ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
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article 12 Citação(ões) na Scopus The Impact of Breast Cancer Screening Among Younger Women in the Barretos Region, Brazil(2013) MATTOS, Jaco Saraiva De Castro; MAUAD, Edmundo Carvalho; SYRJANEN, Kari; LONGATTO-FILHO, Adhemar; HAIKEL, Raphael Luiz; VIEIRA, Rene Aloisio Da Costa; SILVA, Thiago Buosi; BARROS, Nestor DeAim: To verify the impact of breast cancer screening in women aged 40-49 years in one region of Brazil. Patients and Methods: This is a cross-sectional study, targeted to asymptomatic women aged 40-69 years who had breast cancer screening mammography performed between January 2003 and December 2007. Logistic regression was used to estimate the risk of breast cancer by age groups (40-49, 5059, 60-69 years). Results: Of the 27,133 screened women, 51.9% (14,082) were aged between 40-49 years. The odds ratio (OR) of breast cancer among the 45-49 year age cohort was not significantly different from that of 60 to 69-year-old women (OR=0.64; 95% Confidence Interval 0.39 to 1.03). Conclusion: The risk of breast cancer among women aged 45 to 49 years is equivalent to that of women aged 60 to 69 years, indicating that breast cancer screening in this region of Brazil should start at the age of 45 years or immediately thereafter.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 5 Citação(ões) na Scopus Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models(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: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident i) CIN1 are different from those of incident ii) CIN2 and iii) CIN3 needs further assessment. Objectives: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. Study Design and Methods: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3,187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1,105), who represent a sub-cohort of all 1,865 women prospectively followed-up in these two studies. Results: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident GIN I, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. Conclusions: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of GIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common end-point, e.g., in HPV vaccine trials.- The relationship between esophageal cancer, chagasic megaesophagus and HPV: myths, tales or reality?(2018) MUNARI, Fernanda Franco; CARLONI, Adriana Cruvinel; MARIANO, Vania Sammartino; SYRJANEN, Kari; REIS, Rui Manuel; LONGATTO-FILHO, AdhemarA supposed role for persistent high-risk human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) etiology has been suggested by a number of studies. Concomitantly, megaesophagus induced by the Trypanosoma cruzi cell-cycle activity also shows a potential association with ESCC. This review discusses esophageal cancer and the potential association between chagasic megaesophagus and HPV as risk factors for ESCC development.
- High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer(2017) SILVA, Estela Maria; MARIANO, Vania Sammartino; PASTREZ, Paula Roberta Aguiar; PINTO, Miguel Cordoba; CASTRO, Antonio Gil; SYRJANEN, Kari Juhani; LONGATTO-FILHO, AdhemarCharacteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-gamma) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient's clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III-IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.
- Detection of human papillomavirus in laryngeal squamous cell carcinoma: Systematic review and meta-analysis(2016) GAMA, Ricardo Ribeiro; CARVALHO, Andre Lopes; LONGATTO FILHO, Adhemar; SCORSATO, Anderson Paulo; LOPEZ, Rossana V. Mendoza; RAUTAVA, Jaana; SYRJAENEN, Stina; SYRJAENEN, KariBackgroundRecent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies. ObjectiveTo perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC. MethodsLiterature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [CI]), with homogeneity testing using Cochran's Q and I-2 statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size. Potential publication bias was estimated using funnel plot symmetry. ResultsOne hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non-polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both. ConclusionsVariability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression. Level of EvidenceNA Laryngoscope, 126:885-893, 2016
- Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN(2011) LONGATTO-FILHO, Adhemar; HAMMES, Luciano Serpa; SARIAN, Luis Otavio; ROTELI-MARTINS, Cecilia; DERCHAIN, Sophie F. M.; ERZEN, Mojca; BRANCA, Margherita; TATTI, Silvio; NAUD, Paulo; MATOS, Jean Carlos de; GONTIJO, Renata; MAEDA, Marina Y. S.; LIMA, Temistocles; COSTA, Silvano; SYRJANEN, Stina; SYRJANEN, KariAims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort.
