ADHEMAR LONGATTO FILHO

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LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina

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  • article 1 Citação(ões) na Scopus
    Longitudinal outcomes of high-risk human papillomavirus (HPV) infections as competing-risks events following cervical HPV test at baseline visit in the *NIS-LAMS** cohort
    (2012) SYRJANEN, K.; SHABALOVA, I.; SARIAN, L.; NAUD, P.; LONGATTO-FILHO, A.; DERCHAIN, S.; KOZACHENKO, V.; ZAKHARCHENKO, S.; ROTELI-MARTINS, C.; NEROVJNA, R.; KLJUKINA, L.; TATTI, S.; BRANOVSKAJA, M.; BRANCA, M.; GRUNJBERGA, V.; ERZEN, M.; JUSCHENKO, A.; HAMMES, L. Serpa; PODISTOV, J.; COSTA, S.; SYRJANEN, S.
    Background: The complex natural history of human papillomavirus (HPV) infections following a single HPV test can be modeled as competing-risks events (i.e., no-, transient- or persistent infection) in a longitudinal setting. The covariates associated with these compet ng events have not been previously assessed using competing-risks regression models. Objectives: To gain further insights in the outcomes of cervical HPV infections, we used univariate- and multivariate competing-risks regression models to assess the covariaies associated with these competing events. Study Design and Methods: Covariates associated with three competing outcomes (no-, transient- or persistent HR-HPV infection) were analysed in a sub-cohort of 1,865 women prospectively followed-up in the NIS (n = 3,187) and LAMS Study (n = 12,114). Results: In multivariate competing-risks models (with two other outcomes as competing events), permanently HR-HPV negative outcome was significantly predicted only by the clearance of ASCUS+Pap during FU, while three independent covariates predicted transient HR-HPV infections: i) number of recent (< 12 months) sexual partners (risk increased), ii) previous Pap screening history (protective), and history of previous CIN (increased risk). The two most powerful predictors of persistent HR-HPV infections were persistent ASCUS+Pap (risk increased), and previous Pap screening history (protective). In pair-wise comparisons, number of recent sexual partners and previous CIN history increase the probability of transient HR-HPV infection against the HR-HPV negative competing event, while previous Pap screening history is protective. Persistent ASCUS+Pap during FU and no previous Pap screening history are significantly associated with the persistent HR-HPV outcome (compared both with i) always negative, and ii) transient events), whereas multiparity is protective. Conclusions: Different covariates are associated with the three main outcomes of cervical HPV infections. The most significant covariates of each competing events are probably distinct enough to enable constructing of a risk-profile for each main outcome.
  • article 8 Citação(ões) na Scopus
    Characterization of topoisomerase II alpha and minichromosome maintenance protein 2 expression in anal carcinoma
    (2017) SCAPULATEMPO-NETO, Cristovam; VEO, Carlos; FREGNANI, Jose Humberto T. G.; LORENZI, Adriana; MAFRA, Allini; MELANI, Armando G. F.; LOAIZA, Edgar Antonio Aleman; ROSA, Luciana Albina Reis; OLIVEIRA, Cristina Mendes De; LEVI, Jose Eduardo; LONGATTO-FILHO, Adhemar
    The present study aimed to ascertain the significance of topoisomerase II alpha (TOP2A) and minichromosome maintenance protein (MCM) 2 expression in anal carcinoma. A total of 75 anal lesions were retrieved from the files of the Department of Pathology of Barretos Cancer Hospital (Barretos, Brazil) in order to verify the human papillomavirus (HPV) statuses of these lesions and characterize the immunohistochemical expression levels of TOP2A and MCM2 in anal carcinoma, as these are important markers for cervical HPV-induced lesions; their expression was also compared with respect to p16 and Ki-67. The vast majority of the cases tested positive for HPV16 (84%); 1 case tested positive for both HPV16 and HPV18. Positive HPV16 status was more frequent in early stages than in advanced stages (P=0.008). Positive immunohistochemical reactivity for MCM2 and TOP2A protein was observed in 71.6 and 100% of cases, respectively. Positive reactivity for p16 was significantly associated (P=0.001) with histological grade, and was more commonly expressed in squamous cell carcinoma than adenocarcinomas. HPV16 was strongly associated with positive p16 protein expression (76.6%). However, the high expression of Ki-67 combined with the high expression of p16 was predominantly observed in Stage III-IV cases. MCM2, TOP2A, p16 and Ki-67 exhibited intense positive staining in the anal lesions, indicating that these markers were significantly and constantly expressed in anal carcinoma.
