Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa front 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/ Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors. (C) 2004 Elsevier B.V. All rights reserved.

Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review

Chondrosarcoma (CHS) is a malignant neoplasm characterized by the formation of cartilaginous matrix by neoplastic cells, with a high propensity for local recurrences. Head and neck CHS is rare, accounting for less than 12% of all cases of CHS, usually affecting the maxilla. The majority of affected patients are in the fourth decade of life, with a slight predilection for male patients. A painless swelling is commonly the most frequent complaint. Surgery with wide en-bloc resection is the preferred treatment for CHS; radiotherapy and chemotherapy are usually palliative options. Owing to its rarity, there are few clinical series evaluating the biological behaviour of head and neck CHS. The aim of this study is to analyse the clinicopathological characteristics of head and neck CHS by reporting 3 new cases of this neoplasia affecting the jaw bones and reviewing the clinical series previously published in the English literature.

Analysis of the TAX1BP1 gene in head and neck cancer patients

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Distinct regions of loss of heterozygosity on 22q at different sites of head and neck squamous cell carcinomas

Background: Frequent loss of heterozygosity (LOH) has been reported in many types of cancer, including head and neck carcinomas. Somatic deletions involving specific chromosomal regions are strongly associated with inactivation of the allele of a tumor suppressor gene located within the deleted region. In most studies concerning LOH in head and neck squamous cell carcinomas (HNSCC) the different anatomical sites are not distinguished. The behavior of tumors arising at various sites differs significantly, however, suggesting different intrinsic tumor properties. In this study we compared the LOH on 22q and its relationship to clinicopathological parameters at the three major sites of HNSCC: oral cavity, larynx and pharynx. Material/Methods: LOH and microsatellite instability (MSI) were studied using seven polymorphic microsatellite markers mapped to the 22q11-q13.3 region in 37 oral, 32 laryngeal, and 31 pharyngeal carcinomas. Results: Two separate regions of LOH were identified in the laryngeal (22q11.2-12.1) and oral cavity (22q13.1-13.31) tumors. When the different anatomical sites were compared, a statistically significant difference was found between the presence of LOH at D22S421 (p<0.001), D22S315 (p=0.014) and D22S929 (p=0.026) in the laryngeal tumors. Conclusions: These data suggest that distinct regions on 22q are involved in LOH in oral cavity and laryngeal tumorigenesis but do not support a similar association between the development of pharyngeal tumors and genes located on 22q. These findings implicate the presence of different tumor suppressor genes mapping to distinct regions on chromosome 22q in oral and laryngeal carcinomas.

Influence of preventive dental treatment on mutans streptococci counts in patients undergoing head and neck radiotherapy

The aim of this study was to evaluate the influence of chlorhexidine gluconate, sodium fluoride and sodium iodine on mutans streptococci counts in saliva of irradiated patients. Forty-five patients were separated into three experimental groups and received chlorhexidine (0.12%), sodium fluoride (0.5%) or sodium iodine (2%), which were used daily during radiotherapy and for 6 months after the conclusion of the treatment. In addition, a fourth group, composed by 15 additional oncologic patients, who did not receive the mouthwash or initial dental treatment, constituted the control group. Clinical evaluations were performed in the first visit to dental clinic, after initial dental treatment, immediately before radiotherapy, after radiotherapy and 30, 60, 90 days and 6 months after the conclusion of radiotherapy. After clinical examinations, samples of saliva were inoculated on SB20 selective agar and incubated under anaerobiosis, at 37oC for 48 h. Total mutans streptococci counts were also evaluated by using real-time PCR, through TaqMan system, with specific primers and probes for S. mutans and S. sobrinus. All preventive protocols were able to reduce significantly mutans streptococci counts, but chlorhexidine gluconate was the most effective, and induced a significant amelioration of radiotherapy side effects, such as mucositis and candidosis. These results highlights the importance of the initial dental treatment for patients who will be subjected to radiotherapy for head and neck cancer treatment.

Head and neck carcinogenesis: Impact of MTHFD1 G1958A polymorphism

Objective: To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics. Methods: Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. Results: Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more ofen found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). Conclusion: Te presence of MTHFD1 G1948A polymorphism associated with smoking and alcoholism raises the head and neck cancer risk.

Invasive head and neck cutaneous squamous cell carcinoma: clinical and histopathological characteristics, frequency of local recurrence and metastasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Salivary and serum proteomics in head and neck carcinomas before and after surgery and radiotherapy

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.

PHF21B as a candidate tumor suppressor gene in head and neck squamous cell carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between head and neck cancer therapy and some genetic endpoints

Head and neck cancer (HNC) is the sixth most common human malignancy worldwide. The main forms of treatment for HNC are surgery, radiotherapy (RT) and chemotherapy (CT). However, the choice of therapy depends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells. Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is still the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in the oral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects.

Opportunistic microorganisms in patients with head and neck trauma

The use of antimicrobial agents has facilitated the dissemination of multi-resistant microorganisms, compromising dental and medical treatment. The aim of this study was to evaluate the distribution of different opportunistic microbial species in patients who suffered head and neck trauma, under temporary maintenance in nosocomial environment, particularly intensive care units, on the occurrence of such microorganisms in the oral cavity of the patients. It was selected 38 patients subjected to head and neck traumas. After emergency surgical procedures, clinical samples of saliva, sub and supragingival biofilms and mucosal surfaces were collected at two different moments: just after stabilization of the patient and soon after patients’ release from medical units. The presence of opportunistic and superinfecting microorganisms was evaluated by culture on selective and non-selective media, and the presence of the family Enterobacteriaceae, as well as genera Enterococcus, Pseudomonas, and Staphylococcus was assessed by PCR. It was found that the use of antimicrobials, even for short periods of time was sufficient to facilitate colonization by microorganisms of the families Enterobacteriaceae and Pseudomonadaceae, as well as yeasts and enterococci. These results support the concept that medical and dental teams should make a periodically change of antimicrobials used in treatment protocols in hospital for head and neck trauma patients, in order to minimize dissemination of opportunistic or superinfecting microorganisms.

Symptoms of depression in patients with cancer of the head and neck undergoing radiotherapy treatment: a prospective study

This study aimed to investigate the frequency of symptoms of depression in patients with cancer of the head and neck undergoing radiotherapy treatment, in the initial, middle and final stages of the treatment. This is a prospective exploratory quantitative study of 41 patients with head and neck cancer, undergoing radiotherapy treatment in the Oncology Outpatient Clinic of the Beneficencia Portuguese Hospital of Ribeirao Preto. Data were collected through the Beck Depression Inventory instrument, and analyzed quantitatively by means of the Statistical Package for the Social Sciences. Symptoms of dysphoria were found to increase throughout the treatment, as well as the number of patients with depression. The results show the importance for the healthcare professionals to detect the prevalence and the levels of the symptoms of depression, since these symptoms tend to increase and may lead to consequences such as a lack of adherence to treatment and a decrease in the quality of life of these patients.