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
7 resultados
Resultados de Busca
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- 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.
- 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.
- Epidemiologic Evaluation of Human Papillomavirus Type Competition and the Potential for Type Replacement Post-Vaccination(2016) TOTA, Joseph E.; JIANG, Mengzhu; RAMANAKUMAR, Agnihotram V.; WALTER, Stephen D.; KAUFMAN, Jay S.; COUTLEE, Francois; RICHARDSON, Harriet; BURCHELL, Ann N.; KOUSHIK, Anita; MAYRAND, Marie Helene; VILLA, Luisa L.; FRANCO, Eduardo L.Background Millions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females. Methods Valid HPV DNA typing information was available from five epidemiological studies conducted in Canada and Brazil (n = 14,685; enrollment across studies took place between1993 and 2010), which used similar consensus-primer PCR assays, capable of detecting up to 40 HPV types. A total of 38,088 cervicovaginal specimens were available for inclusion in our analyses evaluating HPV type-type interactions involving vaccine-targeted types (6, 11, 16, and 18), and infection with each of the other HPV types. Results Across the studies, the average age of participants ranged from 21.0 to 43.7 years. HPV16 was the most common type (prevalence range: 1.0% to 13.8%), and in general HPV types were more likely to be detected as part of a multiple infection than as single infections. In our analyses focusing on each of the vaccine-targeted HPV types separately, many significant positive associations were observed (particularly involving HPV16); however, we did not observe any statistically significant negative associations. Conclusions Our findings suggest that natural HPV type competition does not exist, and that type replacement is unlikely to occur in vaccinated populations.
- Determinants of baseline seroreactivity to human papillomavirus type 16 in the Ludwig-McGill cohort study(2014) ARAUJO-SOUZA, Patricia S. de; RAMANAKUMAR, Agnihotram V.; CANDEIAS, Joao M. G.; THOMANN, Patricia; TREVISAN, Andrea; FRANCO, Eduardo L.; VILLA, Luisa L.Background: Immunity plays an important role in controlling human papillomavirus (HPV) infection and associated lesions. Unlike infections caused by other viruses, natural HPV infection does not always result in a protective antibody response. Therefore, HPV antibodies are also considered markers of cumulative exposure. The aim of this study was to identify determinants of HPV16 seroreactivity at enrollment among women from the Ludwig-McGill cohort, a natural history study of HPV infection and risk of cervical neoplasia. Methods: HPV16 serology was assessed by ELISA for L1 and L2 capsid antigens, while HPV typing and viral load measurements were performed by PCR-based methods. The associations were analyzed by unconditional logistic regression. Results: Of 2049 subjects, 425 (20.7%) were strongly seropositive for HPV16. In multivariate analysis, seroreactivity was positively correlated with age, lifetime number of sexual partners, frequency of sex, and HPV16 viral load, and negatively associated with duration of smoking. Conclusions: HPV16 seroreactivity is determined by factors that reflect viral exposure.
- Association Between Human Leukocyte Antigen Polymorphism and Human Papillomavirus Infection in Brazilian Women(2023) ARAUJO-SOUZA, Patricia Savio de; EL-ZEIN, Mariam; BOLPETTI, Aline do N.; MACIAG, Paulo Cesar; RABACHINI, Tatiana; FRANCO, Eduardo L.; VILLA, Luisa L.A prospective study of human papillomavirus infections and risk of cervical neoplasia in Brazilian women found that human leukocyte antigen polymorphisms may influence the natural history of these infections. BackgroundHuman papillomavirus (HPV) infection is a necessary cause for cervical cancer, but a majority of genital HPV infections clear spontaneously. Human leukocyte antigen (HLA) polymorphism influences immune response and genetic susceptibility, and its association with cervical cancer was extensively investigated, but few reports focused on HPV infection.MethodsWe performed molecular typing of HLA-A, HLA-B, HLA-DQB1, and HLA-DRB1 genes as well as of HPV in 1226 women enrolled in the Ludwig-McGill cohort study and investigated the influence on cumulative HPV positivity. HPV types were grouped according to Alphapapillomavirus subgenera that exhibit similar tissue tropism and biological behavior concerning cancer risk. The associations between HLA polymorphisms and HPV infections were estimated using unconditional logistic regression analysis adjusted for age and race.ResultsHLA-B*08 and HLA-DRB1*15:01 were negatively associated with HPV positivity, and similar effects were observed for HPV subgenus 2 only, which includes HPV16. HLA-DRB1*08:07 was associated with overall HPV infection and subgenus 2 positivity. The haplotypes HLA-B*08-DRB1*03:01-DQB1*02:01 and HLA-DRB1*08:07-DQB1*04:02 were negatively and positively associated with cumulative HPV positivity, respectively.ConclusionsOur data suggest that HLA class I and II polymorphism can influence HPV natural infection.
- Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens(2020) TREVISAN, Andrea; CANDEIAS, Joao M. G.; THOMANN, Patricia; VILLA, Luisa L.; FRANCO, Eduardo L.; TROTTIER, HelenIntroduction. Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1-2 years. Although not all infected women develop detectable HPV antibodies, about 60-70% seroconvert and retain their antibodies at low levels. Aim. We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load. Methodology. We used baseline data for women participating in the Ludwig-McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson's r was used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression. Results. Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (r=0.43 and 0.44 for dilutions 1 :10 and 1:50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1: 10 (ROC area=0.73, 95% CI: 0.65-0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species. Conclusion. HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.
- Betapapillomavirus natural history and co-detection with alphapapillomavirus in cervical samples of adult women(2023) MALAGON, Talia; RIBEIRO, Aline Lopes; NUNES, Emily Montosa; GHEIT, Tarik; EL-ZEIN, Mariam; VILLA, Luisa L.; FRANCO, Eduardo L.; SICHERO, LauraHuman papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on their natural history at mucosal sites remains scarce. We examined the risk factors and co-detection patterns of HPVs of the Betapapillomavirus and Alphapapillomavirus genera in cervical samples of the Ludwig-McGill cohort study. We assessed a subset of 505 women from the Ludwig-McGill cohort study from Sao Paulo, Brazil. Cervical samples over the first year of follow-up were tested for DNA of over 40 alphapapillomavirus types and 43 betapapillomavirus types using a type-specific multiplex genotyping polymerase chain reaction assay. We assessed the risk factors for prevalent and incident betapapillomavirus type detection, and whether types were detected more frequently together than expected assuming independence using permutation tests, logistic regression, and Cox regression. We observed significant within-genus clustering but not cross-genus clustering. Multiple betapapillomavirus types were co-detected in the same sample 2.24 (95% confidence interval [CI]: 1.65-3.29) times more frequently than expected. Conversely, co-detections of alphapapillomavirus and betapapillomavirus types in the same sample occurred only 0.64 (95% CI: 0.51-0.83) times as often as expected under independence. In prospective analyses, positivity to one HPV genus was associated with a nonsignificant lower incidence of detection of types in the other genus. Lifetime number of sex partners and new sex partner acquisition were associated with lower risks of prevalent and incident betapapillomavirus detection. Betapapillomaviruses are commonly found in the cervicovaginal tract. Results suggest potentially different mechanisms of transmission for betapapillomavirus genital infections other than vaginal sex.