Longitudinal study of the role of salivary proteins on radiation-related caries onset in head and neck cancer patients using 5000 ppm fluoride dentifrice up to one-year post-intensity modulated radiotherapy.

OBJECTIVES: Longitudinal assessment of the role of specific proteins on radiotherapy caries (RC) onset in head and neck cancer patients(HNC) up to one-year post-IMRT using a 5000ppm fluoride paste daily. MATERIALS AND METHODS: Dental status/salivary protein data were obtained from 40 HNC patients pre-IMRT, six months (T1) and 12 months (T2) post-IMRT (ethical approval/consent). DMFT/salivary parameters were quantified, including flow rate, mucin 5B/7, Immunoglobulin A (IgA), cystatin S and α-amylase. RESULTS: 45% patients had at least one carious lesion at T2, a significant reduction in the number of remaining teeth (65% <21), salivary flow rate (< 50%) and, protein secretion (< 0.05) post-IMRT. T1 IgA concentration/secretion rate was associated with RC (p < 0.05). Finally, IgA and total protein concentration obtained at T1 could provide a predictive pattern (AUC 82.3%) for the patients more predisposed to developing RC at T2. CONCLUSIONS: This study demonstrated the significant association of RC with salivary proteins in HNC patients treated with IMRT, revealing the potential role of salivary proteins in the early diagnosis of RC. CLINICAL RELEVANCE: This research contributes to revealing salivary proteins association with RC, and its role in early diagnosis. Therefore, this could be the first step towards personalized medicine approaches to improve this group quality-of-life.

Nanomaterial Biosensors in Salivary Diagnosis of Oral Cancer: A Scoping Review.

Oral cancer is among the highest in the Indian subcontinent. Advanced stages of oral cancer are associated with severe morbidity and higher mortality. Salivary diagnosis is novel and non-invasive. It could be employed on patients even with restricted mouth opening. Hence, an attempt was made to retrieve relevant data regarding this clinically relevant topic.  This article has reviewed metal oxide nanoparticles as a biosensor (BS) in salivary diagnosis for oral cancer. Gold, copper oxide, and carbon nanotubes (CNTs) were used in BS applications. A search from the PUBMED database collection (2004 to 2024) was performed to identify the nanoparticle biomarkers and salivary diagnosis in oral cancer. It revealed 30 articles. All the relevant data was extracted and tabulated in this review. We have discussed the relevance of these BS in salivary diagnosis with their corresponding clinical parameters and sensitivity. We hope that this review summarizes the available literature on this topic and incites dedicated research in prompt and early diagnosis of oral cancer, which directly influences the quality of life outcomes in such patients.

Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment.

For many diseases, and cancer in particular, early diagnosis allows a wider range of therapies and a better disease management. This has led to improvements in diagnostic procedures, most often based on tissue biopsies or blood samples. Other biological fluids have been used to diagnose disease, and among them saliva offers a number of advantages because it can be collected non-invasively from large populations at relatively low cost. To what extent might saliva content reveal the presence of a tumour located at a distance from the oral cavity and the molecular information obtained from saliva be used to establish a diagnosis are current questions. This review focuses primarily on the content of saliva and shows how it potentially offers a source of diagnosis, possibly at an early stage, for pathologies such as cancers or endometriosis.

Letter to the Editor, "Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis".

This article is temporarily under embargo.

Normative Values of the Repetitive Saliva Swallow Test and Clinical Factors Affecting the Test Scores in Healthy Adults.

