PAULO HENRIQUE BRAZ DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
ODE, FO - Docente
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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- High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania(2021) SUNDBERG, Jonas; OHMAN, Jenny; KORYTOWSKA, Magdalena; WALLSTROM, Mats; KJELLER, Goran; ANDERSSON, Maria; HORAL, Peter; LINDH, Magnus; GIGLIO, Daniel; KOVACS, Aniko; SAND, Lars; HIRSCH, Jan-Michael; FERRACINI, Lais Magda Araujo; SOUZA, Ana Carolina Mamana Fernandes de; PARLATESCU, Ioanina; DOBRE, Maria; HINESCU, Mihail-Eugen; BRAZ-SILVA, Paulo Henrique; TOVARU, Serban; HASSEUS, BengtObjectives Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. Patients and Methods A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL. Results In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. Conclusions In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.
- Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study(2021) KORYTOWSKA, Magdalena; SCHWAB, Gabriela; GIGLIO, Daniel; HIRSCH, Jan-Michael; HOLMBERG, Erik; KJELLER, Goran; SAND, Lars; WALLSTROM, Mats; OHMAN, Jenny; BRAZ-SILVA, Paulo; HASSEUS, BengtObjective: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. Methods: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. Results: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). Conclusion: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.
- EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation(2023) GANESH, Divya; DAFAR, Amal; NIKLASSON, Julia; SANDBERG, Ingrid; BRAZ-SILVA, Paulo; SAPKOTA, Dipak; OHMAN, Jenny; GIGLIO, Daniel; HASSEUS, BengtBackground/Aim: The EZH2 complex is involved in cellular proliferation and modulates the immune response in cancer. Less is known about the importance of EZH2 in precancerous lesions such as oral leukoplakia (OL). The aim of the study was to explore the association between EZH2 expression, immune activation, and cancer transformation in OL. Patients and Methods: Analyses were retrospectively performed on nine OL cases that had undergone transformation to oral squamous cell carcinoma (OSCC; OL-ca) and nine that had not undergone transformation (OL-non). EZH2-expressing cells, CD3+ and CD8+ T cells, and CD1a+ Langerhans cells were visualized with immunohistofluorescence and counted. Results: A moderate positive correlation between CD3-and EZH2-expressing and CD8-and EZH2-expressing cells in the epithelium was found (r=0.57, p=0.01; r=0.59, p=0.01). The number of EZH2-expressing cells in the epithelium of OL-ca was significantly higher compared to OL-non (p=0.0002). Cancer - free survival rates differed significantly between patients with EZH2high compared to EZH2low expression (p=0.001). EZH2high expression in OL epithelium was associated with a 13-fold higher risk for developing OSCC (HR=12.8). Conclusion: EZH2 expression in oral epithelium predicts OSCC transformation of OL and correlates with the level of T-cell infiltration.
- COVID-19 salivary signature: diagnostic and research opportunities(2021) SAPKOTA, Dipak; SOLAND, Tine Merete; GALTUNG, Hilde Kanli; SAND, Lars Peter; GIANNECCHINI, Simone; TO, Kelvin K. W.; MENDES-CORREA, Maria Cassia; GIGLIO, Daniel; HASSEUS, Bengt; BRAZ-SILVA, Paulo HenriqueThe COVID-19 (caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) epidemic started in Wuhan (Hubei Province, China) in mid-December 2019 and quickly spread across the world as a pandemic. As a key to tracing the disease and to implement strategies aimed at breaking the chain of disease transmission, extensive testing for SARS-CoV-2 was suggested. Although nasopharyngeal/oropharyngeal swabs are the most commonly used biological samples for SARS-CoV-2 diagnosis, they have a number of limitations related to sample collection and healthcare personnel safety. In this context, saliva is emerging as a promising alternative to nasopharyngeal/oropharyngeal swabs for COVID-19 diagnosis and monitoring. Saliva collection, being a non-invasive approach with possibility for self-collection, circumvents to a great extent the limitations associated with the use of nasopharyngeal/oropharyngeal swabs. In addition, various salivary biomarkers including the salivary metabolomics offer a high promise to be useful for better understanding of COVID-19 and possibly in the identification of patients with various degrees of severity, including asymptomatic carriers. This review summarises the clinical and scientific basis for the potential use of saliva for COVID-19 diagnosis and disease monitoring. Additionally, we discuss saliva-based biomarkers and their potential clinical and research applications related to COVID-19.
