TONI RICARDO MARTINS
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Critical Analyses of the Introduction of Liquid-Based Cytology in a Public Health Service of the State of Sao Paulo, Brazil(2015) LONGATTO-FILHO, Adhemar; LEVI, Jose Eduardo; MARTINS, Toni Ricardo; COHEN, Diane; CURY, Lise; VILLA, Luisa Lina; ELUF-NETO, JoseObjective: The aim of this study was to compare the performance of the current conventional Pap smear with liquidbased cytology (LBC) preparations. Study Design: Women routinely undergoing their cytopathological and histopathological examinations at Fundacao Oncocentro de Sao Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of Sao Paulo with similar sociodemographic characteristics. Results: A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells -cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the twomethods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of highgrade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). Conclusions : LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs. (C) 2015 S. Karger AG, Basel
- Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA(2015) VEO, Carlos A. R.; SAAD, Sarhan S.; FREGNANI, Jose Humberto T. G.; SCAPULATEMPO-NETO, Cristovam; TSUNODA, Audrey Tieko; RESENDE, Julio Cesar Possati; LORENZI, Adriana Tarla; MAFRA, Allini; CINTI, Claudia; COTRIM, Ismael Dale; ROSA, Luciana Albina Reis; OLIVEIRA, Cristina Mendes de; MARTINS, Toni Ricardo; CENTRONE, Cristiane; LEVI, Jose Eduardo; LONGATTO-FILHO, AdhemarHigh-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.
- PCR-RFLP assay as an option for primary HPV test(2018) GOLFETTO, L.; ALVES, E. V.; MARTINS, T. R.; SINCERO, T. C. M.; CASTRO, J. B. S.; DANNEBROCK, C.; OLIVEIRA, J. G.; LEVI, J. E.; ONOFRE, A. S. C.; BAZZO, M. L.Persistent human papillomavirus (HPV) infection is an essential factor of cervical cancer. This study evaluated the analytical performance of restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) assay compared to PapilloChecks (R) microarray to identify human papilloma virus (HPV) in cervical cells. Three hundred and twenty-five women were analyzed. One sample was used for conventional cytology and another sample was collected using BD SurePath (TM) kit for HPV tests. Eighty samples (24.6%) were positive for HPV gene by PCR-Multiplex and were then submitted to PCR-RFLP and PapilloChecks (R) microarray. There was a genotyping agreement in 71.25% (57/80) on at least one HPV type between PCRRFLP and PapilloChecks (R) microarray. In 22 samples (27.5%), the results were discordant and those samples were additionally analyzed by DNA sequencing. HPV 16 was the most prevalent HPV type found in both methods, followed by HPVs 53, 68, 18, 39, and 66 using PCR-RFLP analysis, and HPVs 39, 53, 68, 56, 31, and 66 using PapilloChecks (R) microarray. In the present study, a perfect agreement using Cohen's kappa (kappa) was found in HPV 33 and 58 (kappa=1), very good for HPV 51, and good for types 16, 18, 53, 59, 66, 68, 70, and 73. PCR-RFLP analysis identified only 25% (20/80) HPV coinfection, and PapilloChecks (R) microarray found 62.5% (50/80). Our Cohen's kappa results indicate that our in-house HPV genotyping testing (PCR-RFLP analysis) could be applied as a primary HPV test screening, especially in low income countries. If multiple HPV types are found in this primary test, a more descriptive test, such as PapilloChecks (R) microarray, could be performed.
- High-Risk HPV Testing in Primary Screening for Cervical Cancer in the Public Health System, Sao Paulo, Brazil(2019) LEVI, Jose Eduardo; MARTINS, Toni Ricardo; LONGATTO-FILHO, Adhemar; COHEN, Diane Dede; CURY, Use; FUZA, Luiz Mario; VILLA, Luisa L.; ELUF-NETO, JoseEvery year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of Sao Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to I IPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class >= ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7,2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2(+)) cases were diagnosed, 79 were Hr-HPV DNA(+) and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3(+) cases were Hr-HPV DNA(+). HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3(+). Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.
