Apoptosis in tongue squamous cell carcinoma and its correlation with clinically occult cervical metastasis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Prognostic significance of the number of lymph nodes in elective neck dissection for tongue and mouth floor cancers

The presence of metastatic lymph nodes is a relevant aspect in the treatment of head and neck cancer, bringing about a 50% reduction in survival. Objective: To assess the number of lymph nodes removed in the neck dissection and their relationship with the prognosis. Methods: A retrospective study involving 143 patients with tongue and mouth floor epidermoid carcinoma, which histological exam showed no lymph node metastases. Among those, 119 were males and 24 females, with mean age of 54 years. As to the primary tumor site, 65 were in the tongue and 78 in the mouth floor. T stage distribution was of four T1, 84 T2, 36 T3 and 19 T4. We carried out 176 neck dissections, unilateral in 110 cases and bilateral in 33. Of these, 78 were radical and 98 selective. The patients were broken down into three groups, according to the 33 and 66 percentiles of the number of lymph nodes resected. Results: The mean number of resected lymph nodes was 27; 24 in selective dissections and 31 in the complete ones. We did not have statistically significant differences when associated to the T and N stages. Conclusions: The larger number of lymph nodes dissected in the neck dissection identifies the group of better prognoses among pN0 cases.

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Analysis of Survival Rate and Independent Prognostic Factors in the Amazon Region

Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Although several studies have shown the epidemiology of this cancer in Brazil, there do not seem to be any studies that describe the prognostic factors related to OSCC in the Amazon region. Therefore, the aim of this study was to determine the survival rate and prognostic significance of different factors in patients from this region affected by OSCC. Data from 85 patients with histologically confirmed squamous cell carcinoma of the tongue and floor of the mouth identified from the Ofir Loyola Hospital archives were collected and analyzed using univariate (log-rank test) and multivariate (Cox proportional hazard model) tests. The overall 5-year survival rate was found to be 27%. Univariate analysis showed that the 5-year survival rate was significantly higher for younger (<= 45 y) female patients, patients with T1-2 tumors and clinically clear neck nodes (N0), patients with early stage cancers (AJCC stage I-II), and patients treated with surgical procedures. However, multivariate analysis showed that the 5-year survival rate was significantly higher only in the younger patients and those who underwent surgical treatment. The age of the patient at the moment of diagnosis and treatment with surgical procedures were the only independent prognostic factors that affected the 5-year survival rate of the patients in this region.

The reasons for discrepancies in target volume delineation : a SASRO study on head-and-neck and prostate cancers.

PURPOSE: To understand the reasons for differences in the delineation of target volumes between physicians. MATERIAL AND METHODS: 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. RESULTS: Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. CONCLUSION: These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins).

High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.

Histological and immunohistochemical study of the expression of p53 and ki-67 proteins in the mucosa of the tongue, pharynx and larynx of rats exposed to cigarette smoke

Introduction: Head and neck cancers are linked to smoking. The most affected sites are the oral cavity, pharynx and larynx. Experimental studies show epithelial lesions caused by cigarette smoke. Objectives: To investigate in rats the effects of acute cigarette smoke exposure on the mucosa of the tongue, pharynx and larynx.Material and method: Wistar rats were allocated into two groups of 20 animals: CG (control) receiving food and water ad libitum and TG (Tobacco) exposed to the smoke of 40 cigarettes/day for 60 days. Biopsy of their tongues, pharynxes and larynxes were subjected to histopathological, histomorphometric and immunohistochemical studies of protein p53 and ki-67.Result: The histological analysis of tongue from the Tobacco group revealed epithelial hyperplasia (90%), basal cell hyperplasia (95%) and mild to moderate dysplasia (85%). In pharynx showed basal cell hyperplasia (85%), dysplasia (25%) and vascular congestion (95%). In larynx showed basal cell hyperplasia (70%), epithelial hyperplasia (55%), congestion (100%) and inflammatory infiltrate (25%). Morphometric analysis revealed that keratin layer thickness was greater in the tobacco group. P53 immunoexpression was negative in both groups. Ki-67 immunoexpression was positive in basal cell nuclei but in parabasal cell nuclei it was positive only in the Tobacco group.Conclusions: The exposure of animals to cigarette smoke for 60 days resulted in benign lesions. The duration of exposure was not enough to cause the development cancer, as confirmed by the negative expression of p53 protein in all slides examined. Analysis of ki-67 expression showed intense epithelial proliferation in response to damage.

Stromal Myofibroblasts In Squamous Cell Carcinoma Of The Tongue In Young Patients - A Multicenter Collaborative Study.