The Repetitive Saliva Swallow Test (RSST) is a screening test for oropharyngeal dysphagia during which the subject is asked to perform as many empty swallows as possible in 30 s. Previous validation studies found a cutoff value of 3 > swallows as pathological. The aims of this study were to establish the normative values of the RSST and to examine the effect of clinical factors on RSST scores in healthy adults. A cross-sectional study of 280 adults. An equal number of females and males were recruited for each decade of life, ages 20 to 90 years. Patients reporting swallowing difficulties, history of neurologic disorders, or head and neck surgery or radiation were excluded. Data collected included RSST scores, number and type of comorbidities, number of prescribed medications, body mass index, smoking habits, and self-assessment xerostomia questionnaire. The mean RSST score for the entire cohort was 7.01 ± 2.86. Males had a higher RSST score (7.6 ± 3.04 compared to 6.47 ± 2.56, p = 0.001). Age showed an inverse correlation with RSST scores (Pearson's Correlation Coefficient (PCC) = -0.463, p < 0.0001), as well as body mass index, BMI (PCC = -0.2, p < 0.0001), number of co-morbidities (PCC=-0.344, p < 0.0001) and number of prescribed medications (PCC= -0.425, p < 0.0001). Self-reported amount of saliva positively correlated (PCC = 1.05, p = 0.04) with RSST scores. A multivariate logistic regression analysis was performed. Age, sex, BMI, and number of prescribed medications were found as significant independent factors on RSST scores. RSST scores in healthy adults decline with age and are lower in females, individuals taking multiple medications and with higher BMI. Mean RSST for all age groups did not fall beneath the previously established pathological cut-off.

Alterations of mannosylated glycopatterns recognized by Hippeastrum hybrid lectin in saliva of patients with lung cancer.

OBJECTIVES: Lung cancer (LC) is the malignant tumor with the highest mortality rate worldwide, and precise early diagnosis can improve patient prognosis. The purpose of this study was to investigate whether alterations in the glycopatterns recognized by the Hippeastrum hybrid lectin (HHL) in salivary proteins are associated with the development of LC. MATERIALS AND METHODS: First, we collected saliva samples from LC (15 lung adenocarcinoma (ADC); 15 squamous cell carcinoma (SCC); 15 small cell lung cancer (SCLC)) and 15 benign pulmonary disease (BPD) for high-throughput detection of abundance levels of HHL-recognized glycopatterns using protein microarrays, and then validated the pooled samples from each group with lectin blotting analysis. Finally, the N-glycan profiles of salivary glycoproteins isolated from the pooled samples using HHL-magnetic particle conjugates were characterized separately using MALDI-TOF/TOF-MS. RESULTS: The results showed that the abundance level of glycopatterns recognized by HHL in salivary proteins was elevated in LC compared to BPD. The proportion of mannosylated N-glycans was notably higher in ADC (31.7%), SCC (39.0%), and SCLC (46.6%) compared to BPD (23.3%). CONCLUSIONS: The altered salivary glycopatterns such as oligomannose, Manα1-3Man, or Manα1-6Man N-glycans recognized by HHL might serve as potential biomarkers for the diagnosis of LC patients. CLINICAL RELEVANCE: This study provides crucial information for studying changes in salivary to differentiate between BPD and LC and facilitate the discovery of biomarkers for LC diagnosis based on precise alterations of mannosylated N-glycans in saliva.

A one-step low-cost molecular test for SARS-CoV-2 detection suitable for community testing using minimally processed saliva.

The gold standard for coronavirus disease 2019 diagnostic testing relies on RNA extraction from naso/oropharyngeal swab followed by amplification through reverse transcription-polymerase chain reaction (RT-PCR) with fluorogenic probes. While the test is extremely sensitive and specific, its high cost and the potential discomfort associated with specimen collection made it suboptimal for public health screening purposes. In this study, we developed an equally reliable, but cheaper and less invasive alternative test based on a one-step RT-PCR with the DNA-intercalating dye SYBR Green, which enables the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from saliva samples or RNA isolated from nasopharyngeal (NP) swabs. Importantly, we found that this type of testing can be fine-tuned to discriminate SARS-CoV-2 variants of concern. The saliva RT-PCR SYBR Green test was successfully used in a mass-screening initiative targeting nearly 4500 asymptomatic children under the age of 12. Testing was performed at a reasonable cost, and in some cases, the saliva test outperformed NP rapid antigen tests in identifying infected children. Whole genome sequencing revealed that the antigen testing failure could not be attributed to a specific lineage of SARS-CoV-2. Overall, this work strongly supports the view that RT-PCR saliva tests based on DNA-intercalating dyes represent a powerful strategy for community screening of SARS-CoV-2. The tests can be easily applied to other infectious agents and, therefore, constitute a powerful resource for an effective response to future pandemics.

Performance and overview of clinically relevant areas of application of saliva testing in the cat.

Introduction: The cat represents an important model in order to investigate basic physiological knowledge of salivary secretion as well as pharmacokinetics of active substances. Objective: The aim of the study was to review in which diagnostic application areas saliva testing is routinely used and in which areas it could be further explored in the future. Materials and methods: Literature relevant to the research question was collected in March 2022 using the Pubmed database. Results: The diagnosis of infectious diseases in cat saliva is one of the most important fields of application. Saliva diagnostics may also indicate dental diseases, allergies or kidney and other metabolic diseases. Sexual and stress hormones can also be measured in cat saliva. A number of clinically relevant allergens in cat saliva that may cause allergies in humans has been investigated and described, in addition to infectious agents that can be transmitted from cats to humans. Conclusions: Saliva testing in cats can be useful in many areas, including the detection of infectious diseases, allergies and dental disease. However, it is far from being used to its full potential within veterinary medicine.

Spicy Recipe for At-Home Diagnostics: Smart Salivary Sensors for Point-of-Care Diagnosis of Jaundice.

Even though significant advances have been made, there is still a lack of reliable sensors capable of noninvasively monitoring bilirubin and diagnosing jaundice as the most common neonatal disease, particularly at the point-of-care (POC) where blood sampling from infants is accompanied by serious challenges and concerns. Herein, for the first time, using an easy-to-fabricate/use assay, we demonstrate the capability of curcumin embedded within paper for noninvasive optical monitoring of bilirubin in saliva. The highly selective sensing of the developed sensor toward bilirubin is attributed to bilirubin photoisomerization under blue light exposure, which can selectively restore the bilirubin-induced quenched fluorescence of curcumin. We also fabricated an IoT-enabled hand-held optoelectronic reader to measure and quantify the fluorescence and color signals of our sensor. Clinical analysis on the saliva of 18 jaundiced infants by using our developed smart salivary sensor proved that it is amenable to be widely exploited in POC applications for bilirubin monitoring as there are good correlations between its results with those of reference methods in saliva and blood. Meeting all WHO's REASSURED criteria by our developed sensor makes it a highly promising sensor for smart noninvasive diagnosis and therapeutic monitoring of jaundice, hepatitis, and other bilirubin-induced neurologic diseases at the POC.

Salivary IgG and IgA in newborn calves and the possible role in the assessment of passive immunity transfer.

Introduction: The transfer of immunoglobulins from the mother to newborns is widely recognized as a critical event for safeguarding offspring against potentially life-threatening infectious diseases. Mainly for this reason, this study aimed to assess the concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in the saliva of newborn calves and explore its potential use for monitoring passive immunity transfer from cows to calves, as also to evaluate how colostrum intake affects serum and saliva IgG and IgA concentrations. Methods: The quality of colostrum samples was evaluated using an optical refractometer before administration to the calves. Saliva and blood samples from 24 calves were obtained at the day of birth (T0) and 2 days after (T2) for determination of serum concentrations of total protein by refractometer, IgG and IgA (both on serum and saliva) by ELISA test. Results: Positive correlations were observed between salivary IgA at T2 and salivary IgG at T2. A significant increase in both IgG and IgA levels in calf serum and saliva was noted. Salivary IgA levels can reflect salivary IgG levels. Discussion: These findings suggest the potential utility of IgA in monitoring passive immunity transfer, and do not exclude saliva as an alternative, practical, and non-invasive matrix for assessing passive immunity transfer.

Single-molecule characterization of salivary protein aggregates from Parkinson's disease patients: a pilot study.

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-ß peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-ß aggregate ratio is increased almost 2-fold in patients with Parkinson's disease (n = 20) compared with controls (n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-ß aggregates than control saliva (P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease (n = 17) and controls (n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods.

