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
20 resultados
Resultados de Busca
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- Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women(2021) WENDLAND, Eliana M.; KOPS, Natalia Luiza; BESSEL, Marina; COMERLATO, Juliana; MARANHAO, Ana Goretti Kalume; SOUZA, Flavia Moreno Alves; VILLA, Luisa Lina; PEREIRA, Gerson Fernando MendesWe examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era. (C) 2021 The Author(s).
- E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes(2021) NUNES, Emily Montosa; TALPE-NUNES, Valeria; SOBRINHO, Joao Simao; FERREIRA, Silvaneide; LINO, Vanesca de Souza; TERMINI, Lara; SILVA, Gabriela Avila Fernandes; BOCCARDO, Enrique; VILLA, Luisa Lina; SICHERO, LauraIt is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants' functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.
- Prevalence of oral HPV infection in unvaccinated young adults in Brazil(2021) BIDINOTTO, Augusto Bacelo; KOPS, Natalia Luiza; BESSEL, Marina; MARANHAO, Ana Goretti Kalume; MORENO, Flavia; PEREIRA, Gerson Fernando Mendes; VILLA, Luisa Lina; WENDLAND, Eliana MarciaObjectives: This study aimed to report the national prevalence of oral HPV infection among unvaccinated women and men aged 16-25 years who utilized the public primary care services. Methods: POP-Brazil is a cross-sectional, multicentric, nationwide survey conducted between September 2016 and November 2017. Recruitment was based in 119 public primary care practices in 26 state capitals and the Federal District of Brazil. Trained health professionals conducted face-to-face interviews. Oral samples were collected with mouthwash and gargle cycles. Genotyping was performed using the Roche PCR-based linear array genotyping test. Sampling weights by sex and age were applied. Results: Valid oral HPV samples were collected from 5071 (96.88%) participants; 4005 women and 1066 men. Mean participant age was 21.63 years. Overall HPV prevalence was 1.69% (n = 73, 95% CI 1.05-2.32). Thirty individuals presented at least one high-risk HPV type [0.57% (95% CI, 0.29-0.85)]. There were no associations between age, sex, sociodemographic characteristics, drug use or sexual behavior and oral HPV prevalence. Conclusion: The prevalence of oral HPV infection in Brazilian teenagers and young adults is low, with no sociodemographic or behavioral correlates.
- Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study(2021) BETTAMPADI, Deepti; SIRAK, Bradley A.; ABRAHAMSEN, Martha E.; REICH, Richard R.; VILLA, Luisa L.; PONCE, Eduardo Lazcano; GIULIANO, Anna R.Background. Human papillomavirus (HPV)-attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors. Methods. Oral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF 10 PCR-DEIA-LiPA 25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors. Results. Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV infections persisted >= 24 months. Six months' persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months' persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status. Conclusions. Eighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.
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- Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix(2021) BISPO, Saloe; FARIAS, Ticiana D. J.; ARAUJO-SOUZA, Patricia Savio de; CINTRA, Ricardo; SANTOS, Hellen Geremias dos; JORGE, Natasha Andressa Nogueira; CASTRO, Mauro Antonio Alves; WAJNBERG, Gabriel; SCHERER, Nicole de Miranda; GENTA, Maria Luiza Nogueira Dias; CARVALHO, Jesus Paula; VILLA, Luisa Lina; SICHERO, Laura; PASSETTI, FabioSquamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes DSG1-AS1, CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed by miR-96-5p or miR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize LINC02381 might act by decreasing the levels of miR-96-5p and miR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools.
