Prospective manipulation of the gut microbiome with microbial ecosystem therapeutic 4 (MET4) in HPV-related locoregionally-advanced oropharyngeal cancer squamous cell carcinoma (LA-OPSCC) undergoing primary chemoradiation: ROMA2 study.

BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation. METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis. RESULTS: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics. CONCLUSIONS: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.

The microbiome of HPV-positive tonsil squamous cell carcinoma and neck metastasis.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) has now surpassed cervical cancer as the most common site of HPV-related cancer in the United States. HPV-positive OPSCCs behave differently from HPV-negative tumors and often present with early lymph node involvement. The bacterial microbiome of HPV-associated OPSCC may contribute to carcinogenesis, and certain bacteria may influence the spread of cancer from the primary site to regional lymphatics. OBJECTIVE: To determine the bacterial microbiome in patients with HPV-associated, early tonsil SCC and compare them to benign tonsil specimens. METHOD: The microbiome of primary tumor specimens and lymph nodes was compared to benign tonsillectomy specimens with pan-pathogen microarray (PathoChip). RESULTS: A total of 114 patients were enrolled in the study. Patients with OPSCC had a microbiome that shifted towards more gram-negative. Numerous signatures of bacterial family and species were associated with the primary tumors and lymph nodes of cancer patients, including the urogenital pathogens Proteus mirabilis and Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, and Orientia tsutsugamushi. CONCLUSION: Our results suggest that detection of urogenital pathogens is associated with lymph node metastasis for patients with HPV-positive OPSCCs. Additional studies are necessary to determine the effects of the OPSCC microbiome on disease progression and clinical outcomes.

Oral microbiota and vitamin D impact on oropharyngeal squamous cell carcinogenesis: a narrative literature review.

An emerging body of research is revealing the microbiota pivotal involvement in determining the health or disease state of several human niches, and that of vitamin D also in extra-skeletal regions. Nevertheless, much of the oral microbiota and vitamin D reciprocal impact in oropharyngeal squamous cell carcinogenesis (OPSCC) is still mostly unknown. On this premise, starting from an in-depth scientific bibliographic analysis, this narrative literature review aims to show a detailed view of the state of the art on their contribution in the pathogenesis of this cancer type. Significant differences in the oral microbiota species quantity and quality have been detected in OPSCC-affected patients; in particular, mainly high-risk human papillomaviruses (HR-HPVs), Fusobacterium nucleatum, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Candida spp. seem to be highly represented. Vitamin D prevents and fights infections promoted by the above identified pathogens, thus confirming its homeostatic function on the microbiota balance. However, its antimicrobial and antitumoral actions, well-described for the gut, have not been fully documented for the oropharynx yet. Deeper investigations of the mechanisms that link vitamin D levels, oral microbial diversity and inflammatory processes will lead to a better definition of OPSCC risk factors for the optimization of specific prevention and treatment strategies.

Role of the oral microbiota in cancer evolution and progression.

Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial roles in the health status of individuals. Epidemiological studies related to molecular pathology have revealed that there is a close relationship between oral microbiota and tumor occurrence. Oral microbiota has attracted considerable attention for its role in in-situ or distant tumor progression. Anaerobic oral bacteria with potential pathogenic abilities, especially Fusobacterium nucleatum and Porphyromonas gingivalis, are well studied and have close relationships with various types of carcinomas. Some aerobic bacteria such as Parvimonas are also linked to tumorigenesis. Moreover, human papillomavirus, oral fungi, and parasites are closely associated with oropharyngeal carcinoma. Microbial dysbiosis, colonization, and translocation of oral microbiota are necessary for implementation of carcinogenic functions. Various underlying mechanisms of oral microbiota-induced carcinogenesis have been reported including excessive inflammatory reaction, immunosuppression of host, promotion of malignant transformation, antiapoptotic activity, and secretion of carcinogens. In this review, we have systemically described the impact of oral microbial abnormalities on carcinogenesis and the future directions in this field for bringing in new ideas for effective prevention of tumors.

Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients.

