Prevalence of human papillomavirus in saliva and cervix of sexually active women.

OBJECTIVE: Human papillomavirus (HPV) is strongly associated with cervical cancer and possibly with some oropharyngeal cancers. However, the relation between oral and cervical HPV infection is not fully understood. This study evaluates the prevalence rate and type-concordance of HPVs in these areas. METHODS: HPV DNA typing was performed in saliva and cervical specimens of 43 sexually active women, with the use of general consensus PCR and nested PCR (NPCR) tests. RESULTS: The prevalence rate of HPV DNA in cervical and saliva samples was 51.2% and 11.6% with general PCR, and 60.5% and 44.2% with NPCR, respectively. The probability of HPV DNA detection with general PCR in saliva was about 8 times lower compared to the cervix (P<0.001, OR: 0.13, 95% CI: 0.04-0.37), but showed no difference when the more sensitive NPCR method was applied (P=0.139, OR: 0.52, 95% CI: 0.22-1.21). The distribution of HPV variants according to their oncogenic potential revealed no statistically significant difference, regardless to the PCR method used for both sites. All general PCR HPV DNA positive saliva specimens belonged to women with cytology findings (n=5). These women had also 8.5 times higher risk for presenting with positive HPV detection in saliva with the NPCR method (P=0.009, OR=8.50, 95% CI: 1.74-39.70). CONCLUSIONS: Women with genital HPV infection are at higher risk for asymptomatic oral HPV infection. Prophylactic HPV-vaccination may reduce the burden of HPV-related diseases in both cervix and oropharynx.

Association study indicates combined effect of interleukin-10 and angiotensin-converting enzyme in basal cell carcinoma development.

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) - 1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 - 1082G (P = 0.019) and in ACE D (P = 0.003) in BCC patients in comparison to controls. Multivariate logistic regression models evaluated the contribution of homozygous and heterozygous variant polymorphisms to the risk for BCC development. The studied polymorphisms influencing the expression of IL-10 and ACE genes were recognized as potential predictive factors for BCC. These findings suggest a possible molecular mechanism leading to BCC development that is likely to involve the activation of angiotensin receptors in combination with increased plasma levels of IL-10 in patients.

Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months follow-up.

GOALS OF WORK: This is a prospective clinical study aimed at assessing the success rate of osteotomy and primary wound closure in patients with bisphosphonate-associated osteonecrosis of the jaw (BONJ). MATERIALS AND METHODS: Fifty patients who had received bisphosphonates intravenously and subsequently suffered from BONJ were included in the study. All patients underwent osteotomy of the affected jaw bone region and primary wound closure under general anaesthesia. They were followed up bimonthly for a period of 12 months. RESULTS: Macroscopically altered bone could be completely removed in all cases. In two patients with plasmocytoma, major bleeding occurred postoperatively that required monitoring in an intensive care unit. In two cases, recurrence of BONJ was diagnosed during the first 2 months. In three patients, recurrence appeared between the fourth and the sixth month. In these cases, an additional osteotomy had to be performed. Six patients died during the follow-up period. In the remaining 39 patients, no signs of recurrence could be detected during the follow-up of 12 months. The success rate of the surviving patients was 89% after 1 year. CONCLUSION: Due to the high success rate of osteotomy and primary wound closure, it should be checked for every patient suffering from BONJ if osteotomy is a viable treatment option.

Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study.

It was the aim of the present study to find out which radiological imaging techniques allow assessing the extent of bisphosphonate-associated osteonecrosis of the jaw (BONJ) in an adequate way. Twenty-four patients suffering from BONJ were included in the study. Before surgery, each patient was examined with panoramic radiograph, contrast-enhanced magnetic resonance imaging (MRI) and non-enhanced computed tomography. The detectability of BONJ was assessed for the three imaging techniques. The extent of the jaw region affected by BONJ was determined in MRI and CT scans and compared to the intra-operative situation. The detectability of BONJ lesions was 54% for panoramic radiographs, 92% for MRI scans and 96% for computed tomography (CT) scans. The intra-operatively assessed extent of BONJ correlated significantly with the measurements on CT scans (p = 0.0004) but did not correlate significantly with the measurements in MRI scans (p = 0.241). The intra-operatively measured extent of BONJ differed significantly from the CT measurements (p = 0.00003) but not from the MRI data (p = 0.137). Although MRI as well as CT have a high detectability for BONJ lesions that exceeds that of panoramic radiographs by far, both techniques show problems with the exact assessment of the extent of BONJ lesions in the individual patients. Therefore, the relevance of MRI and CT for the preoperative assessment of the extent of BONJ lesions is limited. Future research should focus on the identification of imaging techniques that allow assessing the extent of BONJ lesions with a higher accuracy.

