K Syrjänen

Hospital de Câncer de Barretos, San Paulo, São Paulo, Brazil

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Publications (310)920.46 Total impact

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    ABSTRACT: The prospective Finnish Family HPV Study evaluated the dynamics of human papillomavirus (HPV) infection within families. Here, we focused on HPV serology in men. Seroprevalence at baseline, seroconversion and decay of low-risk (LR)-HPV6 and 11, and high risk (HR)-HPV16, 18 and 45 L1 antibodies in 122 men at 12, 24 and 36 months were determined using Luminex-based multiplex HPV serology, and correlated with demographic data. At baseline, seropositivity to HPV6, 11, 16, 18 and 45 was observed in 41.0, 11.5, 23.0, 13.9 and 5.7 % of the men, respectively. In univariate analysis, LR-HPV seropositivity was related to smoking status, history of genital warts and being seropositive to HR-HPV. Oral HR-HPV DNA and baseline LR-HPV seropositivity predicted HR-HPV seropositivity. Seroconversion to HPV6, 11, 16, 18 and 45 antigens during follow-up was found in 24.6, 11.5, 5.7, 5.7 and 0.8 %, respectively. Seroconversion to LR-HPV was negatively related to a higher number of children and oral sex, and positively associated with seroconversion to HR-HPV. In multivariate analysis, the same predictors remained significant except for the number of children. In univariate generalised estimating equations (GEE) for HR-HPV, being seroconverted to LR-HPV was the only predictor, but lost its significance in multivariate analyses. Decay of all HPV L1 antibodies was rare and observed in 0-2 %. The HPV antibody profile in men was dominated by response to HPV6, also showing the highest cumulative seroconversion. Oral HPV infection might affect HPV serology: (1) HPV DNA in oral mucosa is associated with baseline HR-HPV seropositivity and (2) practising oral sex significantly reduces longitudinal seroconversion to HPV6 and/or 11.
    08/2014;
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    ABSTRACT: Human papillomavirus (HPV) infections are associated with sexual behavior. Changes in the sexual habits of couples and their impact on male genital and oral HPV infections were determined during 7 years of follow-up (FU). At baseline and 7 years FU, urethral, semen/penile, and oral samples were collected from 46 men and cervical and oral samples of their spouses for HPV DNA detection. Demographic data and risk factors of spouses were recorded by questionnaire at both time points and analyzed for concordance. HPV genotyping was done with the Multimetrix® kit. At baseline, 29.5 % of the male genital and 11 % of their oral samples tested positive. Incident genital HPV infection was found in 23 % and oral infection in 10.9 % of men. Genotype-specific persistence was detected in one man (HPV53) in genital samples. Moderate to almost perfect concordance of changes in sexual habits during FU among spouses were found. Changing partners [p = 0.028; odds ratio (OR) = 15; 95 % confidence interval (CI) 1.355-166.054] and marital status (p = 0.001; 95 % CI 0.000-0.002) increased the risk of incident genital HPV infections. The overall outcome of genital HPV disease in men was linked to the frequency of sexual intercourse (p = 0.023; 95 % CI 0.019-0.026) and changes in marital status (p = 0.022; 95 % CI 0.019-0.026), while oral HPV infections were associated with the number of sexual partners (p = 0.047; 95 % CI 0.041-0.052). Taken together, asymptomatic genital HPV infections among the men were common. The risk of incident genital HPV infections increased among men reporting a change of sexual partner during FU, implicating that a stable marital relationship protects against oral and genital HPV infection.
    European Journal of Clinical Microbiology 02/2014; · 3.02 Impact Factor
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    ABSTRACT: Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in the progression of HPV lesions, and more data are urgently needed on asymptomatic oral HPV infections in men. Asymptomatic fathers-to-be (n = 131, mean age 28.9 years) were enrolled in the cohort, sampled by serial oral scrapings at baseline and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up visits to accomplish persistent and cleared HPV infections. HPV genotyping was performed using nested PCR and Multimetrix® assay. Covariates of persistent and cleared oral HPV infections were analysed using generalised estimating equation (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific HPV persistence was detected in 18/129 men the mean persistence time ranging from 6.0 to 30.7 months. History of genital warts decreased (p = 0.0001; OR = 0.41, 95 % CI 0.33-0.51) and smoking increased (p = 0.033, OR = 1.92, 95 % CI 1.05-3.50) the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men, 71.6 % cleared their infection actuarial and crude clearance times, varying between 1.4 and 79.6 months. No independent predictors were identified for species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had oral mucosal changes, correlating only with smoking (p = 0.046). To conclude, most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. No predictors of HR-HPV clearance were disclosed.
