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
- E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes(2021) NUNES, Emily Montosa; TALPE-NUNES, Valeria; SOBRINHO, Joao Simao; FERREIRA, Silvaneide; LINO, Vanesca de Souza; TERMINI, Lara; SILVA, Gabriela Avila Fernandes; BOCCARDO, Enrique; VILLA, Luisa Lina; SICHERO, LauraIt is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants' functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.
- 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.
- Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16(INK4a) status(2022) SICHERO, Laura; TAGLIABUE, Marta; MOTA, Giana; FERREIRA, Silvaneide; NUNES, Rafaella A. L.; CASTANEDA, Carlos Arturo; CASTILLO, Miluska; CORREA, Rita Mariel; PERDOMO, Sandra; RODRIGUEZ-URREGO, Paula A.; MATOS, Leandro Luongo; MOHSSEN, Ansarin; GHEIT, Tarik; TOMMASINO, Massimo; CHIOCCA, Susanna; VILLA, Luisa LinaBackground Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16(INK4a) in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. Methods HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16(INK4a) immunohistochemistry. Results HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16(INK4a) positivity were observed among HPV positive OPC/OCC cases compared to LC cases. Conclusions Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.
conferenceObject Cytokine expression profile in keratinocytes transduced with HPV oncogenes(2018) NUNES, Rafaella Almeida Lima; SILVA, Gabriela Avila Fernandes; FERREIRA, Silvaneide Aparecida; SICHERO, Laura; VILLA, Luisa Lina; BOCCARDO, Enrique; TERMINI, Lara- High genital prevalence of cutaneous human papillomavirus DNA on male genital skin: the HPV Infection in Men Study(2014) SICHERO, Laura; CAMPBELL, Christine M. Pierce; FULP, William; FERREIRA, Silvaneide; SOBRINHO, Joao S.; BAGGIO, Maria Luiza; GALAN, Lenice; SILVA, Roberto C.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.Background: The genital skin of males hosts a diversity of HPV genotypes and uncharacterized HPV genotypes. Previously we demonstrated that a specific viral genotype was not identified in 14% of all genital specimens (i.e., HPV unclassified specimens) using the Roche Linear Array method. Our goal was to identify and assess the prevalence of individual HPV types among genital HPV unclassified specimens collected in the HIM Study population, at enrollment, and examine associations with socio-demographic and behavioral characteristics. Methods: Genital skin specimens of men that were considered unclassified (HPV PCR positive, no genotype specified) at enrollment were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. PGMY/GP+ negative specimens were further analyzed using FAP primers. HPV type classification was conducted through comparisons with sequences in the GenBank database. Results: Readable nucleotide sequences were generated for the majority of previously unclassified specimens (66%), including both characterized (77%) and yet uncharacterized (23%) HPV types. Of the characterized HPV types, most (73%) were Beta [beta]-HPVs, primarily from beta-1 and beta-2 species, followed by Alpha [alpha]-HPVs (20%). Smokers (current and former) were significantly more likely to have an alpha-HPV infection, compared with any other genus; no other factors were associated with specific HPV genera or specific beta-HPV species. Conclusions: Male genital skin harbor a large number of beta-HPV types. Knowledge concerning the prevalence of the diverse HPV types in the men genital is important to better understand the transmission of these viruses.
- HPV-11 variability, persistence and progression to genital warts in men: the HIM study(2017) FLORES-DIAZ, Ema; SEREDAY, Karen A.; FERREIRA, Silvaneide; SIRAK, Bradley; SOBRINHO, Joao Simao; BAGGIO, Maria Luiza; GALAN, Lenice; SILVA, Roberto C.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.; SICHERO, LauraHPV-11 and HPV-6 are the etiological agents of about 90% of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.
- 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.
- Diversity of human papillomavirus in the anal canal of men: the HIM Study(2015) SICHERO, L.; NYITRAY, A. G.; NUNES, E. M.; NEPAL, B.; FERREIRA, S.; SOBRINHO, J. S.; BAGGIO, M. L.; GALAN, L.; SILVA, R. C.; LAZCANO-PONCE, E.; GIULIANO, A. R.; VILLA, L. L.Human papillomavirus (HPV) infections are associated with the development of anogenital lesions in men. There are no reports describing the distribution of non-alpha HPV types in the anal canal of a sexually diverse group of men. The HPV Infection in Men (HIM) Study is a multicentre study on the natural history of HPV infection in Brazil, Mexico, and the USA. At baseline, 12% of anal canal PCR HPV-positive specimens were not typed by the Roche Linear Array, and were considered to be unclassified. Our goals were to characterize HPVs among these unclassified specimens at baseline, and to assess associations with participant socio-demographic and behavioural characteristics. Unclassified HPVs were typed by sequencing of amplified PGMY09/11 products or cloning of PGMY/GP + nested amplicons followed by sequencing. Further analysis was conducted with FAP primers. Of men with unclassified HPV in the anal canal, most (89.1%) were men who have sex with women. Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. Eighteen, 26 and three different alpha-HPV, beta-HPV and gamma-HPV types were detected, respectively. alpha-HPVs were more commonly detected among young men (18-30 years) than among older men (45-70 years), whereas beta-HPVs were more frequent among mid-adult men (31-44 years). beta-HPVs were more common among heterosexual men (85.0%) than among non-heterosexual Men. All beta-HPVs detected among non-heterosexual men were beta 2-HPV types. The high prevalence of beta-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile anal intercourse. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases.