The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against α smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal α smooth muscle actin expression, higher tumor grades or clinical stage (P > .05). There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.

[the New Classification Of Breast Cancers: Finding The Luminal A].

To compare the distributions of patients with clinical-pathological subtypes of luminal B-like breast cancer according to the 2011 and 2013 St. Gallen International Breast Cancer Conference Expert Panel. We studied 142 women with breast cancer who were positive to estrogen receptor and had been treated in São Paulo state, southeast Brazil. The expression of the following receptors was assessed by immunohistochemistry: estrogen, progesterone (PR) and Ki-67. The expression of HER-2 was measured by fluorescent in situ hybridization analysis in tissue microarray. There were 29 cases of luminal A breast cancers according to the 2011 St. Gallen International Breast Cancer Conference Expert Panel that were classified as luminal B-like in the 2013 version. Among the 65 luminal B-like breast cancer cases, 29 (45%) were previous luminal A tumors, 15 cases (20%) had a Ki-67 >14% and were at least 20% PR positive and 21 cases (35%) had Ki-67 >14% and more than 20% were PR positive. The 2013 St. Gallen consensus updated the definition of intrinsic molecular subtypes and increased the number of patients classified as having luminal B-like breast cancer in our series, for whom the use of cytotoxic drugs will probably be proposed with additional treatment cost.

Nodular Swelling Of The Tongue.

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Effectiveness of a new toothbrush design versus a conventional tongue scraper in improving breath odor and reducing tongue microbiota

For centuries, specific instruments or regular toothbrushes have routinely been used to remove tongue biofilm and improve breath odor. Toothbrushes with a tongue scraper on the back of their head have recently been introduced to the market. The present study compared the effectiveness of a manual toothbrush with this new design, i.e., possessing a tongue scraper, and a commercial tongue scraper in improving breath odor and reducing the aerobic and anaerobic microbiota of tongue surface. The evaluations occurred at 4 moments, when the participants (n=30) had their halitosis quantified with a halimeter and scored according to a 4-point scoring system corresponding to different levels of intensity. Saliva was collected for counts of aerobic and anaerobic microorganisms. Data were analyzed statistically by Friedman's test (p<0.05). When differences were detected, the Wilcoxon test adjusted for Bonferroni correction was used for multiple comparisons (group to group). The results confirmed the importance of mechanical cleaning of the tongue, since this procedure provided an improvement in halitosis and reduction of aerobe and anaerobe counts. Regarding the evaluated methods, the toothbrush's tongue scraper and conventional tongue scraper had a similar performance in terms of breath improvement and reduction of tongue microbiota, and may be indicated as effective methods for tongue cleaning.

Nerve endings of filliform, fungiform and vallate papillae of dorsal tongue mucosa of White-lipped peccary (Tayassu pecari): Neurohistological observations

The neurohistologic observations were performed using the specimens prepared by Winkelmann and Schmitt silver impregnation method. The tissues were fixed in 10% formalin solution and sections of 40µm thickness were obtained by Leica Cryostat at -30ºC. The sections of dorsal mucosa of White-lipped peccary tongue showed numerous filliform and fungiform papillae, and two vallate papillae on the caudal part. The epithelial layer revealed queratinized epithelial cells and the connective tissue papillae of different sizes and shapes. Thick nerve fiber bundles are noted into the subepithelial connective tissue of the papillae. The connective tissue of fungiform and vallate papillae contained numerous sensitive nerves fibers bundles forming a complex nerve plexus.

Body Mass Index, Cigarette Smoking, and Alcohol Consumption and Cancers of the Oral Cavity, Pharynx, and Larynx: Modeling Odds Ratios in Pooled Case-Control Data

study-specific results, their findings should be interpreted with caution

Prognostic index expression of cyclin-D1, cerbB-2 and VEGF: metastases vs corresponding primary cancers and metastatic vs non-metastatic adenocarcinomas

The prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin-D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers. Material and Methods: We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, c-erbB-2 and VEGF in 52 patients with surgically excised ademocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases. Results: Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression were also lower in metastases than in corresponding primary cancers, but this difference did not achieve statistical significance. Non-metastatic cancers also presented significantly lower Cyclin-D1 and c-erbB-2 expression than metastatic cancers (p<0.01 and p<0.01, respectively). Equally significant was the difference between higher c-erbB-2 expression by metastatic cancers compared to non-metastatic cancers (p=0.02). Considering survival in Kaplan-Maier analysis, Cyclin-D1 (p=0.04), c-erbB-2 (p=0.04) and VEGF (p<0.01) were important predictors of survival in metastatic cancers.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.