. RESULTS: Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. CONCLUSION: The combination of diuresis and i.v. hydration through the U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI.

Occupational arsenic exposure and digestive and head and neck cancers: A systematic review and meta-analysis.

Arsenic is a known carcinogen for the lungs, the bladder, and the skin, while systematic evidence on other cancer types is lacking, especially for occupational exposure. Thus, we aimed to systematically summarize current evidence on the association between occupational arsenic exposure and digestive cancers, including head and neck cancer (HNC). We conducted a systematic review on Pubmed, Web of Science, and Embase search engines. We computed pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) using DerSimonian and Laird random-effects model. Occurrence of publication bias was assessed using contour-enhanced funnel plots and Egger's test. Twenty-two studies on digestive cancers and 11 on HNC were included in the meta-analysis. RRs for the association with occupational exposure to arsenic of 1.23 (95% CI: 1.07-1.40; I2 = 72.3%, p < 0.001) and 1.08 (95% CI: 0.76-1.53; I2 = 76.6%, p < 0.001) for digestive cancer and HNC, respectively, were observed. As for specific cancer types, arsenic was associated with rectal cancer (RR: 1.51; 95% CI: 1.003-2.28; I2 = 37.0%, p = 0.174), but not with other investigated cancer types. No clear evidence of publication bias was found. The results of our study suggest that the observed association between occupational arsenic exposure and digestive cancer might be mainly driven by a positive association for rectal cancer, while arsenic exposure did not appear to be associated with HNC. However, further high-quality studies with detailed assessment of arsenic exposure are warranted to clarify the potential association of arsenic with digestive cancers and HNC.

Risk Factors of Cetuximab-Induced Hypomagnesemia and the Effect of Magnesium Prophylaxis in Patients with Head and Neck Cancer: A Retrospective Study.

Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.

A Retrospective Service- Evaluation of Implant Success, Survival, Periimplant Health and Prosthetic Complications in a Cohort of Head and Neck Cancer Patients.

OBJECTIVES: To determine the success, survival, peri-implant health and prosthetic complications in head and neck cancer patients receiving oral rehabilitation utilising dental implants between 2008 and the present day. MATERIALS AND METHODS: Service evaluation. Survival Group: Retrospective review of records to determine implant survival and prosthetic complications. Success Group: Examination to determine implant success and health. RESULTS: Survival Group: 260 implants in 81 individuals, median follow up 49.2 months. 89.3% implant survival at 96 months, no further failures up to 133 months. 40.9% individuals required repair or remake of prosthesis by 72 months - mostly denture re-lines. Success group: 164 implants in 48 individuals, median follow up 56 months. Peri-implant mucositis detected in 22% of fixtures (37.5% individuals); peri-implantitis in 12.8% (25% individuals); 33.3% fixtures exhibiting periimplantitis at 120 months. Previous smoking significantly associated with development of peri-implantitis (HR 2.372, p=0.032, 95CI:1.232, 93.317). Compromised survival (e.g. peri-implantitis), absolute (not in mouth) or clinical failure estimated to occur in 28.1% fixtures at 101 months, mostly due to peri-implantitis. CONCLUSIONS: There is a large burden of ongoing care in this cohort, requiring interventions to improve peri-implant health and maintain complex prostheses. Oral rehabilitation and ongoing maintenance in this cohort is complex and multi-disciplinary.

Modulation of the oral glucocorticoid system during black raspberry mediated oral cancer chemoprevention.