PURPOSE: The present retrospective multicenter study intended to investigate the factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas. METHODS: A total of 326 patients who underwent radiotherapy for oral and oropharyngeal cancers were enrolled in the study. The patients' age, sex, body mass index, primary site, diabetes, serum albumin, creatinine, hemoglobin, leukocyte and lymphocyte, concurrent cisplatin or cetuximab, method of radiation, total radiation dose, feeding route, use of spacers, pilocarpine hydrochloride, and corticosteroid ointment were examined, and the associations of each variable with oral mucositis and candidiasis were analyzed by multivariate Cox regression analysis. RESULTS: Grade 3 oral mucositis occurred in 136 (41.7%) patients. Male sex, oropharyngeal cancer, low hemoglobin levels, low leukocytes or lymphocytes, concurrent cisplatin or cetuximab, and oral feeding were found to be significantly associated with a higher incidence of severe oral mucositis. Oral candidiasis occurred in 101 (31.0%) patients. Oropharyngeal cancer, low leukocyte count, and oral mucositis of grade 2 or higher were found to be significantly associated with a higher incidence of oral candidiasis. The use of a topical steroid ointment was not found to be a risk factor for oral candidiasis. CONCLUSIONS: The present retrospective study demonstrated that certain factors may predispose patients with oral and oropharyngeal cancers receiving radiotherapy to develop severe oral mucositis and oral candidiasis. A preventive strategy for severe oral mucositis needs to be established in the future for high-risk cases.

Alterations of salivary microbial community associated with oropharyngeal and hypopharyngeal squamous cell carcinoma patients.

The highest number (35.1% of global incident cases) of new oropharyngeal (OP) and hypopharyngeal (HP) cancer cases was reported in South-Central Asia. The highest incidence of HP cancer in India was reported in East Khasi Hills District of Meghalaya, Aizawl District of Mizoram, and Kamrup Urban District of Assam. HP and OP cancer showed the highest mortality rate, worst prognoses and the highest rate of nodal metastases and distant metastases. Thus, research is required to detect specific biomarkers for early prevention and diagnosis for these cancers. Oral microbiome signatures in saliva are considered as a potential diagnostic biomarker for OP and HP cancer. Bacterial profile alterations in OP and HP cancer have not been reported in India population, to establish the association of oral bacteria in the progression of OP and HP cancer; we studied bacterial communities in saliva of eight OP and seven HP cancer patients as compared to healthy controls using 16S rRNA V3-V4 region sequencing. The higher abundance of Haemophilus parainfluenzae, Haemophilus influenzae and Prevotella copri and lower abundance of Rothia mucilaginosa, Aggregatibacter segnis, Veillonella dispar, Prevotella nanceiensis, Rothia aeria, Capnocytophaga ochracea, Neisseria bacilliformis, Prevotella nigrescens and Selenomonas noxia in saliva of OP and HP cancer patients may be considered as a non-invasive diagnostic biomarker for OP and HP cancer patients. Streptococcus anginosus may be considered as a non-invasive diagnostic biomarker for OP cancer patients only. Therefore, evaluation of salivary microbial biomarkers may be informative to understand the pathobiology and carcinogenesis of OP and HP cancer.

Culture-independent studies on bacterial dysbiosis in oral and oropharyngeal squamous cell carcinoma: A systematic review.

Imbalance within the resident bacterial community (dysbiosis), rather than the presence and activity of a single organism, has been proposed to be associated with, and to influence, the development and progression of various diseases; however, the existence and significance of dysbiosis in oral/oropharyngeal cancer is yet to be clearly established. A systematic search (conducted on 25/01/2018 and updated on 25/05/2018) was performed on three databases (Pubmed, Web of Science & Scopus) to identify studies employing culture-independent methods which investigated the bacterial community in oral/oropharyngeal cancer patients compared to control subjects. Of the 1546 texts screened, only fifteen publications met the pre-determined selection criteria. Data extracted from 731 cases and 809 controls overall, could not identify consistent enrichment of any particular taxon in oral/oropharyngeal cancers, although common taxa could be identified between studies. Six studies reported the enrichment of Fusobacteria in cancer at different taxonomic levels whereas four studies reported an increase in Parvimonas. Changes in microbial diversity remained inconclusive, with four studies showing a higher diversity in controls, three studies showing a higher diversity in tumors and three additional studies showing no difference between tumors and controls. Even though most studies identified a component of dysbiosis in oral/oropharyngeal cancer, methodological and analytical variations prevented a standardized summary, which highlights the necessity for studies of superior quality and magnitude employing standardized methodology and reporting. Indeed an holistic metagenomic approach is likely to be more meaningful, as is understanding of the overall metabolome, rather than a mere enumeration of the organisms present.