- Role of epstein-barr virus in the severity of recurrent respiratory papillomatosis(2020) COSTA, Victor; EL-ACHKAR, Vivian Narana; BARROS, Patricia Pimentel de; LEON, Jorge Esquiche; RIBEIRO-SILVA, Alfredo; CARLOS, Roman; PIGNATARI, Shirley Shizue Nagata; FERREIRA, Silvaneide; MELLO, Barbara Pereira; SICHERO, Laura; VILLA, Luisa Lina; KAMINAGAKURA, EstelaObjective The objective was to investigate the prevalence of the Epstein-Barr virus (EBV) and its association with human papilloma virus (HPV) detection, clinicopathological features, and the severity of recurrent respiratory papillomatosis (RRP). Methods Cases of juvenile recurrent respiratory papillomatosis (JRRP) (n = 36) and adult recurrent respiratory papillomatosis (ARRP) (n = 44) were collected retrospectively and subdivided into low- and high-risk severity groups based on the Derkay score. We performed HPV detection and genotyping using a reverse hybridization protocol and investigated the presence of EBV by polymerase chain reaction (PCR) and in situ hybridization. CD21 levels were accessed by immunohistochemistry. Results All samples were HPV-positive, including 49 cases of HPV 6, 26 cases of HPV 11, four cases of HPV 6 and 11 coinfections, and one case of HPV 16. EBV-DNA was detected in nine samples by PCR, although none of the cases were positive by means of in situ hybridization. CD21 immunoexpression was not statistically associated with any of the variables analyzed. HPV 6 detection was significantly higher in ARRP cases (P = 0.03), whereas HPV 11 was more prevalent in JRRP cases (P = 0.02) and was even more prevalent in JRRP cases of greater severity (Derkay laryngoscopic scale >= 20) (P = 0.04). Conclusion The presence of EBV does not seem to play an important role in the progression/severity of RRP. Level of Evidence 4 Laryngoscope, 2019
Prevalence and persistence of HPV-16 molecular variants in the anal canal of men: The HIM study
(2022) GONCALVES, Milena Giulia; FERREIRA, Matthew Thomas; LOPEZ, Rossana Veronica Mendoza; FERREIRA, Silvaneide; SIRAK, Bradley; BAGGIO, Maria Luiza; LAZCANO-PONCE, Eduardo; NYITRAY, Alan G.; GIULIANO, Anna R.; VILLA, Luisa L.; SICHERO, LauraBackground: HPV-16 causes approximately 90% of anal canal (AC) cancers worldwide. This study aimed to evaluate the prevalence and persistence of HPV-16 genetic variants in the AC of men from three different countries (Brazil, Mexico and United States) and to further identify sociodemographic and behavioral factors associated with these infections.& nbsp;Methods: Participants from the multinational prospective HPV Infection in Men (HIM) Study who had at least one HPV-16 positive AC swab were included. Characterization into HPV-16 genetic variants was successfully performed by PCR-sequencing in 95.6% (217/227) samples and these were classified into HPV-16 lineages and sublineages.& nbsp;Results: We observed higher prevalence of lineage A variants, mainly from A1 sublineage, in all countries. Non-A lineage variants were mostly detected in men from Brazil, where higher diversity of sublineage variants was detected during follow-up. Compare to men detected with Non-A HPV-16 lineage variants, men infected with lineage A reported a higher lifetime number of female sexual partners. Finally, a significantly higher prevalence of Non-A lineage variants was observed among men who have sex with men (MSM) with a transient HPV-16 AC infection (p = 0.033), but no significant differences regarding variants lineages and persistence status were observed when stratified by country, self-reported ethnicity or age.& nbsp;Conclusions: Our data extend previous reports which indicate that globally HPV-16 variants are unevenly distributed, and contribute further to studies of the natural history of AC HPV infections in men.