    European Journal of Clinical Microbiology 09/2013; · 3.02 Impact Factor
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    ABSTRACT: Background. Lung cancer and mesothelioma are malignant tumors with generally dismal prognosis and therefore palliative pain treatment constitutes a challenge for the clinician. Objectives. The aim of this study was to compare the outcomes of pain treatment with opioids among mesothelioma and lung cancer patients treated for palliation and assess factors which confound to optimal treatment. Patients and methods. A sub-cohort of 373 lung cancer and 22 mesothelioma patients was identified in multi-center European Pharmacogenetic Opioid Study (EPOS) cohort. A nested case-control (1:4) setting was designed to estimate the pain and other covariates distinguishing 22 mesothelioma- (= cases) and 88 lung cancer patients (controls), analyzed using univariate- and multivariate conditional (fixed-effects) logistic regression models. Results. The mean total daily dose of opioids varied from 30.0 to 960.0 mg (mean 275, median 160 mg, SD 293) in mesothelioma, and from 10 to 5072 mg (mean 414, median 175, SD 788) in lung cancer patients (p = 0.420). In both groups, pain was mostly experienced as moderate and severe and it was frequently accompanied by depression, poor sleep, anxiety and fatigue. Four mesothelioma patients (18%) and seven lung cancer patients (10%) experienced complete pain relief with opioids by self-assessment. Assessments of pain severity by the patients and their physicians deviated significantly in mesothelioma (p = 0.039 McNemar test), as well as in lung cancer (p = 0.0001). In conditional logistic regression, no significant differences were found in distribution of pain covariates between lung cancer and mesothelioma patients. Conclusion. Pain perception by the patients was associated frequently with other symptoms and complete pain control with opioids was achieved only with minority of patients both with mesothelioma and advanced lung cancer. Adequate pain control requires continuous monitoring and tailoring the dose to patient's individual needs and tolerance, recognition of accompanying symptoms such as depression and poor sleep, and their management.
    Acta oncologica (Stockholm, Sweden) 10/2012; · 2.27 Impact Factor
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    ABSTRACT: Since first suggested in 1979, evidence on the involvement of human papillomavirus (HPV) in bronchial carcinogenesis has been accumulated through several lines of research. The causal role of HPV in lung cancer still remains controversial, however, and more data are needed particularly on genotype distribution and cofactors of HPV regarding this disease. The present series consists of 77 patients diagnosed and treated for lung cancer at the Department of Respiratory Medicine, Turku University Hospital, (Finland) during 2008-2010. All available histological samples (n=77) were subjected to HPV genotyping with the Luminex-based Multimetrix kit, detecting 24 low-risk (LR) and high-risk (HR) HPV types. Pertinent clinical data were collected and subjected to univariate and multivariate regression analysis to disclose the covariates associated with HPV detection in lung cancer. Out of 77 histological samples analyzed, four (5.2%) (three squamous cell and one adenocarcinoma) were found to be HPV-positive, out of which three were HPV16 infections and one a double-infection with HPV6 and HPV16. All four patients were males, and all but one reported no asbestos exposure. Three of them had refrained from smoking for a period >22 years. Disease-specific survival was twice as long for individuals with HPV+ than those with HPV- tumors (25.5 vs. 12.8 months), but confounding by treatment cannot be excluded. In univariate analysis, four covariates were significantly associated with HPV detection: i) older age (p=0.003) ii) older age at smoking initiation (p=0.027), iii) fewer years of active smoking (p=0.036), and iv) fewer total pack years (p=0.002). In a multivariate regression model adjusted to all significant covariates, only absolute age was significantly associated with testing as HPV-positive (odds ratio=1.16, 95% confidence interval 1.04-1.39, p=0.008). Given the fact that initiation of smoking at an older age, fewer pack years and long smoking abstinence were associated with HPV, it is tempting to speculate that oncogenic HPV can substitute smoking as a risk factor, leading to lung cancer in these patients despite >22 years elapsing since their smoking cessation. In the era of prophylactic HPV vaccination, there is an urgent need to provide more data on the global HPV burden and covariates of the virus associated to lung cancer.