Hematogenous cytokeratin 20 mRNA detection has prognostic impact in oral squamous cell carcinoma: preliminary results.

BACKGROUND: The study was designed to detect disseminated tumor cells (DTCs) in postoperative peripheral blood of patients with oral squamous cell carcinoma (OSCC) and to determine their relevance as prognostic markers by cytokeratin (CK) expression analysis. MATERIALS AND METHODS: Forty samples of peripheral blood mononuclear cells (PBMCs) isolated 4 weeks after surgery were screened for occurrence of four CK mRNA transcripts by real-time quantitative RT qPCR. Detection of mRNA expression was compared with clinicopathological parameters and disease-free survival (DFS). RESULTS: CK 17 and CK 19 could not be detected in any samples. CK 18 and CK 20 were detectable in 1 (2.5%) and in 14 (35.0%), respectively. The detection of CK 20 was not significantly associated with lymph node status, clinical stage, or differentiation grade, but was significantly higher in patients with T3 and T4 OSCC (p = 0.04). DFS was not associated with tumor size, clinical stage, or differentiation grade. But poor DFS was significantly associated with the occurrence of lymph node metastasis (p = 0.01) and detection of CK 20 (p = 0.01). CONCLUSION: DTCs in PBMCs of postoperative patients with OSCC could only be detected by determination of CK 20 mRNA. Detection of CK 20 mRNA in peripheral blood seems to be of relevance for prognosis in OSCC.

Association of polymorphisms in Tumor Necrosis Factor Alpha and Beta genes with increased risk for oral cancer.

BACKGROUND: In light of the recently found contribution of inflammation-related factors to oral oncogenesis, the possible correlation of tumor necrosis factor alpha and beta genes (TNF-alpha and TNF-beta) with risk of oral cancer was investigated. MATERIALS AND METHODS: DNA samples of 160 German and Greek patients with oral squamous cell carcinoma and 153 healthy controls of equivalent age, gender and ethnicity were studied. The functional polymorphisms TNF-alpha (-308 G/A) and TNF-beta (252 G/A), which affect gene expression, were investigated by restriction fragment length polymorphism analysis. RESULTS: The frequencies of high expression A2 (-308A) TNF-alpha allele and high expression B1 (252G) TNF-beta allele were significantly increased in cancer patients compared to controls (respectively: 62.2% versus 14.7%, p<0.0001; OR 8.65, 95% CI 5.74-13.04 and 66.9% versus 15.7%, p<0.0001; OR 10.92, 95% CI 7.4-16.2). Three combined TNF-alpha/TNF-beta genotypes (A2A2/B1B1, A1A2/B1B2, A1A2/B1B1) were over-represented in cancer patients (p<0.001). No significant differences in allele frequencies were detected among most subgroups of patients divided in regard to cancer stage, family history for cancer or thrombosis, smoking or heavy alcohol consumption habits. CONCLUSION: This study showed a strong association of TNF-alpha and TNF-beta high expression alleles with increased risk of oral cancer. These findings are in accordance with previously observed high TNF-alpha levels in serum of patients with oral cancer in comparison to healthy controls.

Influence of residual alveolar bone height on osseointegration of implants in the maxilla: a pilot study.

