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Since the introduction of efficient anti-SARS-CoV-2 vaccines, the detection of antibodies becomes useful for immunological monitoring and COVID-19 control. Therefore, this longitudinal study aimed to evaluate the detection of SARS-CoV-2 antibodies in the serum and saliva of COVID-19-vaccinated adults. The study included 13 not vaccinated and 35 vaccinated participants with two doses of CoronaVac (Sinovac/Butantan) vaccine who subsequently received BNT162b2 (Pfizer-BioNTech) vaccine as a booster dose. Vaccinated participants donated saliva and serum in three different time points. Enzyme-linked immunosorbent assay was used for antibody detection. In our results, the serum neutralizing antibodies (NAb) were detected in 34/35 samples after second dose and in 35/35 samples one and five months after the booster dose. In saliva, NAb were detected in 30/35 samples after second dose and in 35/35 of samples one and five months after the booster dose. IgA was detected in 19/34 saliva samples after second dose, in 18/35 one month after the booster and in 30/35 five months after. IgG in saliva was detected in 1/34 samples after second dose, 33/35 samples one month after the booster dose and in 20/35 five months after. A strong correlation was found between IgG and neutralizing activity in saliva, and salivary IgA would be a sign of recent exposure to the virus. In conclusion, saliva can be suitable for monitoring antibodies anti-SARS-CoV-2 after vaccination. Heterologous vaccination contributed to increase anti-SARS-CoV-2 antibodies in the Brazilian health context. Complementary studies with large groups are mandatory to conclude the interest in following mucosal immunity.

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Since the introduction of efficient vaccines anti-SARS-CoV-2, antibody quantification becomes increasingly useful for immunological monitoring and COVID-19 control. In several situations, saliva samples may be an alternative to the serological test. Thus, this rapid systematic review aimed to evaluate if saliva is suitable for SARS-CoV-2 detection after vaccination. For this purpose, search strategies were applied at EMBASE, PubMed, and Web of Science. Studies were selected by two reviewers in a two-phase process. After selection, 15 studies were eligible and included in data synthesis. In total, salivary samples of approximately 1,080 vaccinated and/or convalescent individuals were analyzed. The applied vaccines were mostly mRNA-based (BioNTech 162b2 mRNA/Pfizer and Spikevax mRNA-1273/Moderna), but recombinant viral-vectored vaccines (Ad26. COV2. S Janssen - Johnson & Johnson and Vaxzevria/Oxford AstraZeneca) were also included. Different techniques were applied for saliva evaluation, such as ELISA assay, Multiplex immunoassay, flow cytometry, neutralizing and electrochemical assays. Although antibody titers are lower in saliva than in serum, the results showed that saliva is suitable for antibody detection. The mean of reported correlations for titers in saliva and serum/plasma were moderate for IgG (0.55, 95% CI 0.38-9.73), and weak for IgA (0.28, 95% CI 0.12-0.44). Additionally, six out of nine studies reported numerical titers for immunoglobulins detection, from which the level in saliva reached their reference value in four (66%). IgG but not IgA are frequently presented in saliva from vaccinated anti-COVID-19. Four studies reported lower IgA salivary titers in vaccinated compared to previously infected individuals, otherwise, two reported higher titers of IgA in vaccinated. Concerning IgG, two studies reported high antibody titers in the saliva of vaccinated individuals compared to those previously infected and one presented similar results for vaccinated and infected. The detection of antibodies anti-SARS-CoV-2 in the saliva is available, which suggests this type of sample is a suitable alternative for monitoring the population. Thus, the results also pointed out the possible lack of mucosal immunity induction after anti-SARS-CoV-2 vaccination. It highlights the importance of new vaccination strategies also focused on mucosal alternatives directly on primary routes of SARS-CoV-2 entrance. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022336968, identifier CRD42022336968.

