Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection.

BACKGROUND: The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series. METHODS: This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan-Meier method and Cox regression. RESULTS: Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative. CONCLUSION: Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma.

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.

Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

Do tobacco and alcohol modify protective effects of diet on oral carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma.

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.

[Consumption of animal-derived foods and mouth and oropharyngeal cancer]. / Consumo de alimentos de origem animal e câncer de boca e orofaringe.

OBJECTIVE: Evaluate the relationship between animal-derived foods and mouth and oropharyngeal cancer. METHODS: Hospital-based case-control study matched by sex and age (± 5 years) with data collected between July of 2006 and June of 2008. The sample contained 296 patients with mouth and oropharyngeal cancer and 296 patients without a cancer history who were treated in four hospitals in the City of São Paulo, State of São Paulo, Brazil. A semistructured questionnaire was administered to collect data regarding socioeconomic condition and harmful habits (tobacco and alcoholic beverage consumption). To assess eating habits, a qualitative questionnaire that asked about the frequency of food consumption was used. The analysis was rendered by means of multivariate logistic regression models that considered the existing hierarchy among the characteristics studied. RESULTS: Among foods of animal origin, frequent consumption of beef (OR = 2.73; CI95% = 1.27-5.87; P < 0.001), bacon (OR = 2.48; CI95% = 1.30-4.74; P < 0.001) and eggs (OR = 3.04; CI95% = 1.51-6.15; P < 0.001) was linked to an increased risk of mouth and oropharyngeal cancer, in both the univariate and multivariate analyses. Among dairy products, milk showed a protective effect against the disease (OR = 0.41; CI95% = 0.21-0.82; P < 0.001). CONCLUSIONS: This study affirms the hypothesis that animal-derived foods can be etiologically linked to mouth and oropharyngeal cancer. This information can guide policies to prevent these diseases, generating public health benefits.

Cumulative coffee consumption and reduced risk of oral and oropharyngeal cancer.

We examined the association between coffee consumption and oral cancer in a hospital-based case-control study comprising 143 patients with oral and oropharyngeal squamous cell carcinoma attended at 3 major hospitals in Sao Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals and matched with cases by sex and age. Associations were assessed by multivariate logistic regression conditioned on sociodemographic and behavioral characteristics. Tobacco smoking, alcohol drinking, and higher intake of bacon and deep-fried foods were directly related to disease; the inverse was observed to family income and salad intake. Coffee consumption and tobacco smoking were partially correlated (Spearman correlation coefficient 0.14 among cases, 0.31 among controls). When adjusted for all covariates, a cumulative coffee consumption higher than 18.0 daily liters × year during lifetime was indicated to be protective against disease (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.94, P = 0.037). This observation may have pharmacological implications for clinical medication of these cancers and is relevant to programs aimed at reducing the burden of disease.

Polymorphisms in alcohol metabolizing genes and the risk of head and neck cancer in a Brazilian population.

AIMS: The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. METHODS: A hospital-based case-control study was conducted in São Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. RESULTS: Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol >30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11). CONCLUSIONS: The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655 g/L/day.

Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior.

The recent reclassification of a follicular variant of papillary thyroid carcinoma (FVPTC), subset as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), aims to avoid overtreatment of patients with an indolent lesion. The diagnosis of NIFTP has recently been revisited using more rigid criteria. This study presents histological and molecular findings and a long clinical follow-up of 94 FVPTC, 40 cases of follicular adenoma (FTA) and 22 cases of follicular carcinoma (FTC) that were classified before the advent of the NIFTP reclassification. All slides were reviewed using these rigid criteria and analysis of numerous sections of paraffin blocks and reclassified as 7 NIFTPs, 2 EFVPTCs, 29 infiltrative FVPTC (IFVPTCs), 57 invasive EFVPTC (I-EFVPTCs), 39 FTAs and 22 FTCs. Remarkably, EFVPTC and NIFTP patients were all free of disease at the end of follow-up and showed no BRAF mutation. Only one NIFTP sample harbored mutations, an NRAS Q61R. PAX8/PPARG fusion was found in I-EFVPTCs and FTC. Although additional studies are needed to identify a specific molecular profile to aid in the diagnosis of lesions with borderline morphological characteristics, we confirmed that the BRAF V600E mutation is an important tool to exclude the diagnosis of NIFTP. We also show that rigorous histopathological criteria should be strongly followed to avoid missing lesions in which more aggressive behavior is present, mainly via the analysis of capsule or vascular invasion and the presence of papillary structures.

