LAURA CRISTINA SICHERO VETTORAZZO

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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

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  • article 38 Citação(ões) na Scopus
    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.
  • article 8 Citação(ões) na Scopus
    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.
  • article 34 Citação(ões) na Scopus
    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.
  • article 15 Citação(ões) na Scopus
    Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil
    (2013) MATOS, Renata Prandini Adum de; SICHERO, Laura; MANSUR, Isabela Mazuco; BONFIM, Caroline Measso do; BITTAR, Cintia; NOGUEIRA, Rodrigo Lacerda; KUEPPER, Daniel Salgado; VALERA, Fabiana Cardoso Pereira; NOGUEIRA, Mauricio Lacerda; VILLA, Luisa Lina; CALMON, Marilia Freitas; RAHAL, Paula
    There are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18.
  • article 3 Citação(ões) na Scopus
    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 Lina
    Background 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.
  • article 11 Citação(ões) na Scopus
    HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines
    (2016) CALMON, Marilia Freitas; SICHERO, Laura; BOCCARDO, Enrique; VILLA, Luisa Lina; RAHAL, Paula
    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and 03 cells co-transduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis.
  • article 1 Citação(ões) na Scopus
    Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma
    (2022) MUNARI, F. F.; SICHERO, L.; CARLONI, A. C.; LACERDA, C. F.; NUNES, E. M.; OLIVEIRA, A. T. T. De; SCAPULATEMPO-NETO, C.; SILVA, S. R. M. Da; CREMA, E.; ADAD, S. J.; RODRIGUES, M. A. M.; HENRY, M. A. C. A.; GUIMARãES, D. P.; REIS, R. M.; VILLA, L. L.; LONGATTO-FILHO, A.
    Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
  • article 11 Citação(ões) na Scopus
    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, Laura
    HPV-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.
  • article 11 Citação(ões) na Scopus
    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.
  • article 17 Citação(ões) na Scopus
    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.