  • article 11 Citação(ões) na Scopus
    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, Jose
    Every 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.
  • article 0 Citação(ões) na Scopus
    Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review
    (2023) BOVO, Adriane Cristina; PEDRAO, Priscila Grecca; GUIMARAES, Yasmin Medeiros; GODOY, Luani Rezende; RESENDE, Julio Cesar Possati; LONGATTO-FILHO, Adhemar; REIS, Ricardo dos
    Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of similar to 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.
  • article 2 Citação(ões) na Scopus
    Polymorphism of Interleukin-6 Is Not Associated with the Presence or Absence of High HPV E6/E7
    (2014) PORTO, Claudia Regina Cinti; KLEINE, Joao Paulo Ferreira De Oliveira; LONGATTO FILHO, Adhemar; SILVA, Ismael Dale Cotrim Guerreiro Da
    The present study evaluated the frequency of the polymorphism of Interleukin-6 (IL6) in women positive for E6/E7 Human Papillomavirus (HPV) (n=152) and women negative for HPV (n=238), 390 women in total. Material for analysis was obtained at the Federal University of Sao Paulo. Interleukin-6 polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and analyzed in 3% agarose gel. Results: No significant associations between the frequency of the polymorphism of IL6 in patients expressing E6 and E7 with HPV-positive and -negative reactions were found. There was no statistically significant difference between the case and control group for genotype distribution (p=0.280). Conclusion: Genotypic analysis showed a striking similarity of IL6 polymorphisms in both cases and controls. The allelic distribution in cases and controls for G and C of IL6 were very similar (p=0.186), which could point to similar IL6 functionality for both groups.
  • article 15 Citação(ões) na Scopus
    Frequency of Chlamydia trachomatis infection in cervical intraepithelial lesions and the status of cytological p16/Ki-67 dual-staining
    (2017) ROBIAL, R.; LONGATTO-FILHO, A.; ROTELI-MARTINS, C. M.; SILVEIRA, M. F.; STAUFFERT, D.; RIBEIRO, G. G.; LINHARES, I. M.; TACLA, M.; ZONTA, M. A.; BARACAT, E. C.
    Background: Chlamydia trachomatis (Ct) is not a disease subject to mandatory reporting in Brazil, and the prevalence rate of this genital infection varies according to the region in which studies are conducted, as well as by the detection technique employed. Ct has been associated with persistence of Human papillomavirus (HPV) infection and the facilitation of cervical carcinoma development. We evaluated the Chlamydia trachomatis infection and its association with cytology, p16/Ki-67 dual-stained cytology and cervical intraepithelial lesions status in a screening cohort in Brazil. Methods: This was a cross-sectional study of 1481 cervical samples from asymptomatic women aged 18 to 64. Samples were collected for liquid-based cytology and Ct detection by polymerase chain reaction. p16/Ki-67 double staining was performed on samples with abnormal cytology. Statistical analysis was by chi-square and likelihood-ratio tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were determined. Results: The frequency of Ct was 15.6% and its presence was not associated with detection of p16/Ki-67 [OR = 1. 35 (0.5-3.4)]. There was also no association between abnormal cervical cytology and Ct-positivity [OR = 1.21 (0.46-3.2)]. Associations were observed between p16/Ki-67 and high-grade lesions detected by cytology and in biopsies [OR = 3.55 (1.50-8.42) and OR = 19.00 (0.6-7.2), respectively]. Conclusions: The asymptomatic women in our study had a high frequency of Ct infection but this was not associated with p16/Ki-67 detection in samples with abnormal cytology. The expression of p16/Ki-67 was highest in women with high-grade CIN (p = 0.003).