    Anticancer research 02/2012; 32(2):625-31. · 1.71 Impact Factor
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    ABSTRACT: 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 competing events have not been previously assessed using competing-risks regression models. To gain further insights in the outcomes of cervical HPV infections, we used univariate- and multivariate competing-risks regression models to assess the covariates associated with these competing events. 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). In multivariate competing-risks models (with two other outcomes as competing events), permanently HR-HPV negative outcome was significantly predicted only by the clearance ofASCUS+ 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. 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.
    European journal of gynaecological oncology 01/2012; 33(4):341-52. · 0.58 Impact Factor
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    ABSTRACT: 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. 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. HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1105), who represent a sub-cohort of all 1865 women prospectively followed-up in these two studies. 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 CIN1, 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. 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 CIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common endpoint, e.g., in HPV vaccine trials.
    European journal of gynaecological oncology 01/2012; 33(1):5-14. · 0.58 Impact Factor
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    ABSTRACT: To make feasible future clinical trials with new-generation human papillomavirus (HPV) vaccines, novel virological surrogate endpoints of progressive disease have been proposed, including high-risk HPV (HR-HPV) persistence for six months (6M+) or 12 months (12M+). The risk estimates (relative risks [RRs]) of these 'virological endpoints' are influenced by several variables, not yet validated adequately. We compared the impact of three referent groups: (i) HPV-negative, (ii) HPV-transient, (iii) HPV-mixed outcome on the risk estimates for 6M+ or 12M+ HR-HPV persistence as predictors of progressive disease. Generalized estimating equation models were used to estimate the strength of 6M+ and 12M+ HR-HPV persistence with disease progression to squamous intraepithelial lesions (SILs), cervical intraepithelial neoplasia (CIN) grade 1+, CIN2+, CIN/SIL endpoints, comparing three optional reference categories (i)-(iii) in a prospective sub-cohort of 1865 women from the combined New Independent States of the Former Soviet Union (NIS) and Latin American Screening (LAMS) studies cohort (n = 15,301). The RRs of these viral endpoints as predictors of progressive disease are affected by the length of viral persistence (6M+ or 12M+) and the surrogate endpoint (SIL, CIN1, CIN2, CIN/SIL). Most dramatic is the effect of the referent group used in risk estimates, with the HPV-negative referent group giving the highest and most consistent RRs for both 6M+ and 12M+ viral persistence, irrespective of which surrogate is used. In addition to deciding on whether to use 6M+ or 12M+ persistence criteria, and cytological, histological or combined surrogate endpoints, one should adopt the HPV-negative referent group as the gold standard in all future studies using viral persistence as the surrogate endpoint of progressive disease.
    International Journal of STD & AIDS 06/2011; 22(6):315-23. · 1.00 Impact Factor
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    ABSTRACT: In addition to oncogenic 'high-risk' human papillomaviruses (HR-HPV), several co-factors are needed in cervical carcinogenesis, but it is poorly understood whether these HPV co-factors associated with incident cervical intraepithelial neoplasia (CIN) grade 1 are different from those required for progression to CIN2 and CIN3. To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV co-factors increasing the risk of incident CIN1, CIN2 and CIN3. Data from the New Independent States of the Former Soviet Union (NIS) Cohort (n = 3187) and the Latin American Screening (LAMS) Study (n = 12,114) were combined, and co-factors associated with progression to CIN1, CIN2 and CIN3 were analysed using multinomial logistic regression models with all covariates recorded at baseline. HR-HPV-positive women (n = 1105) represented a subcohort of all 1865 women prospectively followed up in both studies. Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2 and CIN3, respectively. Baseline HR-HPV was the single most powerful predictor of incident CIN1, CIN2 and CIN3. When controlled for residual HPV confounding by analysing HR-HPV-positive women only, the risk profiles of incident CIN1, CIN2 and CIN3 were unique. Completely different HPV co-factors were associated with progression to CIN1, CIN2 and CIN3 in univariate and multivariate analyses, irrespective of whether non-progression, CIN1 or CIN2 was used as the reference outcome. HPV co-factors associated with progression to CIN1, CIN2 and CIN3 display unique profiles, implicating genuine biological differences between the three CIN grades, which prompts us to re-visit the concept of combining CIN2 with CIN3 or CIN1.