Recent reports suggest that glucocorticoids (GCs), which can be synthesized in the oral mucosa, play an important role in cancer development. Therefore, the objectives of this study were to characterize the role of the oral GC system in oral cancer, and determine the effect of black raspberry (BRB) administration on GC modulation during oral cancer chemoprevention. We determined the expression of GC enzymes in various oral cancer cell lines, and investigated the role of the GC inactivating enzyme HSD11B2 on CAL27 oral cancer cells using siRNA mediated knockdown approaches. Using two in vivo models of oral carcinogenesis with 4-nitroquinoline 1-oxide carcinogen on C57Bl/6 mice and F344 rats, we determined the effect of BRB on GC modulation during head and neck squamous cell carcinoma chemoprevention. Our results demonstrate that HSD11B2, which inactivates cortisol to cortisone, is downregulated during oral carcinogenesis in clinical and experimental models. Knockdown of HSD11B2 in oral cancer cells promotes cellular proliferation, invasion and expression of angiogenic biomarkers EGFR and VEGFA. An ethanol extract of BRB increased HSD11B2 expression on oral cancer cells. Dietary administration of 5% BRB increased Hsd11b2 gene and protein expression and reduced the active GC, corticosterone, in cancer-induced mouse tongues. Our results demonstrate that the oral GC system is modulated during oral carcinogenesis, and BRB administration upregulates Hsd11b2 during oral cancer chemoprevention. In conclusion, our findings challenge the use of synthetic GCs in head and neck cancer, and support the use of natural product alternatives that potentially modulate GC metabolism in a manner that supports oral cancer chemoprevention.

PARP5B is required for nonhomologous end joining during tumorigenesis in vivo.

Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. Cancers with homologous recombination defects are sensitive to small molecule PARP inhibitors. Despite PARP5B gene copy number changes in many cancers, the effects of this genetic alteration on tumor phenotype are largely unknown. To better understand this clinical finding, we characterized a PARP5B null mutation in a carcinogen-induced in vivo head and neck squamous cell carcinoma (SCC) model. Reduced PARP5B expression inhibited tumor growth, induced primary tumor differentiation and apoptosis, and inhibited cell proliferation and metastasis. Loss of PARP5B expression-induced ataxia telangiectasia and Rad3 related (ATR) activation and depleted the cancer stem cell fraction. PARP5B null tumor cells lacked 53BP1+ double-strand break foci, ATM activation, and p53 induction compared to PARP5B+/+ cancers. PARP5B null SCC expresses a multiprotein complex containing PML, pRPA, Rad50, Rad51, XRCC1, proliferating cell nuclear antigen (PCNA), and Mcm2, suggesting an HR-mediated repair mechanism at DNA replication foci. Low doses of etoposide combined with the PARP5B inhibitor XAV939 induced senescence and apoptosis in human SCC lines. NBS1 overexpression in these cells inhibited the effects of low-dose etoposide/XAV939 treatment. Our results indicate that PARP5B inhibition is new targeted cancer therapy.

Drug-Eluting Embolics Chemoembolization for the Management of Recurrent or Advanced Head and Neck Cancer.

PURPOSE: To characterize the safety, tolerability, and efficacy of chemoembolization using drug-eluting embolic (DEE) microspheres in patients with recurrent and advanced head and neck cancer. MATERIALS AND METHODS: In this retrospective study, 32 patients (mean age, 57.2 years ± 2.8; 17 women) with recurrent (n = 16) and advanced (n = 16) head and neck cancer were treated with chemoembolization using DEE microspheres loaded with doxorubicin. Treatment response, overall survival, local progression-free survival, and adverse events were evaluated. RESULTS: At 6 months after the procedure, the objective response and disease control rates were 25% and 69%, respectively. The median overall survival and local progression-free survival were 14.5 and 13.6 months, respectively. Seven (22%) patients experienced adverse events after the chemoembolization procedure. All the adverse events were related to postembolization syndrome, including vomiting and nausea (n = 1), pyrexia (n = 2), and localized pain (n = 7). No severe adverse events or procedure-related deaths were observed. CONCLUSIONS: Chemoembolization using DEE microspheres was safe and tolerable in patients with recurrent and advanced head and neck cancer.

Topical Xerostomia Treatment with Hyaluronate Sheets Containing Pilocarpine.