  • article 11 Citação(ões) na Scopus
    Predictor Variables and Screening Protocol for Depressive and Anxiety Disorders in Cancer Outpatients
    (2016) LIMA, Manuela Polidoro; LONGATTO-FILHO, Adhemar; OSORIO, Flavia L.
    Background Cancer patients are at increased risk of persistent depressive and anxiety symptoms and disorders compared to the general population. However, these issues are not always identified, which may worsen the prognosis and increase morbidity and mortality. Therefore, the objectives of this study are to identify predictor variables (demographic and clinical) for the development of mood and anxiety disorders in cancer outpatients and to propose a probabilistic screening protocol considering these variables and certain standardized screening instruments. Methods A total of 1,385 adults, of both genders, receiving outpatient cancer care were evaluated using a questionnaire and screening instruments. Thereafter, 400 of these subjects responded to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-IV) by telephone to confirm or rule out the presence of a Current Major Depressive Episode (CMDE) or Anxiety Disorder (AD). Results Of the patients surveyed, 64% met the criteria for CMDE and 41% for AD. Female gender was found to be a risk factor for both disorders, and the presence of previous psychiatric history and marital status (divorced and widowed) were risk factors for anxiety disorders. When scoring above the recommended cutoff score, the screening instruments also indicated a risk of the studied disorders. Based on these findings, a screening protocol and nomograms were created for the quantification, combination and probabilistic estimate of risk, with accuracy indicators >0.68. Conclusion The prevalence rates for the disorders under study are extremely high in cancer patients. The use of the proposed protocol and nomogram can facilitate rapid and wide screening, thus refining triage and supporting the establishment of criteria for referral to mental health professionals, so that patients can be properly diagnosed and treated.
  • article 31 Citação(ões) na Scopus
    MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis
    (2015) DISCACCIATI, Michelle G.; GIMENES, Fabrcia; PENNACCHI, Paula C.; FAIAO-FLORES, Fernanda; ZEFERINO, Luiz C.; DERCHAIN, Sophie M.; TEIXEIRA, Julio C.; COSTA, Maria C.; ZONTA, Marco; TERMINI, Lara; BOCCARDO, Enrique; LONGATTO-FILHO, Adhemar; CONSOLARO, Marcia E. L.; VILLA, Luisa L.; MARIA-ENGLER, Silvya S.
    Background: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. Methods: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. Results: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). Conclusions: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. Impact: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis. (C) 2015 AACR.
  • article 11 Citação(ões) na Scopus
    Organized Cervical Cancer Screening Program in Barretos, Brazil: Experience in 18 Municipalities of Sao Paulo State
    (2018) POSSATI-RESENDE, Julio Cesar; VAZQUEZ, Fabiana de Lima; BIOT, Sinval Tadeu; MAUAD, Edmundo Carvalho; TALARICO, Thais; FREGNANI, Jose Humberto Tavares Guerreiro; LONGATTO-FILHO, Adhemar
    Objectives: The aim of this report is to demonstrate the Barretos Cancer Hospital initiative of organizational, laboratorial, and human resources training in the implementation of an organized cervical screening program in low-resource settings. Methods: We developed a computational program to report all epidemiological, clinical, and laboratorial findings, and to trace all necessary information to recruit women for regular screening or for referral for complementary exams after liquid-based Pap test analyses. Results: All Pap tests were collected in liquid medium and in 2014 more than 160,000 tests were analyzed and 2,900 colposcopy examinations were performed. From 2012 to 2015, the percentage of exams collected increased from 54.6% in 2012 to 62.4% in 2013, 68.4% in 2014, and 71% in 2015. Per 1,000 Pap tests, 0.4 cases of invasive cancer were diagnosed; for in situ carcinoma, 1.9 cases were identified. More importantly, between 2011 and 2015, 89.4% of all carcinomas were detected at clinical stage 0 or I (in situ carcinoma), and only 5% at stages III and IV. Conclusions: Since the organized system was implemented, 98% of women have attended their recall for colposcopy. So far, we have not reached the target of 70% of women for this proposal, as recommended by the international standards. (C) 2017 S. Karger AG, Basel
  • article 7 Citação(ões) na Scopus
    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, Jose
    Objectives: 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.