- HPV genotype distribution in Brazilian women with and without cervical lesions: correlation to cytological data(2016) MARTINS, Toni Ricardo; OLIVEIRA, Cristina Mendes de; ROSA, Luciana Reis; CENTRONE, Cristiane de Campos; RODRIGUES, Celia Luiza Regina; VILLA, Luisa Lina; LEVI, Jose EduardoBackground: Human Papillomavirus (HPV) genotype distribution varies according to the method of assessment and population groups. This study analyzed type-specific HPV infections among women ranging from 14-95 years old, displaying normal and abnormal cytology, from Sao Paulo and Barretos cities, Brazil. Methods: Women found positive for High Risk-HPVs DNA by either the Hybrid Capture 2 (HC2) or Cobas HPV Test (n = 431) plus a random sample of 223 negative by both assays and 11 samples with indeterminate results, totalizing 665 samples, were submitted to HPV detection by the PapilloCheck test. Cytological distribution included 499 women with a cytological result of Negative for Intraepithelial Lesion or Malignancy and 166 with some abnormality as follows: 54 Atypical Squamous Cells of Undetermined Significance; 66 Low-Grade Squamous Intraepithelial Lesion; 43 High-Grade Squamous Intraepithelial Lesion and 3 (0.5 %) Invasive Cervical Cancer. Results: From the 323 samples (48.6 %) that had detectable HPV-DNA by the PapilloCheck assay, 31 were HPV negative by the cobas HPV and HC2 assays. Out of these 31 samples, 14 were associated with HR-HPVs types while the remaining 17 harbored exclusively low-risk HPVs. In contrast, 49 samples positive by cobas HPV and HC 2 methods tested negative by the PapilloCheck assay (19.8 %). Overall, the most frequent HR-HPV type was HPV 16 (23.2 %), followed by 56 (21.0 %), 52 (8.7 %) and 31 (7.7 %) and the most frequent LR-HPV type was HPV 42 (12.1 %) followed by 6 (6.2 %). Among the HR-HPV types, HPV 56 and 16 were the most frequent types in NILM, found in 19. 1 and 17.7 % of the patients respectively while in HSIL and ICC cases, HPV 16 was the predominant type, detected in 37.2 and 66.7 % of these samples. Conclusions: In the population studied, HPV 16 and 56 were the most frequently detected HR-HPV types. HPV 56 was found mainly in LSIL and NILM suggesting a low oncogenic potential. HPV 16 continues to be the most prevalent type in high-grade lesions whereas HPV 18 was found in a low frequency both in NILM and abnormal smears. Surveillance of HPV infections by molecular methods is an important tool for the development and improvement of prevention strategies.
- Influence of Prior Knowledge of Human Papillomavirus Status on the Performance of Cytology Screening(2018) MARTINS, Toni Ricardo; LONGATTO-FILHO, Adhemar; COHEN, Diane; VISCONDI, Juliana Yukari Kodaira; FUZA, Luiz Mario; CURY, Lise; VILLA, Luisa Lina; LEVI, Jose Eduardo; ELUF-NETO, JoseObjectives: This study aimed to evaluate the influence of prior knowledge of human papillomavirus (HPV) status in cervical cytopathology readings. Methods: Participants comprised 2,376 women who underwent parallel cytology and HPV-DNA testing. Smears were read twice by the same team, first with previous knowledge of HPV-DNA status. Results: Overall, 239 (10.2%) smears had their cytology classification altered by the HPV-informed review. Cytology readings with prior knowledge of the HPV status revealed 10.5% of abnormal smears (atypical squamous cells of undetermined significance or higher), while without prior knowledge, this rate dropped to 7.6%. When HPV status was informed, a significant increase in all categories of altered smears was observed. Cytology with prior knowledge of HPV status detected more cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) compared with blinded: 86.7% vs 60.0%. Conclusions: Our data indicate that cytology interpreted with prior knowledge of the HPV status provides higher sensitivity for CIN 2+ lesions while marginally reducing the overall specificity compared with HPV status blinded cytology.
- IMPACT OF THE COVID-19 PANDEMIC ON CERVICAL CANCER SCREENING IN SAOPAULO STATE, BRAZIL(2023) MARTINS, Toni Ricardo; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia; GODOY, Amanda Scancella de; CURY, Lise; BALANCIN, Marcelo Luiz; AB'SABER, Alexandre Muxfeldt; PERES, Stela Verzinhasse; MESSIAS, Sandra; MENDONZA, Tania Regina Tozetto; LONGATTO-FILHO, AdhemarINTRODUCTION: The early identification of precursor lesions followed by appropriate treatment prevents development of cervical cancer and its consequences OBJECTIVE: The present study evaluated the influence of the Covid-19 pandemic on cervical cancer screening by comparing the quantity of tests to detect cervical cellular changes performed in Sao Paulo state in 2019, prior to the detection of SARS-CoV-2 in Brazil, to the first (2020) and second (2021) years following its appearance. MATERIALS AND METHODS: Data from Fundacao Oncocentro de Sao Paulo (FOSP), the agency that analyses approximately 220,000 Pap tests annually, was reviewed. RESULTS: A median of 1835 Papanicolaou (Pap) tests were performed in 55 municipalities in 2019. This was reduced to 815 tests in 2020, a 56% decrease (p = 0.0026). In 2021, the median number was 1745, a 53% increase over 2020 levels (p = 0.0233). The 26 municipalities with >1000 tests in 2020 had a median reduction from 4433 in 2019 to 2580 in 2020 (p = 0. 0046). The 29 municipalities with <1000 tests had a median reduction from 951 in 2019 to 554 in 2020 (p < 0.0001). There was a 44% reduction in the number of follow-up cytological evaluations from 2019 to 2020, followed by a 30% increase the following year. However, the percentage of women with a normal finding or with any abnormality remained unchanged. The findings from a histological evaluation of women in Sao Paulo city indicated that the percent of cases positive for CIN-1 (p<0.0410) and CIN-3 (p<0.0012) increased in 2020 and 2021 as compared to 2019 levels. CONCLUSION: A reduction in testing for cervical cancer in the first year of the Covid-19 pandemic, accompanied by an elevated incidence of precancerous lesions in each of the first two years following its initiation, may portend a subsequent increased occurrence of cervical cancer in Brazil.
- Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection(2023) RUSSO, Momtchilo; MENDES-CORREA, Maria Cassia; LINS, Bruna B.; KERSTEN, Victor; PERNAMBUCO, Paulo C. A.; MARTINS, Toni Ricardo; TOZETTO-MENDOZA, Tania Regina; BOAS, Lucy Santos Vilas; GOMES, Brisa Moreira; DATI, Livia Mendonca Munhoz; DUARTE-NETO, Amaro Nunes; REIGADO, Gustavo Roncoli; FREDERICO, Ana Beatriz T.; CUNHA, Danielle R. de A.; PAULA, Anderson Vicente de; SILVA, Jose Igor G. da; VASCONCELOS, Carlos F. Moreira; CHAMBERGO, Felipe S.; NUNES, Viviane Abreu; BOM, Ana Paula Dinis Ano; CASTILHO, Leda R.; MARTINS, Rodrigo A. P.; HIRATA, Mario Hiroyuki; MIROTTI, Luciana; TRIPP, Ralph A.Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
- Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival(2017) GENTA, Maria Luiza Nogueira Dias; MARTINS, Toni Ricardo; LOPE, Rossana V. Mendoza; SADALLA, Jose Carlos; CARVALHO, Joao Paulo Mancusi de; BARACAT, Edmund Chada; LEVI, Jose Eduardo; CARVALHO, Jesus PaulaBackground Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods Women diagnosed with ICC at the Instituto do Ca A ncer do Estado de Sao Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity (TM) system (BD Viper (TM) LT automated system). Results 292 patients aged 50 +/- 14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35-21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD (TM) assay provides a simpler alternative for routine clinical use.
- Moving towards a strategy to accelerate cervical cancer elimination in a high-burden city-Lessons learned from the Amazon city of Manaus, Brazil(2021) TORRES, Katia Luz; RONDON, Heidy Halanna de Melo Farah; MARTINS, Toni Ricardo; MARTINS, Sandro; RIBEIRO, Ana; RAIOL, Taina; MARQUES, Carla Pintas; CORREA, Flavia; MIGOWSKI, Arn; MINUZZI-SOUZA, Thais Tamara Castro e; SCHIFFMAN, Mark; RODRIGUEZ, Ana Cecilia; GAGE, Julia C.The World Health Organization Call to Eliminate Cervical Cancer resonates in cities like Manaus, Brazil, where the burden is among the world's highest. Manaus has offered free cytology-based screening since 1990 and HPV immunization since 2013, but the public system is constrained by many challenges and performance is not well-defined. We obtained cervical cancer prevention activities within Manaus public health records for 2019 to evaluate immunization and screening coverage, screening by region and neighborhood, and the annual Pink October screening campaign. We estimated that among girls and boys age 14-18, 85.9% and 64.9% had 1+ doses of HPV vaccine, higher than rates for age 9-13 (73.4% and 43.3%, respectively). Of the 90,209 cytology tests performed, 24.9% were outside the target age and the remaining 72,230 corresponded to 40.1% of the target population (one-third of women age 25-64). The East zone had highest screening coverage (49.1%), highest high-grade cytology rate (2.5%) and lowest estimated cancers (38.1/100,000) compared with the South zone (32.9%, 1.8% and 48.5/100,000, respectively). Largest neighborhoods had fewer per capita screening locations, resulting in lower coverage. During October, some clinics successfully achieved higher screening volumes and high-grade cytology rates (up to 15.4%). Although we found evidence of some follow-up within 10 months post-screening for 51/70 women (72.9%) with high-grade or worse cytology, only 18 had complete work-up confirmed. Manaus has successfully initiated HPV vaccination, forecasting substantial cervical cancer reductions by 2050. With concerted efforts during campaigns, some clinics improved screening coverage and reached high-risk women. Screening campaigns in community locations in high-risk neighborhoods using self-collected HPV testing can achieve widespread coverage. Simplifying triage and treatment with fewer visits closer to communities would greatly improve follow-up and program effectiveness. Achieving WHO Cervical Cancer Elimination goals in high-burden cities will require major reforms for screening and simpler follow-up and treatment.