LUISA LINA VILLA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
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- Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn?s disease patients?(2022) GUZELA, V. R.; SOBRADO JR., C. W.; NADAL, S. R.; VILLA, L. L.; MOTA, G. R.; GONCALVES, A. P.; NADAL, C. R. M.; NAHAS, C. S. R.; NAHAS, S. C.The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn???s disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.
- Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16(INK4a) status(2022) SICHERO, Laura; TAGLIABUE, Marta; MOTA, Giana; FERREIRA, Silvaneide; NUNES, Rafaella A. L.; CASTANEDA, Carlos Arturo; CASTILLO, Miluska; CORREA, Rita Mariel; PERDOMO, Sandra; RODRIGUEZ-URREGO, Paula A.; MATOS, Leandro Luongo; MOHSSEN, Ansarin; GHEIT, Tarik; TOMMASINO, Massimo; CHIOCCA, Susanna; VILLA, Luisa LinaBackground Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16(INK4a) in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. Methods HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16(INK4a) immunohistochemistry. Results HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16(INK4a) positivity were observed among HPV positive OPC/OCC cases compared to LC cases. Conclusions Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.
conferenceObject National prevalence of oral HPV infection in vaccinated and unvaccinated young adults in Brazil(2021) KOPS, Natalia Luiza; COMERLATO, Juliana; BANDEIRA, Isabel; BESSEL, Marina; MARANHAO, Ana Goretti Kalume; VILLA, Luisa Lina; MOTA, Giana; SOUZA, Flavia Moreno Alves de; PEREIRA, Gerson Fernando Mendes; WENDLAND, Eliana- Human Papillomavirus Positivity at 3 Anatomical Sites Among Transgender Women in Central Brazil(2023) OLIVEIRA, Brunna Rodrigues de; SILVA, Bruno Vinicius Diniz E.; SANTOS, Kamila Cardoso dos; CAETANO, Karlla Antonieta Amorim; MOTA, Giana; SADDI, Vera Aparecida; RABELO-SANTOS, Silvia Helena; VILLA, Luisa Lina; VADDIPARTI, Krishna; COOK, Robert L.; TELES, Sheila Araujo; CARNEIRO, Megmar Aparecida dos SantosBackgroundTransgender women (TGW) are susceptible to the acquisition of sexually transmitted infections (STIs), including human papillomavirus (HPV). Nonetheless, the exact data for this population are scarce. We estimated HPV positivity at the anal, genital, and oral sites among TGW and also identified the related characteristics and behaviors that could be risk factors for HPV infection in a sample of TGW in Brazil. Furthermore, we characterized the site-specific HPV genotypes among those who were positive for HPV at these 3 sites.MethodsA cross-sectional study was conducted on TGW in Goiania City (Central-Midwest region), Brazil, between April 2018 and August 2019. Respondent-driven sampling was applied for recruitment. Next, self-collected anal, genital, and oral samples were examined for HPV DNA using polymerase chain reaction (SPF-10 primer). Human papillomavirus genotypes were identified in 12 TGW.ResultsIn the TGW included in the study, the anal, genital, and oral HPV positivity values were 77.2% (95% confidence interval [CI], 67.3%-84.6%), 33.5% (95% CI, 26.1%-48.9%), and 10.9% (95% CI, 5.8%-17.0%), respectively. In addition, the majority of 12 participants who tested for HPV had multiple genotypes. HPV-52 was the most prevalent genotype identified at the anal (66.6%) and genital (40.0%) sites, whereas HPV-62 and HPV-66 were the most common at the oral site (25.0%).ConclusionsA high HPV positivity was observed among TGW. Therefore, additional epidemiological studies on HPV genotypes should generate health intervention information, including the prevention, diagnosis, and treatment of sexually transmitted infections.
- Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV in the anorectal fistula tract. A comparative study(2023) BOARINI, Lucas Rodrigues; SOBRADO, Carlos Walter; MOTA, Giana Rabello; VILLA, Luisa Lina; ALBUQUERQUE, Idblan Carvalho de; QUEIROZ, Natalia Sousa Freitas; FACANALI, Carolina Bortolozzo Graciolli; NADAL, Sidney Roberto; CECCONELLO, IvanBackground & Aims: Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group. Methods: The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test. Results: A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group (33.3% vs. 16.7%; p = 0.046). Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease (OR = 3.29; 95% CI 1.20-9.01), regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%). Conclusion: Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease.
- Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils(2017) ALVAREZ, Karla Lucia Fernandez; BELDI, Mariana; SARMANHO, Fabiane; ROSSETTI, Renata Ariza Marques; SILVEIRA, Caio Raony Farina; MOTA, Giana Rabello; ANDREOLI, Maria Antonieta; CARUSO, Eliana Dias de Carvalho; KAMILLOS, Marcia Ferreira; SOUZA, Ana Marta; MASTROCALLA, Haydee; CLAVIJO-SALOMON, Maria Alejandra; BARBUTO, Jose Alexandre Marzagao; LORENZI, Noely Paula; LONGATTO-FILHO, Adhemar; BARACAT, Edmund; LOPEZ, Rossana Veronica Mendoza; VILLA, Luisa Lina; TACLA, Maricy; LEPIQUE, Ana PaulaCervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
- Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer(2020) ROSSETTI, Renata A. M.; SILVA-JUNIOR, Ildefonso A. da; RODRIGUEZ, Gretel R; ALVAREZ, Karla L. F.; STONE, Simone C.; CIPELLI, Marcella; SILVEIRA, Caio R. F.; BELDI, Mariana Carmezim; MOTA, Giana R.; MARGARIDO, Paulo F. R.; BARACAT, Edmund C.; UNO, Miyuki; VILLA, Luisa L.; CARVALHO, Jesus P.; YOKOCHI, Kaori; ROSA, Maria Beatriz S. F.; LORENZI, Noely P.; LEPIQUE, Ana PaulaCervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NF kappa B, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NF kappa B decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NF kappa B partially reversed these effects. This study indicates that STAT3 and NF kappa B are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.
- Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil(2024) SICHERO, Laura; GONCALVES, Milena Giulia; BETTONI, Fabiana; COSER, Elisangela Monteiro; MOTA, Giana; NUNES, Rafaella A. L.; MERCANTE, Ana Maria da Cunha; NATALINO, Renato; UNO, Miyuki; ALVES, Maria Jose Ferreira; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; KULCSAR, Marco Aurelio Vamondes; ALVARENGA, Gustavo Fernandes de; HOEFLER, Daniela; SCHROEDER, Lea; WATERBOER, Tim; TOMMASINO, Massimo; VILLA, Luisa LinaBackground: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16(INK4a) status was also accessed. Methods: HPV was genotyped by PCR-hybridization. All HPV DNA positive and similar to 10 % HPV DNA negative cases underwent p16(INK4a) immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. Results: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16(INK4) (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. Conclusions: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.