RESUMEN
BACKGROUND: A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. METHODS: We conducted a case-control study in São Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. RESULTS: Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. CONCLUSIONS: Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.
Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Disparidades en el Estado de Salud , Fumar/epidemiología , Clase Social , Anciano , Brasil/epidemiología , Intervalos de Confianza , Femenino , Neoplasias de Cabeza y Cuello/etiología , Humanos , Masculino , Persona de Mediana Edad , Ajuste de RiesgoRESUMEN
DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine's potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 microg naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals.
Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Proteínas de Choque Térmico/inmunología , Inmunoterapia/métodos , Vacunas de ADN/inmunología , Adulto , Anciano , Formación de Anticuerpos/inmunología , Vacunas contra el Cáncer/inmunología , Esquema de Medicación , Ensayo de Inmunoadsorción Enzimática , Femenino , Proteínas de Choque Térmico/genética , Humanos , Inmunidad Celular/inmunología , Masculino , Persona de Mediana Edad , Vacunas de ADN/genéticaRESUMEN
Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 microg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 microg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 microg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.
Asunto(s)
Proteínas Bacterianas/uso terapéutico , Carcinoma de Células Escamosas/terapia , Chaperoninas/uso terapéutico , Neoplasias de Cabeza y Cuello/terapia , Inmunoterapia/métodos , Vacunas de ADN/uso terapéutico , Adulto , Anciano , Proteínas Bacterianas/inmunología , Carcinoma de Células Escamosas/patología , Chaperonina 60 , Chaperoninas/inmunología , Estudios de Factibilidad , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunoterapia/efectos adversos , Masculino , Persona de Mediana Edad , Vacunas de ADN/inmunologíaRESUMEN
BACKGROUND: Parathyroid carcinoma is rare and represents 0.1% to 5% of the cases of hyperparathyroidism. New accounts are important to the understanding of these tumors. Experience in 9 cases is reported. METHODS: From 1970 to 1995, 10 patients with parathyroid carcinoma demonstrated by clinical course or pathologic features of malignancy were treated. The patient's clinical data, laboratory and imaging examinations, surgical findings, pathology, recurrences, and survival were analyzed. RESULTS: One male patient was excluded because of insufficient data. Average age was 51 years, with female:male ratio of 2:1. Average calcium level was 14,3 mg/dL. Palpable mass was found in 55%, bone disease in 89%, and renal disease in 78%. Four patients were reoperations. Five were operated on for hyperparathyroidism (1/tertiary). Capsular invasion was the most incident pathologic feature. Local recurrence occurred in 55%; neck node and bone metastasis in 11%, and lung in 33%. Two patients are alive and 5 died of disease. CONCLUSIONS: Parathyroid carcinoma has clinical and laboratory features that can help diagnosis at the first surgery. It seems to have variable malignancy.