AIMS/BACKGROUND: For sinus floor augmentation and simultaneous implant placement, a minimum of 5 mm of residual bone height has been recommended empirically. This study was designed to test this assumption in an experimental animal trial. MATERIAL AND METHODS: In eight mini pigs, three premolars and two molars were removed on one side of the maxilla. Three months later, the animals were assigned to four groups of two animals each. A cavity was created at the base of the alveolar process so that the residual bone height was reduced to 2, 4, 6 and 8 mm, respectively. Six implants were installed and an inlay augmentation procedure was carried out using a particulated iliac bone graft. Implants were loaded with fixed provisional restorations after a healing period of 6 months. The animals were sacrificed after 6 months of functional loading. Histologic specimens were prepared and histomorphometric analysis was performed [bone-to-implant contact (BIC) ratio, interthread bone area, peri-implant bone area, crestal bone resorption (CBR)]. RESULTS: Two implants were lost during follow-up and fibrous encapsulation was detected in one additional implant. All failures occurred in one animal with a residual alveolar height of 2 mm. On the buccal aspect, BIC turned out to be significantly higher for 6 mm when compared with 2/4 mm (75.8 +/- 26.1 vs. 58 +/- 23.2/53.9 +/- 22.8; P<0.05), while on the palatal aspect, BIC was significantly higher for 6/8 mm when compared with 2/4 mm (80 +/- 17.8/78.9 +/- 10.3 vs. 55.8 +/- 26.5/55.6 +/- 21.3; P<0.05). For an alveolar height of 8 mm, CBR tended to be significantly lower than for bone heights of 2/4 mm (3.8 +/- 2.3 vs. 5.3 +/- 2.6/5.8 +/- 3.9; P<0.05). Correlation analysis revealed a significant association of BIC and interthread bone area as well as a negative association to CBR on the palatal aspect. CONCLUSION: The results of the present study show that the combination of maxillary inlay grafting and simultaneous implant placement does not hinder osseous integration even though the alveolar crest has been reduced to a residual height of 4 mm and below. However, according to histomorphometry, the highest predictability is gained in sites with residual bone heights of 6 and 8 mm.

Influence of residual alveolar bone height on implant stability in the maxilla: an experimental animal study.

AIMS/BACKGROUND: Empirically, for implant placement associated with sinus floor augmentation, a minimum of five mm of residual crestal bone height has been recommended in order to achieve sufficient initial implant stability. It has been the aim of the study to test this assumption in an experimental animal trial. MATERIAL AND METHODS: In eight mini pigs, three premolars and two molars were removed on one side of the maxilla. Three months later the animals were assigned to four groups of two animals each. A cavity was created at the base of the alveolar process so that the residual bone height was reduced to 2, 4, 6 and 8mm, respectively. The coronal part of the alveolar crest remained unchanged. An inlay augmentation procedure was carried out using a particulated autogenous bone graft from the iliac crest, and six implants (Xive, diameter 3.8mm, length 13mm) were placed. Implant stability was assessed by resonance frequency analysis at the time of implant placement (T0), after 6 months of unloaded healing (T1) and after 6 months of functional loading (T2). RESULTS: During follow-up, two implants were lost in sites with a residual alveolar bone height of 2mm. At the time of implant placement, resonance frequencies were 6754.4 +/- 268, 6500.3 +/- 281.5, 6890.3 +/- 255.4 and 7877.9 +/- 233.7 Hz for residual bone heights of 2, 4, 6 and 8mm, respectively. At stage-two surgery and after 6 months of functional loading, resonance frequencies were 6431.7 +/- 290.8, 6351.8 +/- 437.6, 6213.4 +/- 376.2 and 6826.8 +/- 458.9 Hz vs. 6171 +/- 437.4, 6047 +/- 572.4, 6156.7 +/- 272.6 and 6412.8 +/- 283.5 Hz. Statistical analysis revealed an association of residual alveolar height and implant stability at T0 and T1 only (P<0.01), while bone height was not found to influence implant survival. CONCLUSION: The results of the present trial demonstrate an association of alveolar bone height and implant stability at the time of implant placement and stage-two surgery. Yet the assumption that 5mm of residual crestal bone height is a relevant threshold for simultaneous implant placement and sinus floor augmentation is not supported from an experimental point of view.

In vitro behavior of layer-by-layer deposited molecular oligoelectrolyte films on Ti-6Al-4V surfaces.