    International Journal of STD & AIDS 05/2011; 22(5):263-72. · 1.00 Impact Factor
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    ABSTRACT: The aim of this study was to assess glucose transporter-1 (GLUT-1) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Operative samples from 175 rectal cancer patients and 78 preoperative biopsies were analysed for GLUT-1 expression using immunohistochemistry. Forty-six patients received long-course radiotherapy, with/without chemotherapy and tumour regression grade was analysed in these specimens. Negative GLUT-1 expression was seen in 25/78 (32%) of the preoperative biopsies and in 38/78 (49%) of the operative samples. There was no significant correlation of GLUT-1 with common clinicopathological factors. A trend towards longer disease-free survival (DFS) for the long-course radiotherapy group patients was seen with negative/weak GLUT-1 staining intensity (p=0.066) and excellent tumour regression grade (p=0.068) in operative samples. Disease-free survival (p=0.068) and disease-specific survival (p=0.024) of the patients with excellent tumour regression were longer than among the patients with moderate or less regression. A trend towards longer DFS among patients in favour of negative/weak GLUT-1 staining in the operative samples after long-course radiotherapy is demonstrated.
    Anticancer research 01/2011; 31(1):311-5. · 1.71 Impact Factor
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    ABSTRACT: K. Syrjänen, L. Di Bonito, L. Gonçalves, L. Murjal, M. Santamaria, V. Mahovlic, P. Karakitsos, B. Önal and F. C. SchmittCervical cancer screening in Mediterranean countries: implications for the futurePrompted by feedback from the 34th European Congress of Cytology (ECC), the practice of including a special symposium in the programme was continued in the 35th ECC in Lisbon (2009) by arranging a satellite symposium entitled ‘Cervical Cancer Screening in the Mediterranean Countries’. Because of the importance to the future of this discipline, it was felt appropriate to summarize the highlights of this symposium here. Cervical cancer prevention strategies in the countries participating in the symposium (Portugal, Spain, Italy, Croatia, Greece and Turkey) appear to be highly variable. As yet, none of these countries can demonstrate a fully implemented national screening programme, but all are in different phases of designing and/or setting up such a programme, which is important. At present, the time-honoured concept of cervical cancer prevention by Pap smear screening is under review, because prophylactic human papillomavirus (HPV) vaccines demonstrate a potential to prevent the vast majority (albeit not all) of cases of cervical cancer in the foreseeable future. Cervical cancer screening is still needed in this emerging era of HPV vaccination, but clearly the existing screening strategies must be modified to provide a cost-effective combination of vaccination and screening. If the currently evaluated new screening strategies, such as HPV testing followed by cytology triage, become a reality, there is the likelihood that the Pap test will have only a secondary role, subordinate to HPV testing. Supporters of this scenario claim that Pap test performance will deteriorate in vaccinated populations. Reduced positive predictive value (PPV), due to lower disease prevalence, is inevitable, however, and this would also affect HPV tests. Any decline in sensitivity and specificity depends on human performance, and as such is avoidable by taking appropriate preventive measures. As clinical cytologists, we should focus attention on minimizing the risk to the Pap test of falling sensitivity because of unfamiliarity with abnormal cells, and also of reduced specificity if the fear of missing significant disease leads to overcalling of benign abnormalities.
    Cytopathology 11/2010; 21(6):359 - 367. · 1.71 Impact Factor
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    ABSTRACT: To assess the value of hypoxia-inducible factor-1alpha (HIF-1alpha) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Operative samples from 168 rectal cancer patients and 79 respective preoperative biopsies were analyzed for nuclear HIF-1alpha protein expression using immunohistochemistry by three approaches: (a) positive/negative, (b) the percentage of HIF-positive cancer cells and (c) staining intensity. The patients had received either short- (n = 75) or long-course radiotherapy with or without chemotherapy (n = 39) or no treatment preoperatively (n = 54). HIF-1alpha staining was positive in 70% of the diagnostic biopsies but negative in most of the post-radiotherapy specimens (60%). HIF-1alpha expression in the biopsies was downregulated in 56% of samples taken after preoperative treatment, while negative HIF-1alpha expression was upregulated in 25% of samples. Patients who had HIF-negative tumours after long-course radiotherapy had significantly (P = 0.001) better disease-specific survival (DSS) in univariate analysis. In the multivariate (Cox) regression model, HIF-1alpha lost its significance and only being in the preoperative treatment group was an independent predictor of disease-free survival. In a similar Cox model, disease recurrence and the number of metastatic lymph nodes were independent predictors of DSS. HIF-1alpha expression was positive in most of the preoperative biopsies but downregulated in most of the operative samples, implicating that preoperative radiotherapy downregulates HIF-1alpha expression in rectal cancer. Negative HIF expression after preoperative long-course radiotherapy was associated with significantly better DSS.