Sjogren's syndrome and radiation therapy for head and neck cancers are often accompanied by xerostomia. Oral pilocarpine (PCP) to treat xerostomia produces systemic side effects, such as runny nose and lacrimation. To improve the therapeutic efficacy of PCP and reduce the aforementioned side effects, we developed a topical delivery system for PCP using freeze-dried sheets of hyaluronic acid (HA). The advantages of HA sheets over conventional oral formulations were examined through in vivo pharmacokinetic and pharmacodynamic studies after their application to oral tissues and salivary glands. The concentration of PCP in the submucosal tissue of the oral cavity was determined using the microdialysis (MD) method after buccal application of HA sheets containing PCP to hamsters. The concentration of PCP in the MD outflow was quite low after gastric administration, whereas the PCP concentration in plasma was high. In contrast, after buccal application of HA sheets containing PCP, the concentration of the drug in the MD outflow increased, despite the negligible concentration in plasma. These findings indicated that both enhancement of saliva secretion and the avoidance of systemic side effects could be achieved through buccal administration of PCP-loaded HA sheets. In addition, the pharmacodynamic study showed that when compared with intravenous and gastric administration, salivary application of HA sheets containing PCP resulted in similar volumes of saliva secretion and reduced lacrimal secretions. In conclusion, freeze-dried HA sheets allow for the development of a novel buccal delivery system with enhanced therapeutic efficacy and safety to treat xerostomia.

Effect of intravenous lidocaine on pain after head and neck cancer surgery (ELICO trial): A randomised controlled trial.

BACKGROUND: Treatment of postoperative pain after ear, nose and throat (ENT) cancer surgery is mainly morphine administration. Additional systemic lidocaine has shown promising results in some surgical procedures. OBJECTIVE: The main objective was to evaluate morphine consumption in the first 48 postoperative hours after intra-operative lidocaine infusion during major ENT cancer surgery. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Bicentric study including a university hospital and a major cancer centre, conducted from December 2016 to December 2019. PATIENTS: A total of 144 patients undergoing major ENT cancer surgery were included. INTERVENTION: The patients were randomly assigned to receive intravenous lidocaine or placebo during surgery and in the recovery room. MAIN OUTCOME MEASURES: Endpoints were postoperative morphine consumption in the first 24 and 48 h postoperatively, intra-operative remifentanil consumption, adverse events occurrence and assessment 3 to 6 months after surgery with the McGill pain questionnaire. RESULTS: A total of 118 patients were included (lidocaine n  = 57; placebo n  = 61, 26 patients were excluded). There was no significant difference in morphine consumption during the first 48 postoperative hours in the lidocaine group compared with the placebo group with a median [IQR] of 0.60 [0.30 to 1.03] mg kg -1 vs. 0.57 [0.37 to 0.96] mg kg -1 , total dose 44 [21 to 73.3] mg vs. 38 [23.3 to 56.5] mg, P  = 0.92.There was no significant difference between the two groups in any of the other endpoints, including at follow up 3 to 6 months after surgery. CONCLUSION: Intravenous lidocaine in ENT cancer surgery did not show any additional analgesic or morphine-sparing effect 48 h after surgery. Three to six months after surgery, there was no significant difference in pain scores or consumption of analgesics. Patients treated pre-operatively with opioids were not evaluated in the study. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02894710 and EUDRACT number 2015-005799-90.

Lack of association between dental implants and oral squamous cell carcinoma.

