LAURA CRISTINA SICHERO VETTORAZZO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- 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.
- 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.
- Lack of Association between Human Papillomavirus Types 6 and 11 Genetic Variants and Cervical Abnormalities: The Ludwig-McGill Cohort Study(2019) SICHERO, Laura; EL-ZEIN, Mariam; FERREIRA, Silvaneide; FRANCO, Eduardo L.; VILLA, Luisa L.; BAGGIO, Maria Luiza; GALAN, Lenice; SOBRINHO, Joao Simao; PRADO, Jose Carlos Mann; TERMINI, Lara; COSTA, Maria Cecilia; MIYAMURA, Romulo; TREVISAN, Andrea; THOMANN, Patricia; CANDEIAS, Joao; RAHAL, Paula; RUIZ, Antonio; KAIANO, Jane; SANTOS, Monica; SAVIO, Patricia; MACIAG, Paulo; RABACHINI, Tatiana; EL-ZEIN, Mariam; ROUSSEAU, Marie-Claude; MAHMUD, Salaheddin; SCHLECHT, Nicolas; TROTTIER, Helen; RICHARDSON, Harriet; FERENCZY, Alex; ROHAN, Thomas; CHEVARIE-DAVIS, Myriam; LOUVANTO, Karolina; TOTA, Joseph; SHAW, Eileen; RAMANAKUMAR, Agnihotram; DUARTE, Eliane; KULAGA, Sophie; ROBITAILLE, Juliette; FRANCO, EduardoBackground: Human papillomavirus (HPV) types 6 and 11 are mainly associated with the development of genital warts and recurrent respiratory papillomatosis. We examined intratypic genetic variability of both viral types with the development of cervical cytologic abnormalities in Brazilian women. Methods: We used PCR sequencing to characterize variants of HPVs 6 and/or 11 in cervical swabs from women in the Ludwig-McGill Cohort Study. We used a binomial generalized estimating equations (GEE) model with logit link to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV 6 and 11 variants and cytologic abnormalities. Results: B1 and B3 HPV6 and A2 HPV11 variants were the most common isolates identified. Compared with HPV6-negative women, the ORs among women harboring HPV6 B1 or B3 variants were 6.3 (95% CI, 2.3-17.0) and 2.3 (95% CI, 0.6-9.7) for atypical cells of undetermined significance (ASCUS)/low squamous intraepithelial lesions (LSIL), respectively, and 1.7 (95% CI, 0.6-5.1) and 1.2 (95% CI, 0.3-4.7) for ASCUS/LSIL/high squamous intraepithelial lesions (HSIL). Respective ORs were 5.0 (95% CI, 1.7-14.6) and 2.8 (95% CI, 1.0-8.1) upon comparing women with HPV11 A2 variants to HPV11-negative women. All associations disappeared when adjusting for coinfections with high-risk HPV types. Conclusions: Our data do not support an association between low-risk HPVs 6 and 11 genetic variability and cervical abnormalities. Impact: Risk of cervical cytologic abnormalities is not affected by intratypic polymorphism in HPVs 6 and 11.
- 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.