Survival impact of treatment delays in surgically managed oropharyngeal cancer and the role of human papillomavirus status.

BACKGROUND: The impact of treatment delays on survival in oropharyngeal cancer and whether the effect varies by human papillomavirus (HPV) status have yet to be defined. METHODS: Retrospective analysis of the survival impact of time from diagnosis to surgery (DTS), surgery to radiation (SRT), and duration of radiation (RTD) for patients in the National Cancer Database with resected oropharyngeal cancer who underwent adjuvant radiation from 2010 to 2014. RESULTS: We identified optimal thresholds of 30, 40, and 51 days for DTS, SRT, and RTD, respectively, with treatment times exceeding these thresholds associated with significantly worse overall survival. Prolonged SRT and RTD were associated with mortality regardless of HPV status, although rising DTS was only predictive among patients with HPV-negative tumors. CONCLUSIONS: Treatment delays significantly impact survival in oropharyngeal cancer. The consequences of prolonged DTS may be stronger in HPV-negative than HPV-positive disease. These data serve as a foundation for future research and clinical management.

Human papillomavirus-associated oropharyngeal cancer among patients aged 70 and older: Dramatically increased prevalence and clinical implications.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence among older adults. However, the role of human papillomavirus (HPV) in driving this trend and its prognostic significance in this population have not been established. METHODS: The National Cancer Database was queried for patients with OPSCC diagnosed from 2010 to 2015 undergoing either surgery or radiotherapy (RT) with known HPV status. Older adults were defined as those aged 70 years or older. RESULTS: Among 43,427 OPSCC patients, the proportion of HPV-positive OPSCC increased from 45.1% to 63.3% in older adults (P < 0.001). In 19,358 patients meeting the inclusion criteria for survival analyses, HPV positivity was associated with improved survival for older adults undergoing either definitive RT (hazard ratio [HR] = 0.63, 95% confidence interval [CI] 0.55-0.72, P < 0.001) or surgery (HR = 0.37, 95% CI 0.25-0.53, P < 0.001) in multivariable analysis. In propensity score-matched cohorts, 3-year overall survival was 69.1% versus 55.5% (P < 0.001) in older adults with HPV-positive and HPV-negative OPSCC undergoing definitive RT, respectively, and 88.5% versus 69.1% (P = 0.001) for older adults undergoing surgery. Although HPV positivity was associated with improved survival among all age groups receiving RT, the magnitude of the effect diminished with increasing age (interaction P < 0.001). No interaction between age and the impact of HPV status on survival was seen for surgical patients (interaction P = 0.72). CONCLUSIONS: The epidemiologic landscape of HPV-positive OPSCC is evolving, with a dramatic increase in the proportion of HPV-associated OPSCC among patients 70 years or older. HPV remains a powerful predictor of improved survival in elderly patients, but with less pronounced effect on older adults undergoing definitive RT.

The Performance of an Oral Microbiome Biomarker Panel in Predicting Oral Cavity and Oropharyngeal Cancers.

The oral microbiome can play a role in the instigation and progression of oral diseases that can manifest into other systemic conditions. These associations encourage the exploration of oral dysbiosis leading to the pathogenesis of cancers. In this study, oral rinse was used to characterize the oral microbiome fluctuation associated with oral cavity cancer (OCC) and oropharyngeal cancers (OPC). The study cohort consists of normal healthy controls (n = 10, between 20 and 30 years of age; n = 10, above 50 years of age), high-risk individuals (n = 11, above 50 years of age with bad oral hygiene and/or oral diseases) and OCC and OPC patients (n = 31, HPV-positive; n = 21, HPV-negative). Oral rinse samples were analyzed using 16S rRNA gene amplicon sequencing on the MiSeq platform. Kruskal-Wallis rank test was used to identify genera associated with OCC and OPC. A logistic regression analysis was carried out to determine the performance of these genera as a biomarker panel to predict OCC and OPC. In addition, a two-fold cross-validation with a bootstrap procedure was carried out in R to investigate how well the panel would perform in an emulated clinical scenario. Our data indicate that the oral microbiome is able to predict the presence of OCC and OPC with sensitivity and specificity of 100 and 90%, respectively. With further validation, the panel could potentially be implemented into clinical diagnostic and prognostic workflows for OCC and OPC.

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma.

