Laura Sichero

• PhD, Prof
• Group Leader at Instituto do Câncer do Estado de São Paulo

Oral HPV DNA and circulating tumor (ct) HPV DNA in plasma were evaluated as potential biomarkers for HPV‐associated head and neck cancer (HNC). Samples from HNC patients ( n = 132), including 23 oropharyngeal cancers (OPC), and non‐HNC controls ( n = 10) were analyzed. HPV status was determined using a multiplex bead‐based test (E7‐MPG) applied to...

Objective: This study assesses the associations between dendritic cells, HPV 6 and 11, and Recurrent Respiratory Papillomatosis (RRP) aggressiveness. Methods: The Derkay score was calculated using information obtained from the medical records. Biopsies from 36 patients with juvenile RRP (JRRP) and 43 adult RRP (ARRP) patients were analyzed under li...

Head and neck squamous cell carcinoma (SCC) predisposing factors include smoking and alcohol consumption. However, other agents have been investigated, including viruses. We aimed to investigate the presence of DNA of four different types of human polyomavirus (HPyV) in the oral cavity and oropharyngeal SCC samples from an oncology center in Brazil...

High-risk human papillomavirus (HPV) causes almost all cervical cancer, and HPV-18 is the second most prevalent type. The HPV life cycle is intimately associated with the epithelial differentiation program, and the repertoire of cellular transcription factors (TFs) has a crucial role in coordinating viral gene expression across epithelial layers. W...

Human 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...

Background : Human papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on its 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 c...

Background: Human papillomavirus 16 (HPV-16) non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. Methods:...

Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study...

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained...

Background : 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....

Background Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16INK4a 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 under...

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 clinic...

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expr...

It 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 cell...

Squamous 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 c...

Background The prevalence of Human Papillomavirus type 16 (HPV-16) variants in men and the association with tumor development has not been fully investigated. We estimated the prevalence of genital, anal, and oral HPV-16 infections in men through a systematic review and meta-analysis. Methods Seven databases were searched and included studies that...

Background: 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 biom...

Human papillomavirus (HPV) types 6 and 11 are the etiological agents of recurrent respiratory papillomatosis (RRP). We examined the prevalence and distribution of HPVs 6 and 11 genetic variants in juvenile onset (JORRP) and adult onset (AORRP) laryngeal papillomas. Cases of JORRP and AORRP were collected, retrospectively. HPV detection and genotypi...

Objective: The aim of this study was to perform an epidemiologic, clinical, microscopic, immunohistochemical, and human papillomavirus (HPV) genotypical characterization of laryngeal papillomatosis (LP) and associate its results to the Derkay anatomic score. Study Design: A total of 36 samples of the juvenile group (JLP) and 56 samples of the adult...

Background Chagasic megaesophagus (clinical manifestation of chagasic disease) has been reported as an etiological factor for squamous cell carcinoma of the esophagus, as well as the presence of human papillomavirus (HPV). Objective We accessed the prevalence of HPV DNA in a series of squamous cell carcinomas of the esophagus associated or not with...

Background: Chagasic megaesophagus (clinical manifestation of chagasic disease) has been reported as an etiological factor for squamous cell carcinoma of the esophagus, as well as the presence of human papillomavirus (HPV). Objective: We accessed the prevalence of HPV DNA in a series of squamous cell carcinomas of the esophagus associated or not wi...

Our aim was to review the major contributions of studies conducted in different Latin American (LA) countries to the field of human papillomavirus (HPV) epidemiology, natural history, risk of disease, and prevention strategies, mainly in the uterine cervix. Although cytological screening is established in several countries in LA, incidence and mort...

BACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins E5, E6 and E7 which have a high transformation potential in culture cells when transduced together. In the present study we analyzed how these on...

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by P...

Objective: 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 recurren...

The expression profile of angiogenesis associated proteins was assessed in patients with locally advanced cervical cancer included in a prospective, randomized phase II study. The majority of patients had squamous cell carcinoma (87.8%). Group A individuals were treated with neoadjuvant chemotherapy (cisplatin and gemcitabine) (NAC), followed by ch...

