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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Risk of Human Papillomavirus (HPV) Infection and Cervical Neoplasia after Pregnancy(2015) TROTTIER, Helen; MAYRAND, Marie-Helene; BAGGIO, Maria Luiza; GALAN, Lenice; FERENCZY, Alex; VILLA, Luisa L.; FRANCO, Eduardo L.Background: Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy. Methods: We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993-97 and followed for up to 10 years. Cellular specimens were collected every 4-6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding. Results: We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders. Conclusions: No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results.
- Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection(2022) MORALES, Julia Andrade Pessoa; MARCONI, Camila; EL-ZEIN, Mariam; RAVEL, Jacques; PINTO, Gabriel Victor da Silva; SILVEIRA, Rosana; LIMA, Moises Diogo de; CARVALHO, Newton Sergio de; ALVES, Rosane Ribeiro Figueiredo; PARADA, Cristina Maria Garcia de Lima; LEITE, Sandra Helena Morais; VILLA, Luisa L.; FRANCO, Eduardo L.; SILVA, Marcia Guimaraes daBackground Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. Methods We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). Results Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (P = .0163). Conclusions The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification. This cross-sectional study demonstrated a strong correlation between vaginal microbiome components and cervical high-risk HPV positivity.
- Cervical Infection With Vaccine-Associated Human Papillomavirus (HPV) Genotypes as a Predictor of Acquisition and Clearance of Other HPV Infections(2016) TOTA, Joseph E.; RAMANAKUMAR, Agnihotram V.; VILLA, Luisa L.; RICHARDSON, Harriet; BURCHELL, Ann N.; COUTLEE, Francois; FRANCO, Eduardo L.Background. Recent birth cohorts vaccinated against human papillomavirus (HPV) may be protected against up to 4 genotypes (HPV-6, -11, -16, and -18). If natural competition exists between these and other HPV types, then the prevalence of other types may increase after vaccination. Methods.aEuro integral Cohort information from 3 studies was used to compare acquisition and clearance of 30 different HPV types (individually and grouped by species), according to infection status with vaccine-targeted types at baseline and the time of the index infection, respectively. Hazard ratios (HRs) were adjusted for predictors of multiple-type infection. Results.aEuro integral Among 3200 females across all studies, 857 were infected with HPV at baseline, and 994 acquired new infections during follow-up. Females infected with HPV-16 were at higher risk of acquiring other alpha-9 HPV types (HR, 1.9; 95% confidence interval [CI], 1.2-3.0) but at similar risk of clearing existing alpha-9 HPV infections (HR, 0.9; 95% CI, .7-1.3). Females infected with vaccine-targeted types were generally at higher risk of acquiring additional types (HRs, > 1.0) and at equal risk of clearing existing infections. Accounting for multiple comparisons, none of the HRs of < 1.0 or > 1.0 were statistically significant in our analyses of acquisition or clearance. Conclusions.aEuro integral Vaccine-targeted HPV types do not appear to compete with other types, suggesting that HPV type replacement is unlikely to occur.
- 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.
- Human Papillomavirus Intermittence and Risk Factors Associated With First Detections and Redetections in the Ludwig-McGill Cohort Study of Adult Women(2023) MALAGON, Talia; TROTTIER, Helen; EL-ZEIN, Mariam; VILLA, Luisa L.; FRANCO, Eduardo L.; PAULO, SaoBackground We assessed the incidence and risk factors for first detection and redetection with the same human papillomavirus (HPV) genotype, and prevalence of cytological lesions during HPV redetections. Methods The Ludwig-McGill cohort study followed women aged 18-60 years from Sao Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after 1 or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. Results In total, 2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 6.6% at 1 year and 14.8% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90; 95% confidence interval [CI], .54-1.47 for >= 45 years vs < 25 years) nor new sexual partner acquisition (aHR 0.98; 95% CI, .70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). Conclusions Our findings suggest many HPV redetections were likely reactivations of latent recurring infections. Incidence of redetection with the same human papillomavirus genotype was found to be substantially higher than incidence of first detection. Redetections were not associated with new sexual partners. This suggests many human papillomavirus detections could be recurring latent infections.
- 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.