Layer-by-layer self-assembled films of molecular oligoelectrolytes were used to modify Ti-6Al-4V surfaces in order to test their ability as potential drug delivery system. With regard to medical application the in vitro behavior of the modified material was investigated. The Ti-6Al-4V (6% aluminium, 4% vanadium) material was treated in a layer-by-layer (LbL) process with 2, 4, 6 and 8 layers of molecular oligoelectrolytes 1 and 2 and thereby doped with a fluorescent reporter molecule 2. Human osteoblasts were cultured for a period up to 5 days on the modified material. Ti-6Al-4V surfaces without modification were used as control. In order to investigate the in vitro behavior of the coating as well as the influence of components of the coating on osteoblastic cells, respectively, cell proliferation, differentiation and attachment of hFOB cells were observed by means of cell number, osteoblastic gene expression and fluorescence microscopy. Degradation behavior of the OEM (oligoelectrolyte multilayer film) was examined using optical spectroscopy. Measurement data imply that the layer-by-layer coating was successfully assembled on the Ti surface and endures steam sterilization. The fluorescence signal in cell culture medium increased strictly linear with increasing pre-assembled number of layers on the surface. Proliferation rates of the cells in experimental groups did not differ significantly from each other (P >or= 0.783). Differentiation pattern was not significantly changed by the coating. The fluorescent reporter component of the film was absorbed by osteoblastic cells and was detected by fluorescence microscopy.

Osteocutaneous free flap including medial and lateral scapular crests: technical aspects, viability, and donor site morbidity.

The aims of the present study were to check for metabolism of the bony segments of osteocutaneous free flaps that included lateral as well as medial scapular crests by 18F-fluoride positron emission tomography (PET)/computed tomography (CT) examinations and to assess donor site morbidity. Twenty patients were included in the study. In 10 patients, osteocutaneous free flaps were harvested that included lateral as well as medial scapular crests. Seven days after surgery, an 18F-fluoride PET/CT examination was performed to assess the metabolism and viability of the bony segments. In the additional 10 patients, flaps were harvested that only included the lateral scapular crest. All patients were asked to fill in the disabilities of the arm, shoulder, and hand (DASH) questionnaire 1 and 6 months after surgery. In the 10 free flaps that included lateral as well as medial scapular crests, 18F-fluoride PET/CT examinations revealed metabolism and viability of both bony segments. The DASH scores for the two patient groups did not differ significantly at 1 and 6 months after surgery (p(1 month) = 0.520, p(6 months) = 0.545). It seems that scapular osteocutaneous free flaps adopting lateral as well as medial scapular crests are a viable option for mandibular reconstruction and may be an alternative to the fibular double barrel.

Expression of MAGE-A12 in oral squamous cell carcinoma.

Melanoma associated-A antigens (MAGE-A) are silent in normal tissues except testis. However, they are activated ina variety of different tumors. Thus, their expression is highly specific to cancer cells. Reverse transcription-nested polymerase chain reaction (RT-nPCR) is a highly sensitive technique that has been used successfully for the detection of MAGE genes in tissue samples. The aim of the study is to analyze the expression rate of MAGE-A12 in oral squamous cell carcinoma (OSCC) using a high sensitive RT-nPCR. Total of 57 tissue samples obtained from patients with OSCC and 20 normal oral mucosal (NOM) probes of otherwise healthy volunteers were included to this study. No expression of MAGE-A12 was observed in the non-neoplasticNOM tissues. MAGE-A12 was expressed in 49.1% of the investigated tumor samples. The correlation between malignant lesion and MAGE-A12 detection was significant (p<0.001). It is concluded that results of this study may indicate MAGE-A12 asa useful additional diagnostic marker especially for the early detection of OSCC distinguishing neoplastic transformation and detection of occult and/or rare disseminated cancer cells. In addition, MAGE-A12 expression in OSCC may also determine anew immunotherapeutic target and might be warranted to develop vaccine for OSCC

Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma.