BACKGROUND: An opportunistic oral pathogen, Treponema denticola (Td), has been linked to orodigestive carcinogenesis, but its role in oropharyngeal squamous cell carcinoma (OPSCC) has remained open. We evaluated the presence of Td chymotrypsin-like protease (Td-CTLP) in a series of 201 unselected consecutive OPSCC patients, and the relation of the Td-CTLP to human papillomavirus (HPV) status, to expression of toll-like receptors (TLR) 5, 7, and 9, and to clinical parameters and patient outcome. METHODS: Clinicopathological data came from hospital registries. The expression of cell surface-bound Td-CTLP was evaluated by immunohistochemistry. Immunoexpression of TLRs 5, 7, and 9, and HPV status we studied earlier in this patient series. RESULTS: We detected Td-CTLP in 81% of the OPSCC, and especially in HPV-negative tumours (48% of all OPSCCs). Among the HPV-positive tumours (52% of all OPSCCs), low Td-CTLP expression associated with low TLR 5 and high TLR 7 expression. Among those HPV-negative, higher TLR 5 and lower TLR 7 expression associated with high Td-CTLP expression. Strong Td-CTLP expression associated with poor disease-specific survival, but no similar association among HPV-positive and HPV-negative subgroups emerged. CONCLUSIONS: Td-CTLP was highly expressed in OPSCC and was associated with the HPV status of tumour tissue.

Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer.

Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor oral hygiene are established risk factors. To date, no large-scale case-control studies have considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with oral cancer. We compared the composition, diversity, and function of the oral microbiomes of 121 oral cancer patients to 242 age- and gender-matched controls using a metagenomic multivariate analysis pipeline. Significant shifts in composition and function of the oral microbiome were observed with poor oral hygiene, tobacco smoking, and oral cancer. Specifically, we observed dramatically altered community composition and function after tooth loss, with smaller alterations in current tobacco smokers, increased production of antioxidants in individuals with periodontitis, and significantly decreased glutamate metabolism metal transport in oral cancer patients. Although the alterations in the oral microbiome of oral cancer patients were significant, they were of substantially lower effect size relative to microbiome shifts after tooth loss. Alterations following tooth loss, itself a major risk factor for oral cancer, are likely a result of severe ecological disruption due to habitat loss but may also contribute to the development of the disease.

The salivary microbiome as an indicator of carcinogenesis in patients with oropharyngeal squamous cell carcinoma: A pilot study.

This study aimed to undertake an initial, comparative analysis of the oral salivary microbiome of patients with oral and oropharyngeal squamous cell carcinoma versus healthy controls. This project, conceived as a pilot study, included 11 patients (1 female, 10 male, mean age 61.6 yrs., SD = 8.2 yrs.) and 11 healthy controls (1 female, 10 male, mean age 46.7 yrs., SD = 15.1 yrs.). Samples of saliva were analysed by high-throughput sequencing of the 16S rRNA gene using the MiSeq platform. Sequence data revealed microbial changes that may mirror disease progression and reflect clinical preconditions such as age, alcohol consumption, tumour size, lymph node status, smoking habit, and tumour HPV-positivity. Consequently, mapping microbial changes in patients with oral and oropharyngeal squamous cell carcinomas might improve our understanding of the pathobiology of the disease, and help in the design of novel diagnostic and treatment strategies.

Human papillomavirus and oropharyngeal cancer in Greenland in 1994-2010.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is associated with the sexually transmitted human papillomavirus (HPV), smoking and alcohol. In Greenland, a high rate of HPV-induced cervical cancer and venereal diseases are found, which exposes the population for high risk of HPV infection. In Greenland, only girls are included in the mandatory HPV vaccination program. OBJECTIVE: To investigate the annual incidence of OPSCC and the proportion of HPV-associated OPSCC (HPV+ OPSCC) in Greenland in 1994-2010. DESIGN: At Rigshospitalet, University of Copenhagen, we identified all Greenlandic patients diagnosed and treated for OPSCC from 1994 to 2010. Sections were cut from the patient's paraffin-embedded tissue blocks and investigated for p16 expression by immunohistochemistry. HPV analyses were performed with 2 sets of general HPV primers and 1 set of HPV16-specific primer. HPV+ OPSCC was defined as both >75% p16+ cells and PCR positive for HPV. RESULTS: Of 26 Greenlandic patients diagnosed with OPSCC, 17 were males and 9 were females. The proportion of HPV+ OPSCC in the total study period was 22%, without significant changes in the population in Greenland. We found an increase in the proportion of HPV+ OPSCC from 14% in 1994-2001 to 25% in 2002-2010 (p=0.51). Among males from 20 to 27% (p=0.63) and in females from 0 to 20% (p=0.71). The annual OPSCC incidence increased from 2.3/100,000 (CI=1.2-4.2) in 1994-2001 to 3.8/100,000 (CI=2.4-6.2) in 2002-2010: among males from 2.4/100,000 (CI=1.0-5.7) to 5.0/100,000 (CI=2.9-8.9). CONCLUSION: Even though the population is at high risk of HPV infection, the proportion of 22% HPV+ OPSCC in the total study period is low compared to Europe and the United States. This might be explained by our small study size and/or by ethnic, geographical, sexual and cultural differences. Continuing observations of the OPSCC incidence and the proportion of HPV+ OPSCC in Greenland are needed.