- Expression profile of SARS-CoV-2 cellular entry proteins in normal oral mucosa and oral squamous cell carcinoma(2022) SAPKOTA, Dipak; SHARMA, Sunita; SOLAND, Tine M.; BRAZ-SILVA, Paulo H.; TEH, Muy-TeckObjective: Besides angiotensin converting enzyme 2 (ACE2), an active involvement of proteases (FURIN and/or TMPRSS2) is important for cellular entry of SARS-CoV-2. Therefore, a simultaneous expression profiling of entry proteins in a tissue might provide a better risk assessment of SARS-CoV-2 infection as compared to individual proteins. In an attempt to understand the relative susceptibility of oral squamous cell carcinoma (OSCC) lesions as compared to the normal oral mucosa (NOM) for SARS-CoV-2 attachment/entry, this study examined the mRNA and protein expression profiles of ACE2, FURIN, and TMPRSS2 in the corresponding tissues using public transcriptomic and proteomics datasets. Methods and methods: Public transcriptomic and proteomics datasets (the Cancer Genome Atlas (TCGA)/the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), and two independent microarray datasets) were used to examine the expression profiles of ACE2, TMPRSS2 and FURIN in NOM and OSCC. Results: ACE2, TMPRSS2, and FURIN mRNAs were detected in NOM, however, at lower levels as compared to other body tissues. Except for moderate up-regulation of FURIN, expression levels of ACE2 and TMPRSS2 mRNA were unchanged/downregulated in OSCC as compared to the NOM. Conclusions: These results indicate that NOM may serve as a possible site for SARS-CoV-2 attachment, however, to a lesser extent as compared to organs with higher expression levels of the SARS-CoV-2 entry proteins. However, the evidence is lacking to suggest that expression status of entry proteins predisposes OSCC lesions to additional risk for SARS-CoV-2 attachment/entry as compared to NOM.
- Lack of direct association between oral mucosal lesions and SARS-CoV-2 in a cohort of patients hospitalised with COVID-19(2022) SCHWAB, Gabriela; PALMIERI, Michelle; ZERBINATI, Rodrigo M.; SARMENTO, Dmitry J. S.; REIS, Thais; ORTEGA, Karem L.; KANO, Italo T.; V, Rafael A. Caixeta; HASSEUS, Bengt; SAPKOTA, Dipak; JUNGES, Roger; GIANNECCHINI, Simone; COSTA, Andre L. F.; JALES, Sumatra M. C. P.; LINDOSO, Jose A. L.; GALLO, Camila Barros; BRAZ-SILVA, Paulo H.Background COVID-19 is a disease affecting various human organs and systems, in which the virus seeks to interact with angiotensin-converting enzyme 2 receptors. These receptors are present in the oral cavity, but the direct relationship between such an interaction and possible oral manifestations of COVID-19 is still unclear. Aim The present study evaluated oral manifestations in a cohort of COVID-19 patients during the period of hospitalisation. Methods In total, 154 patients presenting moderate-to-severe forms of COVID-19 had their oral mucosa examined twice a week until the final outcome, either discharge or death. The oral alterations observed in the patients were grouped into Group 1 (pre-existing conditions and opportunistic oral lesions) and Group 2 (oral mucosal changes related to hospitalization). Results Oral lesions found in the patients of Group 1 are not suggestive of SARS-CoV-2 infection as they are mainly caused by opportunistic infections. On the other hand, oral alterations found in the patients of Group 2 were statistically (P < 0.001) related to intubation and longer period of hospitalisation. Conclusion It is unlikely that ulcerative lesions in the oral cavity are a direct manifestation of SARS-CoV-2 or a marker of COVID-19 progression.
- Performance of at-home self-collected saliva and nasal-oropharyngeal swabs in the surveillance of COVID-19(2021) BRAZ-SILVA, Paulo H.; MAMANA, Ana C.; ROMANO, Camila M.; FELIX, Alvina C.; V, Anderson de Paula; FEREIRA, Noeli E.; BUSS, Lewis F.; TOZETTO-MENDOZA, Tania R.; V, Rafael A. Caixeta; LEAL, Fabio E.; GRESPAN, Regina M. Z.; BIZARIO, Joao C. S.; FERRAZ, Andrea B. C.; SAPKOTA, Dipak; GIANNECCHINI, Simone; TO, Kelvin K.; DOGLIO, Alain; MENDES-CORREA, Maria C.Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar (R) SARS-CoV-2 RT-PCR Kit 1.0. Results: There was an overall significant agreement (kappa coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.