PURPOSE: Determination of marker for identification of oral squamous cell carcinoma (OSCC) is important for early diagnosis and individual therapy. Cytokeratins (CKs) like CK 19 and CK 20 are known to be useful diagnostic and prognostic markers for solid tumors. The aim of this study was to evaluate the relevance of further CKs for diagnosis of OSCC. MATERIALS: In 10 OSCC and 5 normal mucosal samples, the expression patterns of 31 CK genes were examined by cDNA microarray in order to identify CKs with most pronounced over-expression. The results were verified for CK 17, CK 19, and CK 20 in addition to 46 OSCC samples by relative quantification (RQ) using SYBR green real-time reverse transcriptase polymerase chain reaction (RT qPCR). A correlation of the CK expressions with the tumor classification was carried out. RESULTS: cDNA microarray analyses showed that out of all CKs, CK 17 was up-regulated strongest in OSCC compared to normal samples, and over-expression was most significantly associated with diagnosis (P = 0.002). Expression rates of CK 19 and CK 20 were not significantly different between OSCC samples and normal samples. In 56 samples analyzed by real-time RT qPCR, CK 17 was over-expressed in 53 (94.6%), CK 19 in 18 (32.1%), and CK 20 in 7 (12.5%). The over-expression of CK 17 was significantly associated with metastases of neck lymph nodes (P < 0.05). CK 19 was significantly over-expressed in T3 and T4 OSCC, in stage III and IV patients (P < 0.05), and in poorly differentiated OSCC (P < 0.03). The over-expression of CK 20 was significantly associated with metastases of neck lymph nodes (P < 0.03). Determined by RQ, the mean value of CK 17 over-expression was significantly higher than that of the other CKs (P < 0.01), and was significantly associated with T1 and T2 OSCC (P < 0.03) and with stage I and II patients (P < 0.01). CONCLUSION: CK 19 might be linked to the clinical progression and differentiation of OSCC, and CK 20 could be associated with metastases of neck lymph nodes in OSCC. Due to the significant up-regulation and the strong over-expression, CK 17 might be the most suitable marker for diagnosis of OSCC out of the CK-family.

Prevalence of HPV types in a cohort of Greeks with clinical indication of infection.

BACKGROUND: Several types of human papilloma virus (HPV) have been associated with increased risk for epithelial malignancies. In light of a recently available vaccine that protects against persistent infection by certain HPV types (6, 11, 16, 18) and resulting neoplasias, the prevalence of HPV types was investigated in a cohort of people with a suspected viral infection. PATIENTS AND METHODS: The studied material consisted of genital or oral scrapings obtained from 263 consecutively referred Greeks (aged 18-64 years) with a clinical indication of HPV infection. DNA samples isolated from scrapings were tested by PCR, using consensus primers for at least 50 HPV types. In cases of detected viral DNA sequence, HPV typing was performed by restriction analysis using 4 enzymes and confirmed by DNA sequencing. RESULTS: 215/263 (81.7%) of the samples were HPV-positive. HPV types associated with high risk for neoplasias were detected in 91/215 (423%), intermediate risk types in 64/215 (29.8%) and low-risk types in 60/215 (27.9%) of the positive samples. A total of 85/215 (39.5%) were positive for one of the vaccine-related types. Furthermore, types 16 and 18 comprised about the same proportion of the high-risk types detected in this study (35/91, 385%). CONCLUSION: The observed high prevalence rate of high-risk types underlines the importance of testing individuals with an indication of a possible HPV infection. In addition, there is a need for prevention strategies, such as the annual Pap smear screening of women, as well as wider use of HPV molecular screening and vaccines targeted at common HPV types.

Metastases following biopsy of oral carcinoma in hamsters and the role of local prebiopsy bleomycin.

BACKGROUND: This animal study researches the effect of biopsy on metastasis of oral carcinoma. MATERIALS AND METHODS: Sixty hamsters developed oral tumors after treatment with 9,10-dimethyl-1,2-benzanthracene and were then divided into six groups. Animals of groups 1 and 2 did not receive any treatment, while groups 3-6 were biopsied at the end of the 14th week and groups 5 and 6 also received a prebiopsy intratumoral injection of bleomycin. Animals of groups 1, 3, 5 and 2, 4, 6 were sacrificed at the 17th and 19th week respectively. Specimens of tumors, ipsilateral cervical lymph nodes, lungs and livers were obtained from all animals and histologically examined. RESULTS: All animals developed oral squamous cell carcinomas. In group 4, four out of ten animals showed metastases to the cervical lymph nodes, and one out of four showed a distant metastasis to the lung. CONCLUSION: Delay of treatment following biopsy can increase the risk of cervical lymph node metastases which can be reduced by an intratumoral administration of bleomycin.

A DNA polymorphism of stromal-derived factor-1 is associated with advanced stages of oral cancer.