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.

AIMS: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. METHODS AND RESULTS: We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. CONCLUSION: JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.

How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis?

BACKGROUND: Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC. METHODS: Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at x200 magnification. RESULTS: D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011). CONCLUSION: LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation.

Functional study of the voice and swallowing following supracricoid laryngectomy.

UNLABELLED: To identify the grade and evolution of dysphagia and dysphonia in patients undergoing supracricoid laringectomy, and to study the association of these findings with clinical and surgical variables. METHOD: The study included 22 cases undergoing supracricoid laringectomy at the Head and Neck Surgery and Otolaryngology Department of the Heliopolis Hospital - Brasil, and referred to speech therapy. Dysphagia and dysphonia were correlated with gender, age, stage T (T1, T2, T3, T4), primary site (supraglottis, glottis or subglottis), preservation of one or two arytenoids, reconstructive procedures (cricohyoidopexy or cricohyoidoepiglotopexy), time to withdraw the naso-enteral tube, and time to close the tracheostomy. Statistical tests included the Chi-square and/or Fischers exact test. RESULT: We observed an association between moderate grade dysphagia and the glottis as the primary site, cricohyoidoepiglotopexy as the type of reconstruction and naso-enteral tube removal within one month after the surgery. There was also an association between severe dysphagia and the supraglottis as the primary site. Dysphagia and dysphonia were associated in the degree of severity; however a larger number of patients had better progression of dysphagia compared to the progression of dysphonia. There was no statistical significance between other associations. CONCLUSION: Improvement of swallowing is more frequent than improvement of dysphagia. There is an association between moderate dysphagia and the glotttis as primary site, cricohyoidoepiglotopexy and naso-enteral tube removal within one month after surgery.

Diabetes mellitus, metformin and head and neck cancer.

INTRODUCTION: Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated with some cancers. However, studies on the association between diabetes mellitus and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial results. The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC. MATERIAL AND METHODS: This case-control study was conducted within the framework of the Brazilian Head and Neck Genome Project in 2011-2014. The study included 1021 HNC cases with histologically confirmed squamous cell carcinoma of the head and neck admitted to five large hospitals in São Paulo state. A total of 1063 controls were selected in the same hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. RESULTS: Diabetic participants had a decreased risk of HNC (OR=0.68; 95% CI: 0.49-0.95) than non-diabetic participants, and this risk was further decreased among diabetic metformin users (OR=0.54; 95% CI: 0.29-0.99). Diabetic metformin users that were current smokers (OR=0.13; 95% CI: 0.04-0.44) or had an alcohol consumption of >40g/day (OR=0.31; 95% CI: 0.11-0.88) had lower risk of HNC than equivalent non-diabetic participants. CONCLUSION: The risk of HNC was decreased among diabetic participants; metformin use may at least partially explain this inverse association.

Expression profile of malignant and non-malignant diseases of the thyroid gland reveals altered expression of a common set of genes in goiter and papillary carcinomas.

Using cDNA microarrays with 3800 cDNA fragments, we determined the expression profile of normal thyroid tissue, goiter, adenoma and papillary carcinoma (10 samples from each class). After background correction and statistical analysis, we identified a set of 160 genes as being differentially expressed in all pair-wise comparisons. Here we demonstrate that, at least on the basis of these differentially expressed genes, a positive correlation between goiter and papillary carcinomas could be observed. We identified a common set of genes whose expression is diminished in both goiter and papillary carcinomas as compared to normal thyroid tissue. Moreover, no genes with inverse correlation in samples from goiter and papillary carcinomas could be detected. Using Real-Time PCR and/or tissue microarrays, we confirmed the altered expression of some of the identified genes. Of notice, we demonstrate that the reduced mRNA levels of p27(kip1) observed in papillary carcinomas as compared to either goiter or normal thyroid tissues (P<0.001) is accompanied by an altered protein distribution within the cell. In papillary carcinomas, P27(KIP1) is preferentially cytoplasmic as opposed to goiter or normal thyroid tissue, where P27(KIP1) is preferentially located in the nucleus. The exploitation of the data presented here could contribute to the understanding of the molecular events related to thyroid diseases and gives support to the notion that common molecular events might be related to the frequent observation of areas of papillary carcinomas in the gland of patients with goiter.