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Metabolic alterations are a hallmark of the malignant transformation in cancer cells, which is characterized by multiple changes in metabolic pathways that are linked to macromolecule synthesis. This study aimed to explore whether salivary metabolites could help discriminate between breast cancer patients and healthy controls. Saliva samples from 23 breast cancer patients and 35 healthy controls were subjected to untargeted metabolomics using liquid chromatography-quadrupole time-of-flight mass spectrometry and a bioinformatics tool (XCMS Online), which revealed 534 compounds, characterized by their retention time in reverse-phase liquid chromatography and by the m/z ratio detected, that were shared by the two groups. Using the METLIN database, 31 compounds that were upregulated in the breast cancer group (p < 0.05) were identified, including seven oligopeptides and six glycerophospholipids (PG14:2, PA32:1, PS28:0, PS40:6, PI31:1, and PI38:7). In addition, pre-treatment and post-treatment saliva samples were analyzed for 10 patients who experienced at least a partial response to their treatment. In these patients, three peptides and PG14:2 were upregulated before but not after treatment. The area under the curve, sensitivity, and specificity for PG14:2 was 0.7329, 65.22%, and 77.14%, respectively. These results provide new information regarding the salivary metabolite profiles of breast cancer patients, which may be useful biomarkers.

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The early detection of breast cancer enables the use of less aggressive treatment and increases patient survival. The transmembrane glycoprotein mucin 1, which is also known as cancer antigen 15-3 (CA15-3), is aberrantly glycosylated and overexpressed in a variety of epithelial cancers, and serves a crucial role in the progression of the disease. CA15-3 is currently used as a marker of breast cancer. In the present study, CA15-3 concentrations in saliva and blood of patients with breast cancer were evaluated to test new assays to detect salivary CA15-3 in addition to ELISA and its diagnostic value. To the best of our knowledge, there are no previous reports of the use of chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLIA) in saliva. Saliva and blood were collected on the same day from patients with breast cancer (n=26) and healthy controls (n=28). For each subject, the level of serum CA15-3 was measured using ECLIA, and the level of salivary CA15-3 was measured using ECLIA, CLIA and enzyme-linked immunosorbent assay (ELISA). ELISA and CLIA were able to detect CA15-3 in saliva; however, ECLIA could not detect salivary CA15-3. There was no significant difference between the mean serum and salivary CA15-3 levels in patients with breast cancer or healthy controls. The levels of CA15-3 were highest for luminal breast cancer subtypes and stage IV cases. A moderate correlation was observed between salivary and serum CA15-3 levels as measured by ELISA in breast cancer patients (r=0.56; P=0.0047). The results demonstrated that ECLIA was not a good method to detect salivary CA15-3, although it is the gold standard for detecting serum CA15-3. The presence of CA15-3 in saliva was confirmed, and this will be useful in future research. Further investigations are necessary to confirm the ability to detect salivary CA15-3 and its correlation with serum CA15-3.

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Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case-control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and L-carnitine showed better discriminatory performance for early oral cancer.This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted.

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Salivary biomarkers could be helpful to characterize breast cancer. Therefore, this review was performed to evaluate the capability of salivary biological markers in the diagnosis and monitoring of breast cancer. Studies were eligible for inclusion if they assessed the potential diagnostic value or other discriminatory properties of biological markers in saliva of patients with breast cancer. The search was performed in six electronic databases (Cochrane, LILACS, PubMed, Science Direct, Scopus, Web of Science). In addition the biomarkers were classified according to their potential clinical application. We identified 567 pertinent studies, of which 13 met the inclusion criteria. Combined biomarker approaches demonstrated better ability to predict breast cancer patients than individual biomarkers. As single biomarker, namely proline, reported great capacity in both early and late stage breast cancer diagnosis. Taurine showed interesting capability to identify early breast cancer individuals. Furthermore, valine also demonstrated excellent diagnostic test accuracy for advanced stages of breast cancer. Only seven studies reported sensitivity and specificity (Zhang et al., 2010; Streckfus et al., 2000a; Brooks et al., 2008; Cheng et al., 2015; Bigler et al., 2002; Zhong et al., 2016; Streckfus, 2009), which varied considerably from 50% to 100%, and from 51% to 97%, respectively. In general, salivary biomarkers identified advanced stages of breast cancer better than early stages. There is currently limited evidence to confirm the putative implementation of salivary biomarkers as diagnostic tools for breast cancer. However, current review provides new research directions.

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