BACKGROUND: Stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies, but not with oral squamous cell carcinoma. In light of the known contribution to the development of oral cancer of other gene polymorphisms for proteins responsible for angiogenesis, inflammation and thrombosis, this study investigated whether the G801A polymorphism in the SDF-1 gene is associated with this malignancy. PATIENTS AND METHODS: The G801A polymorphism was examined by restriction fragment length polymorphism analysis in DNA samples from 159 patients with oral squamous cell carcinoma and 101 matched healthy controls. RESULTS: The detected allele frequency of the "high production related" A allele in the control group was 25.3%. There was a slight decrease in allele frequency in patients (18.6%), but it was not statistically significant. The same pattern was observed in subgroups of patients in regard to smoking habits and family history of cancer or thrombosis. Interestingly, in comparison to controls, the A allele frequency was significantly lower in patients with advanced cancer stages III and IV (12.5%, p=0.005) and in patients with alcohol abuse (12.5%, p=0.02). CONCLUSION: The G801A polymorphism of the SDF-1 gene is associated with advanced stages of oral cancer, especially in alcohol abusers.

The interleukin-10 (-1082A/G) polymorphism is strongly associated with increased risk for oral squamous cell carcinoma.

BACKGROUND: Increased levels of interleukin-10 (IL-10) have been observed in patients with oral cancer, possibly as a result of suppression of the immune response. Based on this, the -1082A/G polymorphism, which influences IL-10 gene expression level, was investigated in regard to its possible association with risk for oral cancer. PATIENTS AND METHODS: The polymorphism was examined in DNA samples of 144 patients with oral squamous cell carcinoma and 141 healthy controls of equivalent gender, age and ethnicity. RESULTS: The detected allele frequencies for the high expression G allele were significantly higher in patients compared to controls (34.7% versus 21.3%, respectively, p=0.0004), as well as in patients that were smokers but not those that were heavy alcohol consumers. This highly significant difference in G allele frequency was mainly due to the increase of AG heterozygotes in patients compared to controls (OR 3.05, 95% CI 1.84-5.05). CONCLUSION: These findings suggest that the high expression G allele of the -1082A/G polymorphism of the inflammation and angiogenesis-related IL-10 is strongly associated with increased risk for oral cancer.

Angiotensinogen polymorphism is associated with risk for malignancy but not for oral cancer.

BACKGROUND: In light of the recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of the angiotensinogen gene (AGT) with increased risk of oral cancer. MATERIALS AND METHODS: The M235T polymorphism, which influences AGT gene expression, was evaluated by restriction fragment length polymorphism analysis in the DNA samples of 163 German and Greek patients with oral squamous cell carcinoma (OSCC) and 124 healthy controls of equivalent gender, ethnicity and age. RESULTS: No significant difference of the mutant (235T) allele, which results in higher AGT gene expression, was observed in the whole patient group in comparison with the normal controls. Similarly, compared to the controls no significant difference of either allele or carrier frequency was detected in almost every subgroup of patients. Only in the subgroup of patients with a positive family history of cancer was a significant increase of mutant T allele and carrier frequencies observed, compared to the controls (50% vs. 36.7% and 79.3% vs. 61.3%, respectively, p < 0.05 in both cases). In this particular subgroup of patients the odds ratio for OSCC of TT homozygotes was 3.57 (CI 95% 1.2-10.62), while for the MT heterozygotes it was 2.41 (CI 95% 1.06-5.49). CONCLUSION: This study did not reveal an association of the AGT M235T polymorphism with oral oncogenesis, but certainly suggested a possible association of this specific polymorphism with other types of cancer. The present findings support a previous suggestion that the pathway of oral oncogenesis is probably based on angiotensin-converting enzyme and bradykinin interaction and not on AGT and angiotensin peptides.

Expression of melanoma-associated antigens in oral squamous cell carcinoma.