Stability of influenza A virus in droplets and aerosols is heightened by the presence of commensal respiratory bacteria.

Aerosol transmission remains a major challenge for control of respiratory viruses, particularly those causing recurrent epidemics, like influenza A virus (IAV). These viruses are rarely expelled alone, but instead are embedded in a consortium of microorganisms that populate the respiratory tract. The impact of microbial communities and inter-pathogen interactions upon stability of transmitted viruses is well-characterized for enteric pathogens, but is under-studied in the respiratory niche. Here, we assessed whether the presence of five different species of commensal respiratory bacteria could influence the persistence of IAV within phosphate-buffered saline and artificial saliva droplets deposited on surfaces at typical indoor air humidity, and within airborne aerosol particles. In droplets, presence of individual species or a mixed bacterial community resulted in 10- to 100-fold more infectious IAV remaining after 1 h, due to bacterial-mediated flattening of drying droplets and early efflorescence. Even when no efflorescence occurred at high humidity or the bacteria-induced changes in droplet morphology were abolished by aerosolization instead of deposition on a well plate, the bacteria remained protective. Staphylococcus aureus and Streptococcus pneumoniae were the most stabilizing compared to other commensals at equivalent density, indicating the composition of an individual's respiratory microbiota is a previously unconsidered factor influencing expelled virus persistence.IMPORTANCEIt is known that respiratory infections such as coronavirus disease 2019 and influenza are transmitted by release of virus-containing aerosols and larger droplets by an infected host. The survival time of viruses expelled into the environment can vary depending on temperature, room air humidity, UV exposure, air composition, and suspending fluid. However, few studies consider the fact that respiratory viruses are not alone in the respiratory tract-we are constantly colonized by a plethora of bacteria in our noses, mouth, and lower respiratory system. In the gut, enteric viruses are known to be stabilized against inactivation and environmental decay by gut bacteria. Despite the presence of a similarly complex bacterial microbiota in the respiratory tract, few studies have investigated whether viral stabilization could occur in this niche. Here, we address this question by investigating influenza A virus stabilization by a range of commensal bacteria in systems representing respiratory aerosols and droplets.

Integration of a Cas12a-mediated DNAzyme actuator with efficient RNA extraction for ultrasensitive colorimetric detection of viral RNA.

Developing highly sensitive and specific on-site tests is imperative to strengthen preparedness against future emerging infectious diseases. Here, we describe the construction of a Cas12a-mediated DNAzyme actuator capable of converting the recognition of a specific DNA sequence into an amplified colorimetric signal. To address viral RNA extraction challenges for on-site applications, we developed a rapid and efficient method capable of lysing the viral particles, preserving the released viral RNA, and concentrating the viral RNA. Integration of the DNAzyme actuator with the viral RNA extraction method and loop-mediated isothermal amplification enables a streamlined colorimetric assay for highly sensitive colorimetric detection of respiratory RNA viruses in gargle and saliva. This assay can detect as few as 83 viral particles/100 µL in gargle and 166 viral particles/100 µL in saliva. The entire assay, from sample processing to visual detection, was completed within 1 h at a single controlled temperature. We validated the assay by detecting SARS-CoV-2 in 207 gargle and saliva samples, achieving a clinical sensitivity of 96.3 % and specificity of 100%. The assay is adaptable for detecting specific nucleic acid sequences in other pathogens and is suitable for resource-limited settings.

Effect of casozepine administration on stress in dogs during a veterinary examination - A randomized placebo-controlled trial.

The aim of the study was to investigate the stress-reducing effect of a casozepine before a veterinary examination in dogs. It should be examined whether the dogs are less stressed during a standardized veterinary examination after an oral application of casozepine over 2 days and whether the administration has an influence on the salivary concentrations of the stress hormones vasopressin and cortisol. Across the study group (n=36), a significantly lower stress score (P=0.0026) and lower mean (P=0.01) and maximum (P=0.024) pulse rates were seen at follow-up after casozepine administration, in contrast to the placebo group (n=26). Salivary vasopressin concentrations increased during follow-up in the placebo group (P=0.04), whereas they remained the same in the casozepine group. Cortisol concentrations increased during follow-up in the casozepin group (P=0.01). The results indicate that although dogs in both groups remained excited at follow-up, short-term casozepine administration before a veterinary visit had a weak stress-reducing effect in dogs based on subjective stress scoring and pulse rate.