[Relationship between the outcome and the frequency of micronuclei in cells of patients with oral and oropharyngeal carcinoma]. / Correlação entre a evolução clínica e a freqüência de micronúcleos em células de pacientes portadores de carcinomas orais e da orofaringe.

BACKGROUND: To verify the correlation between the micronucleus frequency and the presence of local recurrences or second primary lesion in patients with carcinoma of the oral cavity. METHODS: We studied the frequency of micronucleus of the oral mucosa in 27 untreated patients with carcinoma of the oral cavity and oropharynx. The patients were monthly followed after initial treatment, in an attempt to identify local recurrences or second primary lesions. RESULTS: Of the 24 patients evaluated during the whole time, 5 cases (20,8%) were alive and free of disease, and 19 cases died, 18 (75%) owing to cancer and 1 to perfurative peptic ulcer. In relation to micronucleus frequency, no difference was observed among the patients with local recurrence of the disease (N=14) and the patients who died of other causes or were alive and free of disease (N=10) (p = 0.83). There was higher micronucleus frequency in the stages T3 and T4 (p = 0.01). CONCLUSION: In the present study was not possible to find a clinical correlation between the frequency of micronucleus of the oral mucosal and the risk of development of local recurrence or second primary tumor in patients with upper aerodigestive tract carcinoma.

Serum and salivary macrophage migration inhibitory factor in patients with oral squamous cell carcinoma.

The overexpression of macrophage migration inhibitory factor (MIF) has been identified in a variety of tumors and the investigation of its molecular mechanisms in tumor progression is a key topic of research. The present study aimed to investigate MIF as a potential marker for disease control or recurrence, and to assess the association between serum and salivary MIF and the clinicopathological characteristics of patients with oral squamous cell carcinoma (OSCC). Serum and salivary samples were collected prior to and following the surgical treatment of 50 patients with OSCC. MIF concentrations were assessed by enzyme-linked immunosorbent assay and the adopted level of statistical significance was P<0.05. The results revealed that serum MIF concentrations were significantly reduced following tumor resection in OSCC patients. Furthermore, higher preoperative salivary MIF concentrations were observed in patients with larger tumors and in those who succumbed to the disease. In conclusion, high salivary and serological MIF concentrations were identified in patients with OSCC. Nevertheless, only serological MIF concentrations may be considered as a potential marker for the early detection of OSCC recurrence once the salivary levels, prior and following treatment, do not show any significant differences.

HIF-1alpha expression profile in intratumoral and peritumoral inflammatory cells as a prognostic marker for squamous cell carcinoma of the oral cavity.

The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker.

Are recurrent denture-related sores associated with the risk of oral cancer? A case control study.

OBJECTIVES: This study aimed to assess the hypothesis that recurrent denture-related sores association may be associated with the risk of oral cancer. METHODS: We conducted a hospital-based case-control study comprising 71 new cases of oral cancer in two hospitals in São Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals. All cases had histologically confirmed squamous cell carcinoma in anatomic sites of the mouth that may be specifically consi-dered at risk of sores by ill-fitting dentures. Denture-related sores were assessed by the self-report of recurrent oral sores due to the use of ill-fitting complete removable dental prosthesis. Associations were assessed by multivariate logistic regression conditioned on socio-demographic and behavioral characteristics. RESULTS: The association between ill-fitting dentures and oral cancer was statistically significant in the multivariate model: odds ratio 3.98; 95% confidence interval 1.06 - 14.96. The specific assessment of association between tumors in the lower jaw and sores by mandibular dentures confirmed this result: odds ratio 6.39; 95% confidence interval 1.49 - 29.52. CONCLUSION: The potential contribution of denture-related sores to oral carcinogenesis still fuels controversies. This study reinfor-ces the hypothesis that recurrent denture-related sores may be associated with the risk of oral cancer. Results reported here also suggest that an appropriate application and monitoring of dental prosthesis represent a non-negligible scope for cancer prevention.

FAS/FASL expression profile as a prognostic marker in squamous cell carcinoma of the oral cavity.

FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control.