Objectives: Genotyping HPV from samples tested positive to careHPV™ assay in rural and remote areas of Brazilian territory. Methods: A total of 5,079 women were enrolled in an opportunistic screening from the Barretos Cancer Hospital, through mobile units or ambulatory unit. All careHPV™ hr-HPV positive samples were tested by a Luminex-based pro...

Objectives The main aim of this work is to study how E5, E6 and E7 oncogenes of human papillomaviruses type 18 could cooperate among each other to boost key cancer cell features such as uncontrolled cell proliferation, enhanced migration capacity, invasion, and how this relates with oxidative stress. Methods We generated three HaCaT cell lines, th...

Background: The pathogenesis of lung cancer is triggered by a combination of genetic and environmental factors, being the tobacco smoke the most important risk factor. Nevertheless, the incidence of lung cancer in non-smokers is gradually increasing, which demands the search for different other etiological factors such as occupational exposure, pr...

Actinic cheilitis (AC) is considered a precancerous lesion of the lip.1 Renal transplant recipients (RTR) have a higher susceptibility to human papillomavirus (HPV) infections and lip squamous cell carcinoma (SCC). 2 Over 200 HPV types were described and most cluster within the α‐, β‐ and γ‐HPV genera. 3 Merkel Cell Polyomavirus (MCPyV) and several...

The roles of E6 and E7 oncoproteins of Human Papillomavirus type 16 (HPV-16) in the progression of immortalized epithelial cells to invasive tumors are not fully understood. Here, we establish a novel link between E6 and E7 of two molecular variants of HPV-16 (AA and E-350G), and c-MYC, regarding the cooperation in promoting malignant transformatio...

Background: 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 varian...

It 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 infect...

The cutaneous human papillomavirus (HPV), mostly from β- and γ-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of β-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis....

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 an...

Cutaneous human papillomaviruses (HPVs) include β- and γ-HPVs, in addition to a small fraction of α-HPVs. β-HPVs were first isolated from patients with the rare genetic disorder Epidermodysplasia verruciformis, and they are associated with the development of nonmelanoma skin cancer at sun-exposed skin sites in these individuals. Organ transplant re...

Background Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-...

We evaluated the concordance between β-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for...

Methods: Invited patients signed the informed consent form, and interviews were conducted in order to obtain information about sociodemographic and lifestyle behavior. During endoscopy, esophageal biopsies were collected from case and controls. Multiplex polymerase chain reaction genotyping was conducted on endoscopic biopsies to identify HPV type...

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 ana...

e17546 Background: Cisplatin-based chemoradiation (CRT) offers LA HNSCC pts a high local control rate, however, relapses are frequent. Here we evaluated if epigenetic regulation by VA, a histone deacetylase inhibitor (HDACi), combined with CRT in LA HNSCC improves response rate (RR). Methods: Patients with unresectable oropharynx (OP) and oral cavi...

GOAL: To investigate the HPV prevalence and characterize the expression of potential molecular surrogate markers of HPV infection in esophageal squamous cell carcinoma. MATERIALS AND METHODS: The prevalence of HPV in individuals with and without esophageal cancer (EC) was determined by using multiplex PCR; p16 and p53 protein levels were assessed b...

Background: Alpha-human papillomavirus (α-HPV) play a causal role in cervical cancer but little is known about the epidemiology of genital Beta-HPV infection. Methods: We used Luminex and polymerase chain reaction (PCR) hybridization to detect β- and α-HPVs prevalence at enrolment and 12-months follow-up in cervical samples from 505 women enroll...

The 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 Infectio...

Background: HPV-6 and 11 are the etiological agents of approximately 90% genital warts (GWs). The impact of HPV-6 genetic heterogeneity on persistence and progression to GWs remains undetermined. Methods: HPV Infection in Men (HIM) study participants who had HPV-6 genital swabs and/or GWs preceded by a viable normal genital swab were analyzed. V...

Background High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellul...

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), exfoliat...

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...

Our goal was to describe prevalence of β-HPVs at three anatomic sites among 717 men from Brazil, Mexico and US enrolled in the HPV Infection in Men (HIM) Study. β-HPVs were genotyped using Luminex technology. Overall, 77.7%, 54.3% and 29.3% men were positive for any β-HPV at the genitals, anal canal, and oral cavity, respectively. Men from US and B...

