Molecular variant analysis as an epidemiological tool to study persistence of cervical human papillomavirus infection.
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Cytopathogenic Effect, Viral↗
Biomedical subjects
E L Franco
Publications and source records attributed to E L Franco.
A randomized clinical trial of single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Results after extended follow-up. Brazilian Wilms' Tumor Study Group.
BACKGROUND: To verify the adequacy of a simplified chemotherapeutic regimen for the treatment of Wilms' tumor (WT), the authors conducted a clinical trial to compare the standard fractionated dose (15 mcg/kg x 5 days) of dactinomycin (AMD) with a single dose (60 mcg/kg x 1 day) administration of the drug. METHODS: From October 1986 to December 1988, 176 WT patients were enrolled in a randomized, multicentric clinical trial conducted by the Brazilian WT Study Group in 38 institutions from 8 states. Patients were randomly assigned to treatment arm A (standard 5-day fractionated AMD administration) or arm B (single high dose AMD administration) in the schedules most appropriate for their stage and histology. Except for the differences in AMD administration, patients were managed by the Third U.S. National WT Study protocol. The endpoints of interest were relapse free and overall survival. Complete follow-up information was obtained until December 1992. RESULTS: After a median follow-up of 47 months, there were no significant differences in survival distributions between treatment arms, using data for all patients or data stratified by disease stage. Relapse free and overall 4-year rates were similar in both groups: 67% and 72%, respectively, in arm A, and 67% and 75%, respectively, in arm B (P = 0.839 and 0.710, respectively). Patients assigned to the simplified arm had cumulatively 1921 fewer hospital days as compared with those receiving the fractionated dose. Hepatic toxicity was observed in only one patient assigned to the divided dose regimen and in none of the single dose group. CONCLUSIONS: WT can be treated using a single dose regimen for AMD administration, thus minimizing the inconvenience for the children and their parents and reducing considerably health care delivery costs.
Child, Preschool↗
Correspondence re: B. Fernandes et al., beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. Cancer Res., 51: 718-723, 1991.
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Biomarkers, Tumor↗
Lateness of diagnosis of oral and oropharyngeal carcinoma: factors related to the tumour, the patient and health professionals.
The risk of presenting with advanced stage vs. early stage disease was evaluated in a prospective study of 336 consecutive patients with oral and oropharyngeal carcinomas referred to three head and neck surgery services in Sao Paulo, Curitiba and Goiania during the period from February 1986 to December 1988. Income and educational levels were not associated with stage distribution. The risk of having advanced disease was dependent upon male gender. Another important determinant of advanced stage was tumour location on the less visible surfaces of the oral cavity and oropharynx. Although there was a clear increase in delay of referral among cases who were seen by more than one health professional, duration of symptoms and patient and professional delays were not associated with the risk of advanced disease in unifactorial analysis. The following factors were independently associated with the risk of advanced disease for lip carcinoma: a painful ulcer, alcoholism and delay caused by a non-specialist medical doctor. The risk factors associated to advanced oral carcinoma were: type of lesion, odynophagia/dysphagia, delay caused by a dentist and delay caused by a non-specialist medical doctor. Two of the most important immediate consequences of advanced stage were a conspicuous increase in treatment costs and a longer hospital stay.
Adolescent↗
Maté, coffee, and tea consumption and risk of cancers of the upper aerodigestive tract in southern Brazil.
Consumption of maté, a tea-like infusion of the herb Ilex paraguariensis, is common in South America. Drinkers have high risks of upper aerodigestive tract cancers, but it is conceivable that this high risk may be attributable to confounding by smoking alcohol, and other exposures. To test this hypothesis, we analyzed the data from a case-control study of upper aerodigestive tract cancers conducted in Southern Brazil. We matched noncancer controls (N = 756) to cases (N = 378) on the basis of age, sex, and period of admission. We estimated the effect of mateé consumption by conditional logistic regression with adjustment for smoking, alcohol, sociodemographics, and several dietary items, considered as confounders. The unadjusted relative risk (RR) for all upper aerodigestive tract cancers was 2.1 [95% confidence interval (CI) = 1.6-2.7]. Some excess risk persisted after adjustment for potential confounders (RR = 1.6; 95% CI = 1.2-2.2). Most of the excess risk for maté drinkers was for oral (RR = 1.9; 95% CI = 1.1-3.3) and laryngeal (RR = 2.2; 95% CI = 2.2; 95% CI = 1.1-4.5) cancers. There was no evidence of associations with coffee and tea drinking. We conclude that the association of maté consumption with upper aerodigestive tract cancer risk is unlikely to result from insufficient control of confounding by critical exposures. Owing to its high prevalence in Southern South America, maté drinking may be linked to as many as 20% of all cases occurring in this region.