Detection of human papillomavirus using hybrid capture 2 in oral brushings from patients with oropharyngeal squamous cell carcinoma.

Detection of high-risk (HR) human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SCC) has important prognostic implications; patients exhibit improved survival compared with patients with HPV- SCC. Oral brushing and rinsing samples were obtained from patients with oropharyngeal, oral cavity, or hypopharyngeal SCC and tested for HR-HPV using Hybrid Capture 2 (HC2; QIAGEN, Valencia, CA). HR-HPV in situ hybridization (ISH) was performed on biopsy tissue samples from the same patients. Oral cytologic samples from 16 SCCs were tested by HC2. Biopsy tissue samples were available for ISH in 11 cases. Five oropharyngeal SCCs were HR-HPV+ by ISH and HC2 (oral brushing). Of the oropharyngeal SCCs, 2 were positive by HC2 (oral brushing) and negative or equivocal by ISH. We found that 2 oral cavity carcinomas and 2 hypopharyngeal carcinomas were negative by HC2. One hypopharyngeal cancer was positive by ISH. All oral rinsing samples were negative by HC2. HC2 may be an effective method of determining HR-HPV status in patients with oropharyngeal SCC.

Helicobacter pylori in tonsillar and adenoid tissue and its possible role in oropharyngeal carcinogenesis.

Helicobacter pylori is a well-known gastric pathogen. It plays a major role in the pathogenesis of chronic gastritis, duodenal and gastric ulcers, adenocarcinoma and gastric lymphoma. HP infection is one of the most common bacterial infections worldwide. Recently, the oral cavity was proposed as an extragastric reservoir of HP infection. HP was detected by culture and PCR in both dental plaque and saliva. It is supposed that HP infection can cause the same immunological changes in the oropharyngeal mucosa as in gastric mucosa and can also contribute to the progression of oropharyngeal diseases. HP can induce production of different cytokines and regulatory molecules, which are suggested to play a role in carcinogenesis of the oropharynx. Only a few studies have explored the presence of HP in tonsillar and adenoid tissue, where MALT is present similar to the gastric mucosa. The results of these studies were inconsistent. The question of persistence of HP in tonsillar and adenoid tissue and its role in the pathogenesis of oropharyngeal diseases still remains unclear. In this review, recent findings about oral HP are considered. Possibilities of diagnostics of HP in oral specimens are discussed.

Helicobacter pylori, chronic atrophic gastritis, inactive aldehyde dehydrogenase-2, macrocytosis and multiple upper aerodigestive tract cancers and the risk for gastric cancer in alcoholic Japanese men.