    Scandinavian Journal of Gastroenterology 12/2009; 45(3):340-8. · 2.33 Impact Factor
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    ABSTRACT: The association of anaemia and other predictors of fatigue was studied in cancer patients on palliative treatment. A cohort of 128 consecutive patients (61 men and 67 women, mean age 63.6 years; range 36-85) was interviewed using the Edmonton Symptom Assessment System (ESAS) questionnaire, with 11 items describing cancer-related symptoms in visual analogue scale (VAS). Routine haematological samples were analysed at the time of interview. Both univariate and multivariate analyses were used to assess the independent predictors of fatigue. Out of the 10 symptoms recorded, fatigue was the single most frequent, reported by 91.3% of the patients, followed by pain (74.8%), sleeplessness (78.0%) and depression (74.2%). Anaemia was a significant determinant of fatigue (p=0.040)(OR=5.09; 95% CI 1.013-25.647). Out of the symptoms recorded, fatigue was significantly associated with depression (p=0.035), loss of appetite (p=0.016), anxiety (p=0.050), and sleeplessness (p=0.016). Total wellbeing was negatively associated with fatigue (OR=0.48, 95% CI 0.011-0.020)(p=0.0001). In multivariate analysis, anaemia was the most powerful independent predictor of fatigue, with OR=38.27 (95% CI 2.62-559.19)(p=0.008), followed by sleeplessness (OR=14.06 95% CI 1.44-137.02 p=0.023) and loss of appetite (OR=10.30 95% CI 1.04-101.10, p=0.045). Fatigue was unrelated to sex or age, or to the type of cancer, or the treatment category. Fatigue was common among cancer patients on palliative care. The single most powerful independent explanatory factor of fatigue was anaemia, implicating a need for interventional studies.
    Anticancer research 08/2009; 29(7):2569-75. · 1.71 Impact Factor
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    British Journal of Cancer 07/2009; · 5.08 Impact Factor
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    ABSTRACT: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of group IIA phospholipase A2 (PLA2) as a predictor of disease outcome in stage II CRC patients with long-term follow-up. The present study comprises a series of 116 patients who underwent bowel resection for stage II CRC during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with PLA2. Fifty-five percent of all tumors were positive for PLA2. There was no significant correlation between PLA2 expression and age, sex, depth of invasion and lymph node status. In Kaplan-Meier survival analysis, there was a significant (P = 0.010) difference in disease-free survival (DFS) between patients with negative tumors (longer DFS) and those with positive tumors. The same was true with disease-specific survival (DSS), patients with PLA2-negative tumors living significantly longer (P = 0.025). In multivariate (Cox) survival analysis, however, PLA2 was not an independent predictor of DFS or DSS. In subgroup analysis, the right-sided tumors with negative PLA2 staining had remarkably better prognosis (P = 0.010) than PLA2-positive left-sided tumors. Quantification of PLA2 expression seems to provide valuable prognostic information in stage II CRC, particularly in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.
    Annals of Oncology 04/2009; 20(7):1230-5. · 7.38 Impact Factor
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    ABSTRACT: The aim of the study is to assess the value of carbonic anhydrase isozyme IX (CA IX) expression as a predictor of disease-free survival (DFS) and disease-specific survival (DSS) in rectal cancer treated by preoperative radio- or chemoradiotherapy or surgery only. Archival tumour samples from 166 patients were analysed for CA IX expression by three different evaluations: positive/negative, proportion of positivity and staining intensity. The results of immunohistochemical analysis were confirmed by demonstrating CA IX protein in western blotting analysis. Forty-four percent of the operative samples were CA IX positive, of these 34% had weak and 66% moderate/strong staining intensity. In univariate survival analysis, intensity of CA IX expression was a predictor of DFS (P=0.003) and DSS (P=0.034), both being markedly longer in tumours with negative or weakly positive staining. In multivariate Cox model, number of metastatic lymph nodes and CA IX intensity were the only independent predictors of DFS. Carbonic anhydrase isozyme IX intensity was the only independent predictor of DSS, with HR=9.2 for dying of disease with moderate-intense CA IX expression as compared with CA IX-negative/weak cases. Negative/weak CA IX staining intensity is an independent predictor of longer DFS and DSS in rectal cancer.
