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
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- Polymorphism in the promoter region of the Toll-like receptor 9 gene and cervical human papillomavirus infection(2013) OLIVEIRA, Lucas Boeno; LOUVANTO, Karolina; RAMANAKUMAR, Agnihotram V.; FRANCO, Eduardo L.; VILLA, Luisa L.Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TO) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.
- THE AGE-SPECIFIC DISTRIBUTION OF GENITAL HUMAN PAPILLOMAVIRUS (HPV) INFECTION AND HERPES SIMPLEX VIRUS-2 (HSV-2) ANTIBODIES AMONG MEN WITH GENDER-FIXED AND GENDER-FLUID SEXUAL BEHAVIOUR: THE HIM STUDY(2013) NYITRAY, A. G.; ROSS, M. W.; WILKERSON, M.; VILLA, L. L.; ABRAHAMSEN, M.; PAPENFUSS, M.; LAZCANO-PONCE, E.; GIULIANO, A. R.
- Planning cancer control in Latin America and the Caribbean(2013) GOSS, Paul E.; LEE, Brittany L.; BADOVINAC-CRNJEVIC, Tanja; STRASSER-WEIPPL, Kathrin; CHAVARRI-GUERRA, Yanin; LOUIS, Jessica St; VILLARREAL-GARZA, Cynthia; UNGER-SALDANA, Karla; FERREYRA, Mayra; DEBIASI, Marcio; LIEDKE, Pedro E. R.; TOUYA, Diego; WERUTSKY, Gustavo; HIGGINS, Michaela; FAN, Lei; VASCONCELOS, Claudia; CAZAP, Eduardo; VALLEJOS, Carlos; MOHAR, Alejandro; KNAUL, Felicia; ARREOLA, Hector; BATURA, Rekha; LUCIANI, Silvana; SULLIVAN, Richard; FINKELSTEIN, Dianne; SIMON, Sergio; BARRIOS, Carlos; KIGHTLINGER, Rebecca; GELRUD, Andres; BYCHKOVSKY, Vladimir; LOPES, Gilberto; STEFANI, Stephen; BLAYA, Marcelo; SOUZA, Fabiano Hahn; SANTOS, Franklin Santana; KAEMMERER, Alberto; AZAMBUJA, Evandro de; ZORILLA, Andres Felipe Cardona; MURILLO, Raul; JERONIMO, Jose; TSU, Vivien; CARVALHO, Andre; GIL, Carlos Ferreira; STERNBERG, Cinthya; DUENAS-GONZALEZ, Alfonso; SGROI, Dennis; CUELLO, Mauricio; FRESCO, Rodrigo; REIS, Rui Manuel; MASERA, Guiseppe; GABUS, Raul; RIBEIRO, Raul; KNUST, Renata; ISMAEL, Gustavo; ROSENBLATT, Eduardo; ROTH, Berta; VILLA, Luisa; SOLARES, Argelia Lara; LEON, Marta Ximena; TORRES-VIGIL, Isabel; COVARRUBIAS-GOMEZ, Alfredo; HERNANDEZ, Andres; BERTOLINO, Mariela; SCHWARTSMANN, Gilberto; SANTILLANA, Sergio; ESTEVA, Francisco; FEIN, Luis; MANO, Max; GOMEZ, Henry; HURLBERT, Marc; DURSTINE, Alessandra; AZENHA, GustavoNon-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.
- Cutaneous human papillomayirus types detected on the surface of male external genital lesions: A case series within the HPV Infection in Men Study(2013) CAMPBELL, Christine M. Pierce; MESSINA, Jane L.; STOLER, Mark H.; JUKIC, Drazen M.; TOMMASINO, Massimo; GHEIT, Tarik; ROLLISON, Dana E.; SICHERO, Laura; SIRAK, Bradley A.; INGLES, Donna J.; ABRAHAMSEN, Martha; LU, Beibei; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.Background: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta []-HPV in male genital skin or external genital lesions (EGLs) Objectives: To examine cutaneous beta-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. Study design: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Results: beta-HPV DNA was detected on 61.1% of all EGLs, with types 38(16.7%), 5(15.3%), and 12(12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of beta-HPV types detected on condylomas. Most beta-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. Conclusions: EGLs and the normal genital skin of men harbor a large number of beta-HPV types; however, it appears that beta-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.
- Self-collection for high-risk HPV detection in Brazilian women using the caFeHPV (TM) test(2013) LORENZI, Adriana Tarla; FREGNANI, Jose Humberto T. G.; POSSATI-RESENDE, Julio Cesar; NETO, Cristovam Scapulatempo; VILLA, Luisa Lina; LONGATTO-FILHO, AdhemarObjective. Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a new methodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. Methods. Two thousand women aged 18-77 years were enrolled in an opportunistic cervical cancer screening program and were randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV (TM) test was performed on all samples. Pap tests were performed on all women using liquid-based cytology. Results. Positive hr-HPV results were obtained in 12.3% (245/2000) of women; similar rates were observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US + were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. Conclusions. Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings.
- Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study(2013) SICHERO, Laura; CAMPBELL, Christine M. Pierce; FERREIRA, Silvaneide; SOBRINHO, Joao S.; BAGGIO, Maria Luiza; GALAN, Lenice; SILVA, Roberto C.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 alpha-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of alpha-, beta- and gamma-HPV at the male genitals.
- Epidemiologic Approaches to Evaluating the Potential for Human Papillomavirus Type Replacement Postvaccination(2013) TOTA, Joseph E.; RAMANAKUMAR, Agnihotram V.; JIANG, Mengzhu; DILLNER, Joakim; WALTER, Stephen D.; KAUFMAN, Jay S.; COUTLEE, Francois; VILLA, Luisa L.; FRANCO, Eduardo L.Currently, 2 vaccines exist that prevent infection by the genotypes of human papillomavirus (HPV) responsible for approximately 70% of cervical cancer cases worldwide. Although vaccination is expected to reduce the prevalence of these HPV types, there is concern about the effect this could have on the distribution of other oncogenic types. According to basic ecological principles, if competition exists between >= 2 different HPV types for niche occupation during natural infection, elimination of 1 type may lead to an increase in other type(s). Here, we discuss this issue of ""type replacement"" and present different epidemiologic approaches for evaluation of HPV type competition. Briefly, these approaches involve: 1) calculation of the expected frequency of coinfection under independence between HPV types for comparison with observed frequency; 2) construction of hierarchical logistic regression models for each vaccine-targeted type; and 3) construction of Kaplan-Meier curves and Cox models to evaluate sequential acquisition and clearance of HPV types according to baseline HPV status. We also discuss a related issue concerning diagnostic artifacts arising when multiple HPV types are present in specific samples (due to the inability of broad-spectrum assays to detect certain types present in lower concentrations). This may result in an apparent increase in previously undetected types postvaccination.
- Men Who Purchase Sex, Who Are They? An Interurban Comparison(2013) OMPAD, Danielle C.; BELL, David L.; AMESTY, Silvia; NYITRAY, Alan G.; PAPENFUSS, Mary; LAZCANO-PONCE, Eduardo; VILLA, Luisa L.; GIULIANO, Anna R.Most research concerning clients of commercial sex workers (CSWs) relies upon CSW reports of client characteristics and behavior. We describe correlates of ever purchasing sex among 3,829 men from three cities: Sao Paulo, Brazil; Cuernavaca, Mexico; and Tampa, USA. A computer-assisted self-interview collected data on demographics and sexual behavior. There were significant site differences-26.5 % paid for sex in Sao Paulo, 10.4 % in Cuernavaca, and 4.9 % in Tampa. In all cities, men who had sex with men and women (versus sex with women only) were more likely to have ever paid for sex. In Sao Paulo and Cuernavaca, CSW clients were older, had higher educational attainment, and were less likely to be married. In Tampa, older age was associated with being a CSW client but not education and marital status. In Sao Paulo and Cuernavaca, CSW clients had more partners than men who had never paid for sex. In Sao Paulo, CSW clients initiated vaginal sex at an earlier age, while in Cuernavaca they were more likely to self-report a sexually transmitted infection. CSW clients varied with respect to demographics across the three cities while the association between paying for sex and risky sexual behavior seems to be somewhat conserved. These findings suggest that interventions among CSW clients should focus on condom use with commercial and non-commercial partners as these men may be at increased risk for transmitting and acquiring sexually transmitted infections to and from their sex partners. Better understanding of client characteristics is needed for targeting interventions and creating culturally appropriate content.
- Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil(2013) MATOS, Renata Prandini Adum de; SICHERO, Laura; MANSUR, Isabela Mazuco; BONFIM, Caroline Measso do; BITTAR, Cintia; NOGUEIRA, Rodrigo Lacerda; KUEPPER, Daniel Salgado; VALERA, Fabiana Cardoso Pereira; NOGUEIRA, Mauricio Lacerda; VILLA, Luisa Lina; CALMON, Marilia Freitas; RAHAL, PaulaThere are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18.
- Human papillomavirus type 16 viral load measurement as a predictor of infection clearance(2013) TREVISAN, Andrea; SCHLECHT, Nicolas F.; RAMANAKUMAR, Agnihotram V.; VILLA, Luisa L.; FRANCO, Eduardo L.Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman's rank correlation, rho=0.88), but decreased for L1 qRT-PCR versus LS-PCR (rho=0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol.