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
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- 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.
- 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.
- Cervical Infection with Cutaneous Beta and Mucosal Alpha Papillomaviruses(2017) SICHERO, Laura; EL-ZEIN, Mariam; NUNES, Emily M.; FERREIRA, Silvaneide; FRANCO, Eduardo L.; VILLA, Luisa L.Background: Alpha-human papillomavirus (alpha-HPV) plays a causal role in cervical cancer, but little is known about the epidemiology of genital Beta-human papillomavirus (beta-HPV) infection. Methods: We used Luminex and PCR hybridization to detect band alpha-HPVs prevalence at enrollment and 12-month follow-up in cervical samples from 505 women enrolled in the Ludwig-McGill cohort study. We compared epidemiologic correlates of both band alpha-HPVs and compared genotypes between these genera with respect to co-occurrence and association with cervical cytologic abnormalities. Results: Infection with beta-HPV types was more prevalent than that with alpha-HPV types at both visits (cumulative prevalences: 27.3% vs. 21.6%, respectively, P = 0.034). beta-HPVs were mostly transient; however, only 1.98% women retained their original positivity at 12 months, whereas persistence was higher for alpha-HPVs (5.15%; P = 0.007). Age, parity, and sexual activity variables were predictors of alpha-HPV but not of beta-HPV alpha-and beta-HPV types occurred independently. Increased risk of cervical abnormalities was restricted to women infected with alpha-9 or alpha-6 HPV types. We found no epidemiologic correlates for beta-HPV infections. Conclusions: Detection of beta-HPV types in the cervix tends to occur as random and transient episodes not explained via the sexual-transmission correlates that characterize infections by alpha-HPVs. Impact: Although it is plausible that beta-HPVs may play a direct or indirect carcinogenic role, the lack of epidemiologic correlates for detection episodes of these viruses and lack of association with cervical lesions speak against their ancillary role as sexually transmitted agents in cervical carcinogenesis. (C) 2017 AACR.
- Evaluation of Human Papillomavirus Type Replacement Postvaccination Must Account for Diagnostic Artifacts: Masking of HPV52 by HPV16 in Anogenital Specimens(2015) TOTA, Joseph E.; RAMANAKUMAR, Agnihotram V.; VILLA, Luisa L.; RICHARDSON, Harriet; BURCHELL, Ann N.; KOUSHIK, Anita; MAYRAND, Marie-Helene; COUTLEE, Francois; FRANCO, Eduardo L.It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine-targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent postvaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in coinfected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously ""masked"" types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16(+)/study). Multivariate logistic regression, with adjustment for age and number of sexual partners, was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n = 1,196), the presence of HPV16 was positively associated with HPV52 detection [adjusted OR, 1.47; 95% confidence interval (CI), 0.76-2.82]. In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV-infected males (HIPVIRG study; adjusted OR, 3.82; 95% CI, 1.19-12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend = 0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed. (C) 2014 AACR.
- Reproductive and genital health and risk of cervical human papillomavirus infection: results from the Ludwig-McGill cohort study(2016) SHAW, Eileen; RAMANAKUMAR, Agnihotram V.; EL-ZEIN, Mariam; SILVA, Flavia R.; GALAN, Lenice; BAGGIO, Maria L.; VILLA, Luisa L.; FRANCO, Eduardo L.Background: There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection. Methods: We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95 % confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections. Results: Lifetime (Subgenus 3 OR = 2.00, CI: 1.23-3.24) and current (Subgenus 3 OR = 2.00, CI: 1.15-3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22-3.16, Subgenus 2 OR = 1.34, CI: 1.00-1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30-0.75, Subgenus 2 OR = 0.78, CI: 0.62-0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection. Conclusions: Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed.
- 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.