Aged↗
Association between timing of surgery during menstrual cycle and prognosis in pre-menopausal breast cancer.
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Adult↗
Race and gender influences on the survival of patients with mouth cancer.
Previous studies have shown that race and gender are important correlates of survival among patients with cancer of certain sites. Since race and gender influence the stage of disease at diagnosis and the choice of therapy it has been argued that survival differentials may not be real but instead, they represent secondary associations with clinical variables. Therefore, verification of the true prognostic effects of race and gender requires proper controlling for potential confounders, such as stage and treatment. We have studied the 15-year survival experience of a hospital-based cohort of 4527 patients diagnosed with cancer of the mouth over a 28-year period in Brazil. Race and gender were strong predictors of stage and treatment. The odds ratios for no treatment were 1.35 (95% confidence limits [CL]: 1.09, 1.66) for females and 1.63 (CL: 1.29, 2.06) for non-white patients even after adjustment by stage, presumably a key criterion to define treatment. Survival differentials were found for lip cancer, with respect to race, and for cancers of the gum, floor of mouth, and other oral subsites, with respect to gender. Non-whites experienced 2.1 times the risk of lip cancer recurrence (CL: 1.20, 3.61) and 2.3 times the risk of dying from it (CL: 1.29, 4.09) as compared to whites. However, controlling for stage and treatment modality variables by proportional hazards regression reduced the same risk ratios to 1.01 (CL: 0.57, 1.78) and 1.17 (CL: 0.65, 2.13), respectively. The survival advantage experienced by females (17% lower risk of recurrences and 29% lower risk of cancer deaths) regarding other oral sites was independent from the effect of clinical factors.
Adult↗
Measurement errors in epidemiological studies of human papillomavirus and cervical cancer.
Measurement errors have been an important concern in studies of human papillomavirus (HPV) and anogenital cancers. Misclassification of HPV infection status is a possible explanation for incoherent findings in previous epidemiological studies purporting to show an etiological role for HPV in cervical cancer. Even low levels of misclassification of HPV infection can cause severe underestimation of HPV prevalence in field surveys, bias the association between HPV and sexual activity, and impair the ability to control statistically the relation between sexual activity and neoplasia by viral status. The present report focuses on aspects that have not been elaborated in two previous studies (Kaldor, 1989; Franco, 1991). Emphasis is given to effects of measurement errors of HPV infection status in biasing the association with cervical neoplasia under more complex scenarios, e.g., differential misclassification between cases and controls in a case-control study, and non-differential misclassification of both viral infection and cervical neoplasia in cross-sectional cytology surveys and cohort studies. Some simple numeric formulae are given that allow the correction of prevalence rates and epidemiological measures of effect, such as the odds ratio and the relative risk, under the latter conditions of misclassification constraint. These formulae have been used to correct estimates from recent epidemiological studies using hypothetical misclassification scenarios in order to obtain clues on the magnitude of the underlying relationship between HPV and cervical cancer.
Bias↗
Epidemiological and clinical correlations with genetic characteristics of Wilms' tumor: results of the Brazilian Wilms' Tumor Study Group.
The epidemiological and clinical features of Wilms' tumor (WT) were analyzed in 176 patients admitted to the Brazilian WT Study Group. The occurrence of congenital anomalies (9.1%) and the M:F ratio (0.83) were comparable to those observed by the US National WT Study and the International Society of Pediatric Oncology trials. Bilateral cases were younger on average than unilateral cases (37.2 vs. 45.0 months). Ethnic group and gender were also associated with age, with non-white children being generally older (46.1 months) than whites (39.5 months), and boys being younger than girls (37.0 vs. 46.1 months). However, the most important factor in association with age at diagnosis was disease stage. No early disease patients were diagnosed after 8 years of age (mean: 37.5 months), whereas 10% of those with advanced disease were diagnosed between the ages of 8 and 10 years (mean: 56.3 months). There were no clear distinctions in age distributions on the basis of the presence of tumor multicentricity, intra- or perilobar nephroblastomatosis, and of a combination of putative genetic determinants. The mean age at diagnosis for cases with congenital defects was higher than that for the remaining patients. Some of the study results are in support of the recessive oncogene model for WT. However, the possible confounding effect of disease stage and the strong interdependence of the remaining factors may be masking important relations in regard to mutational events occurring during embryogenesis.
Age Factors↗
Single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Preliminary results of a clinical trial. The Brazilian Wilms' Tumor Study Group.
