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
16 resultados
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- Cutaneous human papillomayirus types detected on the surface of male external genital lesions: A case series within the HPV Infection in Men Study(2013) CAMPBELL, Christine M. Pierce; MESSINA, Jane L.; STOLER, Mark H.; JUKIC, Drazen M.; TOMMASINO, Massimo; GHEIT, Tarik; ROLLISON, Dana E.; SICHERO, Laura; SIRAK, Bradley A.; INGLES, Donna J.; ABRAHAMSEN, Martha; LU, Beibei; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.Background: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta []-HPV in male genital skin or external genital lesions (EGLs) Objectives: To examine cutaneous beta-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. Study design: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Results: beta-HPV DNA was detected on 61.1% of all EGLs, with types 38(16.7%), 5(15.3%), and 12(12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of beta-HPV types detected on condylomas. Most beta-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. Conclusions: EGLs and the normal genital skin of men harbor a large number of beta-HPV types; however, it appears that beta-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.
- Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study(2016) CAMPBELL, Christine M. Pierce; GHEIT, Tarik; TOMMASINO, Massimo; LIN, Hui-Yi; TORRES, B. Nelson; MESSINA, Jane L.; STOLER, Mark H.; ROLLISON, Dana E.; SIRAK, Bradley A.; ABRAHAMSEN, Martha; SILVA, Roberto J. Carvalho da; SICHERO, Laura; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.Background: Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. Methods: In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. Results: While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Conclusions: Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. (C) 2016 Published by Elsevier Inc.
- 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.
- 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.
- Human Papillomavirus and Genital Disease in Men: What We Have Learned from the HIM Study(2019) SICHERO, Laura; GIULIANO, Anna R.; VILLA, Luisa LinaIt is currently recognized that in addition to the major impact of human papillomavirus (HPV) infection in females, HPV causes considerable disease in men at the genitals, anal canal, and oropharynx. Specifically, genital HPV infections may progress to genital warts and penile carcinoma. Although studies concerning the natural history of HPV infections and associated neoplasias have mainly focused on women, during the last 2 decades considerable attention has been given in further understanding these infections in men. The HIM (HPV infection in men) Study, the only prospective multi-center study of male HPV natural history, consisted of a large prospective international cohort study in which men from Brazil, the United States, and Mexico were enrolled. The design and protocols of this study allowed unraveling crucial information regarding the relationship between HPV infection and clinical consequences in men, and associated risk factors at each of the anatomic sites where HPV is known to cause cancer in men. (C) 2019 S. Karger AG, Basel
- Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers(2020) MAK, Milena Perez; PASINI, Fatima Solange; DIAO, Lixia; GARCIA, Fabyane O. Teixeira; TAKAHASHI, Tiago Kenji; NAKAZOTO, Denyei; MARTINS, Renata Eiras; ALMEIDA, Cristiane Maria; KULCSAR, Marco Aurelio Vamondes; LAMOUNIER, Valdelania Aparecida; NUNES, Emily Montosa; SOUZA, Isabela Cristina de; GARCIA, Marcio Ricardo Taveira; AMADIO, Alex Vieira; SIQUEIRA, Sheila Aparecida C.; SNITCOVSKY, Igor Moyses Longo; SICHERO, Laura; WANG, Jing; JR, Gilberto de CastroBackground: Cisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers. Methods: This phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated. Results: Given significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival. Conclusions: VPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122).
- 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.
- Beta Human Papillomavirus and Associated Diseases(2019) SICHERO, Laura; ROLLISON, Dana E.; AMORRORTU, Rossybelle P.; TOMMASINO, MassimoThe cutaneous human papillomavirus (HPV), mostly from beta and gamma-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of beta-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis. Likewise, immunosuppressed organ transplant recipients have an increased susceptibility to beta-HPV infections in the skin as well as to cSCC development. Although ultraviolet radiation (UVR) is the main risk factor of cSCC, experimental data points toward beta-HPVs as co-carcinogens, which appear to be required solely at early stages of skin carcinogenesis by facilitating the accumulation of UVR-induced DNA mutations. Several epidemiological studies relying on different biomarkers of beta-HPV infections have also been conducted in immunocompetent individuals to access their association with cSCC development. Additionally, in vivo and in vitro studies are presenting cumulative evidence that E6 and E7 proteins from specific beta-HPVs exhibit transforming activities and may collaborate with different environmental factors in promoting carcinogenesis. Nevertheless, further research is crucial to better understand the pathological implications of the broad distribution of these HPVs. (C) 2019 S. Karger AG, Basel
- HPV-related external genital lesions among men residing in Brazil(2017) SILVA, Roberto Jose Carvalho da; SUDENGA, Staci Lynn; SICHERO, Laura; BAGGIO, Maria Luiza; GALAN, Lenice; CINTRA, Ricardo; TORRES, Benji Nelson; STOLER, Mark; GIULIANO, Anna Regina; VILLA, Luisa LinaThe aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18-73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan-Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with nonHPV lesions. HPV-positive men who developed EGLs were younger (p = 0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV. (C) 2017 Sociedade Brasileira de Infectologia.