BACKGROUND: Melanoma-associated antigens-A (MAGE-A) are expressed in a variety of tumors but not in normal tissues. Thus, their detection is highly specific to cancer cells, which makes them potential targets for the diagnosis, prognosis and also immunotherapy of neoplastic diseases. METHODS: To determine the expression pattern and potential role of MAGE-A antigens in oral squamous cell carcinoma (OSCC), expression patterns of MAGE-A1-A6 and A12 were analyzed in 55 OSCC and 20 healthy oral mucosa using high-sensitive reverse transcription-nested polymerase chain reaction (RT-nPCR). RESULTS: The 85.45% of tumor specimens expressed at least one of these genes. A significant correlation between the expression of MAGE-A1-A6 and A12 and malignancy was ascertained (P = 0.0001). On the contrary, none of the normal mucosal specimens expressed one of the MAGE-A subtypes. Antigen expression did not correlate with clinicopathological parameters, such as TNM classification, grading and clinical stage of OSCC. CONCLUSIONS: Multiple simultaneous detection of MAGE-A1-A6 and A12 expression has been found to be more specific and sensitive than the detection of single MAGE-A antigen for the diagnostic and prognostic evaluation of OSCC. In addition, monitoring the expression of several MAGE-A subtypes may determine suitable immunotherapeutic targets. Subsequently, coexpressed genes may be warranted for developing polyvalent vaccines.

HPV detection rate in saliva may depend on the immune system efficiency.

BACKGROUND: Human papilloma virus (HPV) has been established as a major etiological factor of anogenital cancer. In addition, HPV has also been implicated in oral carcinogenesis but its detection rates appear to be highly variable, depending on the patient population tested, the molecular methodology used, as well as the type of oral specimen investigated. For example, saliva is an oral fluid that may play a role in HPV transmission, although the detection rates of the virus are lower than tissue. Recent evidence has indicated that HPV-related pathology is increased in the oral cavity of human immunodeficiency virus (HIV)-positive individuals. In order to investigate whether the presence of different HPV types in saliva depends on immune system efficiency, oral fluid samples of patients with oral cancer and without any known immune deficiency were compared with those of HIV-positive individuals. PATIENTS AND METHODS: Saliva samples were collected from 68 patients with oral squamous cell carcinoma and 34 HIV seropositive individuals. HPV DNA sequences were detected by L1 concensus polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) analysis and DNA sequencing for HPV typing. RESULTS: HPV DNA was detected in 7/68 (10.3%) of the oral cancer patients and in 12/34 (35.3%) of the HIV-positive individuals, a highly significant difference (p = 0.006; odds ratio 4.753; 95% confidence interval 1.698-13.271). Among HPV-positive samples, the prevalence of HPV types associated with high oncogenic risk was similar in oral cancer and HIV-positive cases (71.4% and 66.7%, respectively). In both groups, the most common HPV type was high-risk 16 (50% and 42.8%, respectively). CONCLUSION: Although a similar pattern of HPV high-risk types was detected in oral cancer and HIV-positive cases, the quantitative detection of HPV in saliva significantly depended on immune system efficiency. Furthermore, the significantly increased detection rates of HPV in saliva of HIV-positive individuals may be associated with high risk for development of HPV-related oral lesions, including malignancy.

H-ras and c-fos exhibit similar expression patterns during most stages of oral oncogenesis.

BACKGROUND: H-ras and c-fos oncogenes interact in signalling pathways but their level and time course of expression during oral cancer development are unclear. The present study used an animal model for the simultaneous investigation of H-Ras and c-Fos expression in sequential stages of oral oncogenesis. MATERIALS AND METHODS: Three experimental groups of Syrian golden hamsters (A, B and C; 10 animals each) and one control group (7 animals) were used. The buccal pouches of hamsters in groups A, B and C were treated with 0.5% of the carcinogen 9,10-dimethyl-1,2-benzanthracene and were excised at 10, 14 and 19 weeks, respectively. The biopsies, which included tissue stages ranging from normal oral mucosa to moderately differentiated carcinoma, were studied immunohistochemically. RESULTS: A reduction in both H-Ras and c-Fos expression was observed from group A to B and from hyperplasias to early tumour stages, while a simultaneous increase was noted from group B to C and from well-differentiated to moderately-differentiated carcinomas. The H-ras/c-fos expression ratio had a value of approximately (1.09 +/- 0.21) in five out of seven studied tissue stages. CONCLUSION: H-Ras and c-Fos exhibit a similar expression pattern throughout most stages of oral carcinogenesis, an observation supported by the known molecular pathway connecting H-ras signalling with subsequent c-fos gene transcription.