A clinical trial was conducted by the Brazilian Wilms' Tumor (WT) Study Group to compare the single-dose (60 micrograms/kg x 1 day) administration of dactinomycin (AMD) with the standard fractionated dose (15 micrograms/kg/d x 5 days) used in the US National WT Study. Except for the AMD administration, treatment for all patients followed that of the latter study. Patients were randomized to receive either of the two AMD regimens in the schedules most appropriate for their stage and histologic condition. One hundred seventy-six children with WT entered the study until December 1988. No significant differences in overall or relapse-free survival distributions were observed between treatment arms using data for all patients or data stratified by disease stage. Two-year survival rates were 83.0% and 85.3% for patients receiving the fractionated and single doses of AMD, respectively. Survival distributions could also be compared once patients with protocol violations were excluded. The overall 2-year survival rates were 89.7% and 88.6% and the relapse-free 2-year survival rates were 78.2% and 76.1% for the fractionated and single AMD doses, respectively. Altered liver function was seen in three patients who received fractionated dose and in four patients who received the single AMD dose. Acute toxicity was observed in only one patient of the fractionated-dose group and in zero of the patients of the single-dose group. At the closing date, patients assigned to the simplified AMD regimen had accumulated 1840 days less of hospital stay than those treated by the standard regimen.
Child↗
Prognostic factors in laryngeal cancer patients submitted to surgical treatment.
The authors studied some demographic, clinical, pathologic, and therapeutic variables in relation to the disease-free interval (DFI) and to the overall survival of laryngeal cancer patients. The patient population consisted of 278 consecutive cases of primary laryngeal cancer who had been admitted to four head and neck surgery services in Sao Paulo and Curitiba (Brazil) between 1973 and 1986. All patients had surgical treatment. Although several variables exhibited individual associations with survival, only a few were deemed to have independent prognostic value using multivariate regression techniques based on Cox's proportional hazards model. The primary tumor stage (T index) represented the variable with the highest predictive strength with respect to survival. Hazard ratios for the risk of disease recurrence were 2.3 (T2-3 vs. T1) and 4.3 (T4 vs. T1). Hazard ratios for the risk of death were 1.6 (T2-3 vs. T1) and 3.3 (T4 vs. T1). The following additional factors were also independently associated with the DFI: age, site of primary tumor (transglottic, glottic, or supraglottic), extracapsular spread of lymph node metastasis, surgical margins, type of paratracheal node dissection, and prior tracheostomy. Except for extracapsular spread, the same factors related to the DFI were also significantly related to the overall survival. Race, sex, N-stage, vascular embolization, and histological grade were other independent predictors of the risk of death.
Aged↗
Multiple cancers of the upper aero-digestive tract: the challenge of risk factor identification.
Carcinomas of the upper aero-digestive tract (UADT) are among the most common neoplasms, particularly in developing countries. The generally poor prognosis for UADT cancer patients is further complicated by the occurrence during follow-up of additional cancers of the same or related sites. Proper quantification of the incidence of these second cancers and characterization of their risk factors have been plagued with methodological difficulties. The effects of tobacco and alcohol consumption vary with anatomic site, which requires that matching or adjustment by site be performed in any comparisons between single primary and multiple primary patients. Clinical variables, such as disease extension, treatment and survival, also influence risk of second malignancies. However, these parameters are also strongly interrelated, which makes it difficult to characterize their individual associations with risk or to control for their confounding effects when examining other variables. These shortcomings should be taken into consideration in the design of studies searching for genetic and other inter-individual variations in susceptibility to multiple UADT malignancies.
Head and Neck Neoplasms↗
Risk factors for second cancers of the upper respiratory and digestive systems: a case-control study.
A case-control study of determinants of multiple cancers of the upper respiratory and digestive system (URDS) was conducted using a patient cohort-nested design. We analyzed demographic and risk factor information and clinical variables related to the index cancer for 85 cases of multiple cancers and 170 controls matched on sub-site of the index cancer of the case and date of hospital admission. Follow-up information for the control group was used to infer the person-years-at-risk for the cohort of 1977 patients. URDS cancer patients experienced a 10.7 times (95% confidence interval: 8.5-13.2) higher risk of additional related cancers than the general population. Although controls had cancers of the same sites as those of cases and thus, strongly tobacco and alcohol-related, there were marked residual effects for these two risks factors. In addition, characteristics related to the extension and clinical course of the index cancer were strongly associated with the patient's risk of developing additional cancers.
Adult↗
The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomavirus infection.
The definition of cervical neoplasia as a sexually determined disease caused by some types of human papillomavirus has been widely accepted. Recent epidemiologic studies, however, have failed to identify a correlation between sexual activity and human papillomavirus infection. Moreover, sexual activity has also been shown to be independent of human papillomavirus infection in increasing cervical cancer risk. These incoherences are analyzed with respect to etiologic models for cervical neoplasia and by considering the role of misclassification of human papillomavirus infection in interpreting the relations assumed under these models. Even small levels of misclassification can considerably distort (1) the presumed prevalence of viral infection, (2) the association between sexual activity and human papillomavirus infection, and (3) the ability to control the relation between sexual activity and cancer by human papillomavirus infection. In field surveys, the presumed rates of human papillomavirus infection based on a DNA assay such as the filter in situ hybridization may be a gross overestimation of the true viral prevalence. Use of moderately misclassified human papillomavirus infection test results for effect estimation and covariate adjustment in data analysis may seriously distort the underlying relations. Consequently, considering these conditions, the apparent incoherence of recent epidemiologic findings should not be construed as evidence against the role of human papillomavirus in the etiology of cervical cancer or the validity of the sexually transmitted disease model.