In vivo modification of the enamel pellicle and saliva resveratrol levels after use of resveratrol-containing orodispersible capsules.

OBJECTIVES: To evaluate in vivo 1) the bioavailability of trans-resveratrol when administered through sublingual capsules; 2) the effect of resveratrol on the protein composition of the acquired enamel pellicle (AEP). DESIGN: Ten volunteers received a sublingual capsule containing 50 mg of trans-resveratrol. Unstimulated saliva was then collected after 0, 30, 60, and 120 min and AEP was collected after 120 min following administration of the capsule. In the next week, the volunteers received a placebo sublingual capsule, and saliva and AEP were collected again. Saliva samples were analyzed for free trans-resveratrol using high-performance liquid chromatopgraphy (HPLC), and AEP samples were subjected to proteomic analysis (nLC-ESI-MS/MS). RESULTS: Trans-resveratrol was detected in saliva at all the time points evaluated, with the peak at 30 min. A total of 242 proteins were identified in both groups. Ninety-six proteins were increased and 23 proteins were decreased in the Resveratrol group. Among the up-regulated proteins, isoforms of cystatins, PRPs, Mucin-7, Histatin-1, Lactotrasnferrin and Lysozyme-C were increased and the isoforms of Protein S100, Neutrophil defensins, Albumin, PRPs, and, Statherin were decreased in Resveratrol group. CONCLUSION: The sublingual capsule is effective at increasing the bioavailability of trans-resveratrol in saliva. Several proteins involved in important processes to maintain systemic and oral health homeostasis were identified. These proteins differently expressed due to the presence of trans-resveratrol deserve attention for future studies, since they have important functions, mainly related to antimicrobial action.

Salivary buffering capacity is correlated with umami but not sour taste sensitivity in healthy adult Japanese subjects.

OBJECTIVE: Saliva serves multiple important functions crucial for maintaining a healthy oral and systemic environment. Among them, the pH buffering effect, which is primarily mediated by bicarbonate ions, helps maintain oral homeostasis by neutralizing acidity from ingested foods. Therefore, higher buffering capacity, reflecting the ability to neutralize oral acidity, may influence taste sensitivity, especially for sour taste since it involves sensing H+ ions. This study aims to explore the relationship between salivary buffering capacity and taste sensitivities to the five basic tastes in healthy adult humans. DESIGN: Eighty seven healthy adult students participated in this study. Resting saliva volume was measured using the spitting method. The liquid colorimetric test was used to assess salivary buffering capacity. The whole-mouth taste testing method was employed to determine the recognition threshold for each tastant (NaCl, sucrose, citric acid, quinine-HCl, monosodium glutamate). RESULTS: Taste recognition thresholds for sour taste as well as sweet, salty, and bitter tastes showed no correlation with salivary buffering capacity. Interestingly, a negative relationship was observed between recognition threshold for umami taste and salivary buffering capacity. Furthermore, a positive correlation between salivary buffering capacity and resting saliva volume was observed. CONCLUSIONS: Salivary buffering capacity primarily influences sensitivity to umami taste, but not sour and other tastes.

Welfare Assessment in Pigs Using the Salivary Proteome.

Identifying the potential presence of stress at the pig farm is fundamental since it affects pig welfare. As a result, a reliable and straightforward tool to monitor stress could record the welfare status of the animals. Although numerous methods to assess the welfare of pigs have been developed in the past, no gold standard has been established yet. Recently, the value of saliva as a tool to identify chronic stress in piglets was explored, as it can be collected fast and non-invasively. Since the protein composition, i.e., the proteome of porcine saliva, responds to stress, the affected proteins could be used as salivary stress biomarkers. The present review first defines stress and its relationship with welfare. Next, the porcine gland-specific salivary proteome is characterized. Finally, six potential salivary biomarkers for stress are proposed, i.e., odorant-binding protein, vomeromodulin-like protein, chitinase, lipocalin-1, long palate lung and nasal epithelium protein, and alpha-2-HS-glycoprotein.