- An Updated Systematic Review of Human Papillomavirus Genotype Distribution by Cervical Disease Grade in Women Living With Human Immunodeficiency Virus Highlights Limited Findings From Latin America(2021) DICKEY, Brittney L.; COGHILL, Anna E.; ELLSWORTH, Grant B.; WILKIN, Timothy J.; VILLA, Luisa L.; GIULIANO, Anna R.Cervical cancer is 5 times more likely among women living with human immunodeficiency virus (WHIV), likely due to higher prevalence of human papillomavirus (HPV). Despite evidence of higher rates with multiple HPV genotypes in WHIV, there are no recommendations for triage by HPV genotyping specific to WHIV. In Latin America/Caribbean rates are high and vary significantly. To guide optimization of HPV-based cervical cancer screening among WHIV in Latin America/Caribbean, review of current literature was completed to assess HPV genotype distribution by cervical disease grade in WHIV in this region; and further expanded globally for comparison across regions. A systematic review of the literature from June 2016 to January 2020 revealed 15 studies reporting human papillomavirus (HPV) genotype distribution by cervical disease state (normal, low-grade disease, high-grade disease, and invasive cervical cancer) across different global regions. Across all studies, there were 6928 WHIV from 4 global regions, 3952 of whom were HPV-positive. Three studies from Latin America/Caribbean (LAC) countries were reviewed, with 1 providing enough detail to describe HPV genotypes by cervical disease grade and identified types 31 and 35 in high-grade cervical lesions. Of the studies included, 4 from Africa and Europe/North America each, and 1 from Asia included data that were able to be summarized. Latin America, a region which experiences high rates of HPV, human immunodeficiency virus (HIV), and cervical disease, had few published studies reporting HPV genotypes by cervical disease grade, with 1 reporting individual HPV genotype and specific cervical disease grade. Identifying HPV types associated with CIN2+ in WHIV in this region has the potential to improve screening and treatment for cervical cancer prevention and should be the focus of future research.
- Relationship between p16 and tumor-infiltrating lymphocytes in Peruvian patients with head and neck cancer(2021) CASTANEDA, C. A.; GARCIA, M. Castillo; BERNABE, L. A.; SANCHEZ, J.; TELLO, K.; ALATRSITA, R.; VILLA, L.; SICHERO, L.; ENCISO, J.; GUERRA, H.
- Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil(2021) KOPS, Natalia Luiza; CAIERAO, Juliana; BESSEL, Marina; HORVATH, Jaqueline Driemeyer Correia; DOMINGUES, Carla Magda; BENZAKEN, Adele Schwartz; VILLA, Luisa Lina; SOUZA, Flavia Moreno Alves de; PEREIRA, Gerson Fernando Mendes; WENDLAND, Eliana MarciaObjectives To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines. Methods This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. Results Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections. Conclusions In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention. Plain Language Summary Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16-25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07-34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.
- Global incidence trends in head and neck cancer for HPV-related and -unrelated subsites: A systematic review of population-based studies(2021) MENEZES, Fabricio dos Santos; FERNANDES, Gisele Aparecida; ANTUNES, Jose Leopoldo Ferreira; VILLA, Luisa Lina; TOPORCOV, Tatiana NatashaIn head and neck cancer (HNC), some subsites are associated with human papillomavirus (HPV) infection, whereas others are unrelated. Although studies have demonstrated the heterogeneity of HPV prevalence worldwide, its impacts on incidence trends in HNC are unknown. This systematic review examined the incidence trends for HPV-related HNC subsites, exploring patterns by geographic region, age group, sex, and race/ ethnicity. We searched for publications on PubMed, Embase, and Scopus. Eligible articles included populationbased studies that analyzed incidence trends for subsites classified as a proxy for HPV infection in HNC (hereafter referred to as HPV-related subsites). We retrieved 3,948 non-duplicate records, of which 31 were eligible articles, representing 18 countries and spanning almost fifty years. Overall, the incidence of HPV-related HNC subsites rose, while most of the HPV-unrelated subsites declined or remained stable. For HPV-related HNC subsites, incidence trends increased regardless of age group, highlighting a distinct global pattern between sexes. Also, similar peaks in increased risk were observed in recent cohorts from both Australia and the United States. There is a dramatic shift in the global trends of HNCs, characterized by the emerging burden in HNC for HPV-related subsites.