    British Journal of Cancer 03/2009; 100(6):874-80. · 5.08 Impact Factor
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    ABSTRACT: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to study the prognostic value of nuclear DNA content in stage II CRC of patients with long-term followup. Isolated nuclei from 50 microm-thick paraffin sections of tissue samples from 253 patients with stage II CRC, who had undergone bowel resection at Turku University Central Hospital were cytocentrifuged on slides, stained with Feulgen staining, and DNA was measured using a computer-assisted image analysis cytometry system. Different approaches were applied in analysis of DNA histograms. DNA content did not show any relation with age (p < 0.96), sex (p < 0.35), tumor invasion (p < 0.77), or grade (p < 0.31). Aneuploid DNA content was significantly more frequent in the cancer of the left colon and rectum than the right colon (p = 0.02). S-phase fraction analysis revealed that a higher proportion (62%) of the older patients (>65 years) had high proliferation rates than did the younger patients (p < 0.05). Patients with narrow range histograms had a better disease-free survival (DFS) (narrow range: 70%, wide range: 60% at 10 years). Tumors with >9c nuclei were associated with significantly better DFS and disease-specific survival (DSS) as compared with the patients who did not have >9c nuclei in their tumor samples (p < 0.003 and p < 0.0001, respectively). Multivariate survival (Cox) model showed that only classification of the basic pattern of the histogram [odds ratio OR) = 29.14; 95% confidence interval (CI) 2.350-361.57] (p = 0.009) and recurrence (OR = 165.35; 95% CI 48.42-564.7) (p = 0.0001) proved to be independent predictors of clinical outcome. Our results seem to suggest it truly is possible, by using DNA cytometry, to find groups with different prognosis among stage II cases. Those with a high recurrence rate should be considered for adjuvant chemotherapy.
    Anticancer research 02/2009; 29(1):99-106. · 1.71 Impact Factor
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    ABSTRACT: The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA), in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer.
    Libyan Journal of Medicine 01/2009; 4(4):143-5. · 1.33 Impact Factor
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    ABSTRACT: Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women.
    International Journal of STD & AIDS 05/2008; 19(4):251-8. · 1.00 Impact Factor
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    ABSTRACT: To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).
    Journal of Medical Screening 02/2008; 15(2):97-104. · 2.35 Impact Factor

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5k Citations
920.46 Total Impact Points

Institutions

  • 2014
    • Hospital de Câncer de Barretos
      San Paulo, São Paulo, Brazil
  • 1994–2013
    • University of Turku
      • • Department of Obstetrics and Gynaecology
      • • Department of Oncology and Radiotherapy
      • • Institute of Dentistry
      • • MediCity Research Laboratory
      • • Department of Pathology
      Turku, Western Finland, Finland
  • 1989–2012
    • Turku University Hospital
      • Department of Obstetrics and Gynecology
      Turku, Province of Western Finland, Finland
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 2006–2008
    • Instituto Adolfo Lutz
      San Paulo, São Paulo, Brazil
    • Hospital De Clínicas De Porto Alegre
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 2005–2006
    • University of Campinas
      • Faculty of Medical Sciences
      Conceição de Campinas, São Paulo, Brazil
  • 2003–2006
    • Istituto Superiore di Sanità
      • Department of Infectious, Parasitic and Immune-mediated Diseases
      Roma, Latium, Italy
  • 2002
    • Ljubljana University Medical Centre
      Lubliano, Ljubljana, Slovenia
  • 2001
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
    • Universidade Federal do Rio Grande do Sul
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 1988–2001
    • Università degli Studi di Siena
      • Department of Medicine, Surgery and Neuroscience
      Siena, Tuscany, Italy
  • 1982–2000
    • University of Kuopio
      • • Department of Pathology
      • • Department of Clinical Microbiology
      • • Department of Clinical Nutrition
      • • Department of Neurology
      • • Department of Ophthalmology
      Kuopio, Eastern Finland Province, Finland
  • 1981–2000
    • Kuopio University Hospital
      • • Department of Clinical Pathology
      • • Department of Surgery
      • • Department of Urology
      • • Department of Obstetrics and Gynaecology
      Kuopio, Province of Eastern Finland, Finland
  • 1999
    • German Cancer Research Center
      • Division of Characterization of Tumorviruses
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1995
    • Karolinska University Hospital
      • Department of Dermatology and Venereology
      Stockholm, Stockholm, Sweden
  • 1992–1995
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1993
    • VTT Technical Research Centre of Finland
      Esbo, Southern Finland Province, Finland
  • 1990
    • Helsinki University Central Hospital
      • Department of Obstetrics and Gynaecology
      Helsinki, Province of Southern Finland, Finland