Electrochemical dissolution and retrieval of broken NiTi endodontic files from root canal using chloride based isotonic fluids as electrolytes - An in vitro study.

Objective: The electrochemical dissolution method of instrument retrieval emphasizes on the dissolution of the instrument rather than sacrificing dentine. Most of the studies conducted for electrochemical dissolution used fluoride-containing electrolytes and were performed inside a beaker. In this study, we used chloride-based fluids as electrolytes. Materials and Methods: Fifty extracted mandibular first premolars were divided into five groups based on the electrolytes used. Canals were enlarged to ProTaper Universal F2, and files were intentionally broken inside the canal. These specimens were subjected to electrochemical characterization by applying the potential of 9V for 20 min. Optical images were taken to assess the change in surface topography. The results were analyzed statistically by one-way analysis of variance (analysis of variance [ANOVA]). Results: The rate of dissolution based on the electrolyte used decreased in the following order, viz. Tyrode's solution>artificial saliva>normal saline>Ringer's lactate/physiological serum. Conclusion: Apart from fluoride, chloride-based electrolytes could be an efficient alternative.

Unveiling the In Vitro Anti-Biofilm Potential of Lactobacillus rhamnosus Against Saliva-Based Pathogens: A Gender-Age-Area Specific Study.

Probiotics, like lactobacilli and bifidobacteria, benefit health by populating the digestive system, which houses numerous microbial species. Studies demonstrate their ability to inhibit biofilm formation, crucial in preventing oral conditions like dental caries. Our research evaluated a probiotic strain's anti-biofilm efficacy against oral pathogens in 45 individuals' saliva, alongside its biofilm-forming potential. Analysis revealed significant biofilm inhibition in 36 samples. Comparisons based on age, gender, and geography further supported these findings. We propose further exploration of probiotics tailored to specific demographics to enhance oral health outcomes, suggesting a promising avenue for preventing oral microbial diseases.

Oral microbial dysbiosis in patients with oral cavity cancers.

OBJECTIVES: The pathogenesis of oral cavity cancers is complex. We tested the hypothesis that oral microbiota dysbiosis is associated with oral cavity cancer. MATERIALS AND METHODS: Patients with primary oral cavity cancer who met the inclusion and exclusion criteria were included in the study. Matching healthy individuals were recruited as controls. Data on socio-demographic and behavioral factors, self-reported periodontal measures and habits, and current dental status were collected using a structured questionnaire and periodontal chartings. In addition to self-reported oral health measures, each participant received a standard and detailed clinical examination. DNA was extracted from saliva samples from patients and healthy controls. Next-generation sequencing was performed by targeting V3-V4 gene regions of the 16 S rRNA with subsequent bioinformatic analyses. RESULTS: Patients with oral cavity cancers had a lower quality of oral health than healthy controls. Proteobacteria, Aggregatibacter, Haemophilus, and Neisseria decreased, while Firmicutes, Bacteroidetes, Actinobacteria, Lactobacillus, Gemella, and Fusobacteria increased in oral cancer patients. At the species level, C. durum, L. umeaens, N. subflava, A. massiliensis, and V. dispar were significantly lower, while G. haemolysans was significantly increased (p < 0.05). Major periodontopathogens associated with periodontal disease (P. gingivalis and F.nucleatum) increased 6.5- and 2.8-fold, respectively. CONCLUSION: These data suggested that patients with oral cancer had worse oral health conditions and a distinct oral microbiome composition that is affected by personal daily habits and may be associated with the pathogenicity of the disease and interspecies interactions. CLINICAL RELEVANCE: This paper demonstrates the link between oral bacteria and oral cancers, identifying mechanistic interactions between species of oral microbiome.