Design A systematic review of the literature to identify and evaluate the epidemiologic profile, and screen for possible risk factors and spectrum of clinical characteristics of oral squamous cell carcinoma (OSCC) surrounding dental implants, was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines.Data sources A search of two databases, Medline and CENTRAL, was undertaken, limited to articles published in English from the oldest records until 10 July 2018. Google Scholar was the grey literature searched. The references list in the included articles was assessed for further inclusion suitability.Study selection Participants included patients diagnosed with OSCC surrounding dental implants. The comparator or control was patients diagnosed with OSCC without dental implants. The outcome was epidemiology and carcinogenesis. The considered study designs were case reports, case series and retrospective studies. Article selection was performed by screening titles and abstracts individually by two blind review authors using the Rayyan platform based on the inclusion criteria. Then, the full text of the selected articles was assessed to identify the eligible articles, and the reasons for exclusion were reported. When a consensus was not achieved between the review authors, a third review author, who acted as a tiebreaker, was consulted.Data extraction Two independent review authors extracted the data using a specific extraction form in Microsoft Office Excel (Microsoft Corporation, Redmond, WA, USA). The extraction form consisted of authors, publication year, country, study design, number of cases, age, sex, risk factors, region of interest, the clinical aspect of the lesion, radiographic findings, the period between implant placement and tumour diagnosis, treatment, and follow-up. The time reported in the studies was converted to months for comparison. A third review author validated the accuracy of the information collected.Synthesis Two independent review authors assessed the risk of bias by applying the Joanna Briggs Institute (JBI) Critical Appraisal Checklist (CAP) for Case Reports and the JBI CAP for Prevalence Studies (for example, retrospective studies). Disagreements were resolved by consulting a third co-author. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) tool evaluated the certainty of the evidence of the main outcomes. A PRISMA flow diagram was presented, and a table summary of descriptive characteristics of the 33 included studies. Among the figures available, bar graphs represented the 'clinical features' according to the previous history of oral potentially malignant disorders and regarding the malignancy of oral potentially malignant disorders. In addition, a stacked line with markers represented the sex of the number of cases, displaying the time until diagnosis after implant placement and the time to disease progression.Data analysis A qualitative synthesis was provided. No quantitative data synthesis nor inter-rater agreement assessment was conducted.Results Thirty-one case reports and two retrospective studies, published between 1983 and 2020, met the eligibility criteria. The total sample consisted of 63 patients (male = 44.5%) with an average of 66.7 years (range = 42 to 90 years). Oral potentially malignant disorders were found in 29 patients (46%), of which 65.5% were female patients. The most common lesions were oral lichen planus and leukoplakia in female patients (52.6% and 31.5%) and male patients (20% and 60%). In 25 patients (39.6%), there was information missing about the presence of potentially malignant oral disorders, and oral hygiene status was reported in only 17.4% of the cases. Fifty-six patients (88.8%) of OSCC with dental implants were located in the mandible, and the most common clinical presentations of OSCC with implants were exophytic mass (46%) and ulceration (36.5%). Peri-implant bone loss assessment was performed in 51 patients (80.9%), of which 44 (86.2%) had peri-implant bone loss. Thus, most of these lesions were originally treated as peri-implantitis.Conclusions Most patients with OSCC next to their dental implants were female patients lacking known risk factors, and the common location was the mandible with an exophytic mass or ulceration presentation. A major concern is that the clinical and radiographic features of OSCC could be misdiagnosed as peri-implantitis. Thus, OSCC should be considered in persistent lesions surrounding dental implants. Several of the included reports were missing previous medical history and follow-up information. Hence, better case series and studies are required to support or reject the notion of an association between dental implants and OSCC.

Cell-free DNA and circulating tumor cell kinetics in a pre-clinical head and neck Cancer model undergoing radiation therapy.

BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis.

BACKGROUND: Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches. METHODS: High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool. RESULTS: The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells. CONCLUSION: The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.

The pesticides use and the risk for head and neck cancer: A review of case-control studies.

BACKGROUND: Tobacco, alcohol consumption, and HPV infection are the most common risk factors for head and neck cancer (HNC). Despite of this, recent evidences are growing on the association between long-term exposure to pesticides and the risk of chronic diseases, including different types of cancer. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of HNCs. MATERIAL AND METHODS: A literature search of the case-control studies was conducted in the PubMed, Web of science and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN 50) checklist. RESULTS: One thousand and thirty-five studies were identified and twelve met all criteria and, therefore, considered for quality assessment and data extraction. According to SIGN 50 criteria, six studies received an overall high-quality. All the studies considered of high quality found a positive association between exposure to pesticides and different HNC sites, including larynx, pharynx and nasal cavity. In addition, the increased risk was associated with the frequency of exposure. CONCLUSIONS: Finally, improving pesticide users' awareness of their risks and proper handling, as well as adopting protective measures such as the use of personal protective equipment, appear to be effective in reducing human health damage.

Validation of Alcohol Flushing Questionnaire to Identify ALDH2 Status in a Case-Control Study of Head and Neck Cancer.