- Retrospective analysis of breast cancer prognosis among young and older women in a Brazilian cohort of 738 patients, 1985-2002(2016) VAZQUEZ, Fabiana De Lima; SILVA, Thiago Buosi; VIEIRA, Rene Alonisio Da Costa; COSTA, Allini Mafra Da; SCAPULATEMPO, Cristovam; FREGNANI, Jose Humberto Tavares Guerreiro; MAUAD, Edmundo Carvalho; LONGATTO, Adhemar; SYRJANEN, Kari JuhaniInvasive breast cancer (BC) is infrequent among women aged.5.40 years, however, the disease outlook in these younger patients is generally worse than among older women. The present study aimed to compare socio-demographic, clinical and pathological characteristics, and their association with long-term survival, between two random cohorts of young (<= 40 years) and older (50-69 years) Brazilian patients with BC. The cohort comprised of 738 randomly selected women who were diagnosed with BC at Barretos Cancer Hospital, Pio XII Foundation (Barretos, Brazil) between January 1985 and December 2002; the patients included young women (n=376) and older women (n=362). The current analysis suggested that BC in young women is associated with numerous pathological features of aggressiveness. Second cancer and bilateral BC were independent predictors of a poor outcome in the younger group. Furthermore, C-erB-2 was positively correlated with poor outcome in the older group, whereas estrogen receptor status and TNM stage were associated with disease prognosis in both groups. The overall survival rates of the two age groups were similar except when analyzed according the treatment period (1997-2002). Although patients aged <= 40 years harbored tumors with more aggressive clinicopathological characteristics, these characteristics were not independent predictors of overall survival. The present study indicates that medical advances associated with prevention of breast cancer may improve screening programs, which may therefore increase early diagnosis and subsequently lower mortality rates.
- Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective(2015) LORENZI, Adriana T.; SYRJANEN, Kari J.; LONGATTO-FILHO, AdhemarThis review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.
- Physical state and copy numbers of HPV16 in oral asymptomatic infections that persisted or cleared during the 6-year follow-up(2017) LORENZI, Adriana; RAUTAVA, Jaana; KERO, Katja; SYRJANEN, Kari; LONGATTO-FILHO, Adhemar; GRENMAN, Seija; SYRJANEN, StinaPersistent human papillomavirus (HPV) infection is a key event in HPV-induced carcinogenesis. As part of the prospective Finnish Family HPV Study, we analysed the physical state and viral copy numbers of HPV16 in asymptomatic oral infections that either persisted or cleared during the 6-year follow-up. The persister group comprised 14 women and 7 men with 51 and 21 HPV16-positive brush samples. The clearance group included 41 women and 13 men, with 64 and 24 samples, respectively. Physical state and viral DNA load were assessed by using quantitative PCR for HPV16 E2 and E6 genes. E2/ E6 ratio was calculated and HPV16 was classified as episomal, mixed or integrated with values of 0.93-1.08, <0.93 and 0, respectively. In both genders, the physical state of HPV16 was significantly different between the cases and controls (P<0.001). HPV16 was episomal in all men and 66% (27/41) of women who cleared their infection. HPV16 was mixed and/or integrated in71% and 57 % of the women and men persisters, respectively. The mean HPV16 copy number per 50 ng genomic DNA was nearly 5.5-fold higher in the women than in the men clearance group (P= 0.011). Only in men, HPV16 copy numbers were higher in persisters than in the clearance group (P= 0.039). To conclude, in both genders, persistent oral HPV16 infections were associated with the mixed or integrated form of HPV16, while in the clearance groups, episomal HPV16 predominated. This indicates that HPV16 integration is a common event even in asymptomatic oral infections, which might predispose the infected subjects to progressive disease.