BACKGROUND: Gastric carcinoma occurs at a high rate in alcoholic Japanese men. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/2*2) and macrocytosis (mean corpuscular volume [MCV] > or = 106 fl) enhance the risk for esophageal carcinoma, which frequently occurs with gastric carcinoma in this population. Whether alcoholism affects Helicobacter pylori-induced chronic atrophic gastritis (CAG) is unknown. METHODS: This study of Japanese alcoholic men with (n = 45) and without (n = 281) gastric carcinoma included assessment of H. pylori IgG antibody, serum pepsinogen-confirmed CAG, MCV, and ALDH2 genotype. RESULTS: The gastric carcinoma cases had a significantly higher age-adjusted prevalence of H. pylori-positivity (78%vs 57%), CAG (78%vs 42%), ALDH2*1/2*2 (36%vs 14%), MCV > or =106 fl (38%vs 20%), and concurrent esophageal/oropharyngolaryngeal carcinoma (18%vs 5%) than controls. Among gastric cancer-free controls, the prevalence of CAG was higher than generally reported in Japan, regardless of H. pylori status (H. pylori-positive, 56%vs 35-36% for Japanese general population; H. pylori-negative, 8%vs 1-3%). Alcoholism may accelerate the progression of CAG. Each of these factors increased the risk of gastric carcinoma (OR(s) = 3.7 for H. pylori-positive, 2.7 for non-severe CAG, 8.7 for severe CAG, 3.5 for ALDH2*1/2*2, 2.5 for MCV > or =106 fl, and 3.7 for concurrent carcinoma). A multivariate analysis showed that CAG and ALDH2*1/2*2 were independently related to the risk of gastric carcinoma. Combinations of CAG and ALDH2*1/2*2 showed greater risks of gastric carcinoma (OR(s) = 4.0 for non-severe CAG alone, 17.6 for severe CAG alone, 9.7 for ALDH2*1/2*2 alone, 17.1 for non-severe CAG plus ALDH2*1/2*2, and 39.2 for severe CAG plus ALDH2*1/2*2). CONCLUSIONS: Combining blood tests for H. pylori, CAG, MCV and ALDH2 genotype could offer a new means of predicting risk of gastric carcinoma in Japanese alcoholic men.

The influence of oral hygiene on salivary quality in the Ames Test, as a marker for genotoxic effects.

Squamous cell carcinomas of the upper aerodigestive tract are a global health-political challenge. Accordingly, current research efforts are aimed towards the opportunities for early recognition of risk patients, and at the recognition of risk factors related to carcinogenesis. We determined the revertant number of the variety Salmonella typhimurium TA 98 and TA 100 after incubation, with saliva samples from 100 probands as a measure of a genotoxic environment within the oral cavity, depending on the dental status as measure of oral health. Beside chronic alcohol (p=0.032) and tobacco consumption (p<0.001), the dental status displayed in partial aspects (high plaque index, high number of decayed teeth, prosthetically not rehabilitated status, p or= 0.104). Therefore, it can be concluded that the polymicrobial supragingival plaque, as a possible independent factor, possesses a relevant mutagenic interaction with saliva, and that individual oral health is a co-factor in the development of carcinomas in the oral cavity.

[Streptococcus milleri. An early sign of cancer in otorhinolaryngologic patients?]. / Streptococcus milleri. Ein Hinweis auf Karzinome im HNO-Bereich?

The Streptococcus milleri group, which also includes S. anginosus, S. intermedius and S. constellatus, is found in the oropharynx and gastrointestinal tract mucosa. Recent isolations of S. milleri DNA sequences have been made from both gastric and oesophageal carcinoma. There are only a few publications on the isolation of viable bacteria and S. milleri DNA, and their role in carcinogenesis, in otorhinolaryngologic malignoma. We present four patients with a cervical abscess and the isolation of S. milleri -group bacteria, without signs of malignancy or other risk factors. After a delay of several months, squamous cell carcinoma of the oropharynx was diagnosed in three patients and a neck metastasis without primary tumor in the fourth.

[Quantitative evaluation of Streptococcus mutans and Candida species and salivary factors in the oral cavity of patient undergoing radiotherapy]. / Avaliação quantitativa de Streptococcus do grupo mutans e Candida sp e fatores salivares na cavidade bucal de pacientes submetidos à radioterapia.

The aim of this study was to quantify the microorganisms Streptococcus mutans and Candida sp in the oral cavity of patients with oropharynx carcinoma, before, during and after radiotherapy, and to correlate the results with salivary factors such as pH, buffer capacity (CT) and flow rate (FS). Saliva samples were collected, diluted and inoculated in SB-20 agar and in Sabouraud agar, for Streptococcus mutans and Candida sp, respectively. Previously to dilution, the concentrated saliva was analyzed, and the salivary factors were determined. After the growth of colonies, the number of microorganisms was determined in CFU/ml. The analysis of the results allowed to conclude that the salivary factors are related to the presence of microorganisms, and that the number of CFU/ml increased as salivary flow rate decreased. The effects of radiation compromised salivary homeostasis and favored the increase of infection by yeasts and bacteria.