BACKGROUND: Carriers of the ALDH2*2 allele have impaired alcohol metabolism and are more susceptible to the development of alcohol-related cancers, including head and neck cancer (HNC). Screening for ALDH2*2 allele may identify high-risk individuals for alcohol health education. Although genotyping of ALDH2 is the most accurate way to identify ALDH2 deficiency, it may not be practical due to the cost and requirement for genotyping service. METHODS: This study evaluated the accuracy of the alcohol flushing questionnaire to identify ALDH2 deficiency in a case-control study of HNC conducted in Taiwan using data collected from 904 patients with HNC and 1,078 controls. RESULTS: Overall, alcohol flushing questionnaire had a high sensitivity (89%) of identifying ALDH2*2 carriers among the control subjects and a good sensitivity (79%) among the patients with HNC. The sensitivity of the alcohol flushing questionnaire in identifying ALDH2*2 carriers was affected by alcohol use, with a lower sensitivity among individuals who consumed alcohol, particularly among current regular (drinking alcohol once per week or more) alcohol drinkers. CONCLUSIONS: The current validation study showed that the alcohol flushing questionnaire may be a reasonable method to identify ALDH2-deficient individuals. However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.

[Alcohol consumption and head and neck cancer]. / Consommation d'alcool et cancers ORL.

Alcohol is often considered as a simple co-factor, potentiating the carcinogenic effect of tobacco, in head and neck cancer. However, its own effect is less clear. It has been recognized by the International Agency for Research on Cancer (IARC) as a risk factor for head and neck cancer for many years. It seems that the risk is a function of the importance of consumption, with certain genetic predispositions. This risk can also decrease if consumption stops, with a prolonged interruption. In addition, alcohol consumption may have a negative influence on the prognosis of patients with this type of cancer. A preventive action is therefore essential, among other things via information to the patient provided by health providers.

En cancérologie ORL, l'alcool est souvent considéré comme un simple co-facteur, potentialisant l'effet carcinogène du tabac. Son effet propre est moins clair. Il est pourtant reconnu par le Centre International de Recherche sur le Cancer (CIRC) comme un facteur de risque de cancer ORL depuis de nombreuses années. Il semble que le risque soit fonction de l'importance de la consommation, avec la contribution de certaines prédispositions génétiques. Ce risque peut également diminuer en cas d'arrêt de la consommation, moyennant un arrêt prolongé. Par ailleurs, la consommation d'alcool pourrait avoir une influence néfaste sur le pronostic des patients atteints de ces cancers. Une action préventive est donc primordiale, entre autres interventions, via l'information du patient par le corps médical.

Pesticides as risk factors for head and neck cancer: A review.

Humans may be exposed to pesticides such as fungicides, herbicides, and insecticides, during occupational and non-occupational activities. Pesticides could be related to cancer development mainly because of their effects on the endocrine and immune systems and their cumulative effect. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of head and neck cancer (HNC). A literature search for cohort studies was conducted in the PubMed, Web of science, and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. One thousand one hundred and thirty-two studies were identified. Thirty-two were included. Most of the studies found addressed occupational exposure to pesticides and were conducted in Europe and North America. Eleven high-quality studies were found. Most of them found no association between exposure to pesticides and increased risk of HNC. Two studies found some evidence of a positive association between pesticide (malathion and atrazine) exposure and thyroid cancer. The literature review does not support a clear evidence for association between pesticides exposure and HNC. Only limited evidence points to a positive association between exposure to some pesticides and thyroid cancer. Further standardized studies based on appropriate designs are required to clarify the effect of pesticides on the genesis of HNC, considering dose, length of exposure, and type of pesticide.

Case-control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Occupational exposure to chlorinated solvents and risk of head and neck cancer in men: a population-based case-control study in France.

BACKGROUND: Few epidemiological studies have investigated the link between occupational exposure to solvents and head and neck cancer risk, and available findings are sparse and inconsistent. The objective of this study was to examine the association between occupational exposure to chlorinated solvents and head and neck cancer risk. METHODS: We analyzed data from 4637 men (1857 cases and 2780 controls) included in a population-based case-control study, ICARE (France). Occupational exposure to five chlorinated solvents (perchloroethylene [PCE], trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs) and confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos exposure, and other potential confounders. RESULTS: We observed no association between chlorinated solvent exposure and head and neck cancer risk, despite a non-significant increase in risk among subjects who had the highest cumulative level of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend = 0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI = 0.98 to 5.85). CONCLUSION: Our findings provide evidence that high exposure to PCE increases the risk of laryngeal cancer, and suggest an association between exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents was not associated with the risk of head and neck cancer.