Background Human papillomavirus (HPV) prevalence in head and neck squamous cell carcinomas (HNSCC) diverges geographically. The reliability of using p16INK4a expression as a marker of viral infection is controversial in HNSCC. We evaluated HPV types and HPV-16 variants prevalence, and p16INK4a expression in HNSCC specimens provided by two different...

Asian-American (AA) HPV-16 variants are associated with higher risk of cancer. Abnormal activation of intracellular signaling play a critical role in cancer development and progression. Our aim was to elucidate mechanisms underlying the higher oncogenic potential attributed to AA variant. We evaluated activation of MAPK and PI3K/AKT pathways in pri...

A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription f...

Human papillomavirus (HPV) infections are associated with the development of anogenital lesions in men. There are no reports describing the distribution of non-α 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 t...

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 type...

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 [β]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES: To examine cutaneous β-HPV types detected on the surface of EGLs in men and describe t...

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 sequenc...

Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the developmen...

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 nu...

About 15% of all human cancers are caused by viruses; human papillomaviruses (HPV) only are responsible for at least 5% of tumors worldwide. All cervical cancers can be linked to high-risk HPV infections which accounts for about 10% of female cancers in developing countries. Moreover a significant proportion of cancers arising in other anatomical l...

We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes a...

Background: The long control region (LCR) of human papillomavirus (HPV) regulates early gene transcription by interaction with several viral and cellular transcription factors (TFs). Methods: To identify novel TFs that could influence early expression of HPV type 18 (HPV-18) and HPV type 16 (HPV-16), a high-throughput transfection array was used...

Early promoter activity of HPV-58 molecular variants isolated from high-grade cervical lesions in Brazil was compared. Luciferase reporter assays were conducted in C33 cells transfected with the complete long control region of 3 molecular variants of HPV-58 as well as HPV-58, -18 or -16 prototypes. The HPV-58 prototype and Bsb-329 and Bsb-367 varia...

Human papillomavirus (HPV) infection is linked to the development of cervical cancer, and several cofactors contribute to the risk of disease. Research on the intratypic variability of HPVs has defined variants that are associated with persistent infections and are potentially more oncogenic, translating to a higher risk of malignant disease. The g...

More than 100 HPV types have been described, 13 of which are classified as high-risk due to their association with the development of cervical cancer. The intratype genomic diversity of HPV-16 and -18 has been studied extensively, while little data have been generated for other less common high-risk types. The present study explores the nucleotide...

Several studies indicate that molecular variants of HPV-16 have different geographic distribution and risk associated with persistent infection and development of high-grade cervical lesions. In the present study, the frequency of HPV-16 variants was determined in 81 biopsies from women with cervical intraepithelial neoplasia grade III or invasive...

The intratypic variability of HPVs 16 and 18 has been extensively studied and has been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Infections by non-European variants of HPVs 16 and 18 are associated with an increased risk for the development of hig...

Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also b...

Association between non-European variants of human papillomavirus (HPV) type 16 (HPV-16) and HPV-18 and cervical lesions has been suggested. To compare the P105 promoter activity among 6 HPV-18 variants, their complete long control regions (LCRs), as well as that of HeLa cells, were cloned upstream of the luciferase gene and transiently transfected...

Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical...

Human Papillomaviruses (HPVs) are etiologically associated to cervical carcinoma. In order to evaluate HPV infection and its relationship with the high frequency of this neoplasia in Quechua women from Jujuy (Argentina), 271 cervical samples from preneoplastic and neoplastic lesions (biopsies) and normal controls (cytologies) were studied. Detectio...

In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of...

We report on a 15-year-old girl with mental retardation, obesity, short stature and minor anomalies. She had 47 chromosomes with a minute extra ring which was identified by FISH to be derived from chromosome 17.

O principal fator etiológico da neoflasia do colo do útero é a infecção por HPVs (papilomavírus humano) de alto risco oncogênico, principalmente HPVs 16 e 18. A variabilidade intra-típica de ambos tipos virais tem sido extensivamente estudada. A análise da diversidade genética de isolados oriundos de diferentes regiões dos cinco continentes permiti...