Adolescent↗
Independent prognostic value of laminin receptor expression in breast cancer survival.
We studied the possible prognostic role of laminin, estrogen (ER), and progesterone (PR) receptors and other pathological factors in relation to the disease-free interval and overall survival of female breast carcinoma patients. Multivariate analyses of clinical and pathological data with respect to the above survival time variables were performed by Cox regression. The statistical dependence of prognosis on ER, PR, and tumor size was based on the discriminant cutoff value that could best distinguish between survival curves. Axillary nodal status was the most significant independent factor in the prediction of both disease-free interval and overall survival of these patients. Use of the information on laminin receptor expression, PR concentration, tumor size, lymphocytic infiltrate, and tumor necrosis improved significantly the prediction of the risk of recurrence. Patients with tumors expressing laminin receptors had 40% less risk of recurrence (P = 0.0209) than those with no expression. On the other hand, four covariates were independently predictive of the risk of death: axillary nodal status, lymphocytic infiltrate, PR and ER concentration. There was a marginally significant (10% level) interaction between tumor size and lymphocytic infiltrate with respect to the prediction of the risk of recurrence. The above sets of variables were used to classify patients into risk groups for the prediction of recurrence and death.
Breast Neoplasms↗
Microcomputer-assisted multivariate survival data analysis using Cox's proportional hazards regression model.
We describe a microcomputer program (COXSURV) for proportional hazards multiple regression analysis of survival and other failure-time data generated in clinical trials and in retrospective clinical epidemiology studies. COXSURV is menu-driven and has powerful variable factoring and data exploratory capabilities for multivariate modeling. A batch mode allows automatic uni- or multivariate analyses for confounder summarization. Model selection for predictive purposes is possible through a step-up algorithm. The partial likelihood method used in the program allows the use of either discrete or continuous time scales by treating tied uncensored observations by either the exact method or by a robust approximation method. The program calculates most standard model fitting statistics for either overall or stratified analyses and uses data layout files compatible with those of other related epidemiologic analysis software.
Algorithms↗
Diagnostic performance indices for immunofluorescent tests and enzyme immunoassays of leishmaniasis sera from northern and north-eastern Brazil.
A total of 341 sera were screened for anti-Leishmania IgA, IgG, and IgM antibodies by immunofluorescent (IF) tests and enzyme immunoassay (ELISA). Altogether, 292 of the sera originated from patients with clinically as well as parasitologically diagnosed (positive lesion imprint or the Montenegro skin test) cutaneous leishmaniasis; 49 of the sera were from controls from the same base population. In terms of diagnostic performance, the ELISAs for IgG and IgM yielded indices of diagnostic utility, and the positive predictive value for the IgG-ELISA was 94.6%. A remarkably high specificity (100%) was obtained with the IgA-IF test, but its sensitivity was very low.
Adolescent↗
Risk factors for oral cancer in Brazil: a case-control study.
A case-control study of risk factors for carcinomas of the tongue, gum, floor, and other specified parts of the mouth was conducted in 3 metropolitan areas in Brazil: São Paulo (southeast), Curitiba (south), and Goiânia (central-west). We analyzed information on demographics, occupational history, environmental exposures, tobacco smoking and alcohol drinking habits, as well as diet, oral and other health characteristics obtained from interviews with 232 cases and 464 hospital non-cancer controls matched for 5-year age-group, sex, hospital catchment area and trimester of admission. Tobacco and alcohol consumption were the strongest risk factors irrespective of the anatomical site. The adjusted relative risks (RR) for ever vs. never smokers were: 6.3, 13.9, and 7.0, for industrial-brand cigarettes, pipe, and hand-rolled cigarettes, respectively. A strong correlation was seen between number of pack-years and risk. The RR for the heaviest vs. the lowest consumption categories (greater than 100 vs. less than 1 pack-years) was 14.8. Risk levels generally decreased to those of never smokers after 10 years had elapsed since stopping smoking. The risk associated with alcohol was mostly evident for wine (cancer of the tongue) and "cachaça" (all sites), a hard liquor distilled from sugar cane. Other important risk factors were drinking "chimarrão" (a type of maté), use of a wood stove for cooking, and frequent consumption of charcoal-grilled meat and manioc. Oral hygiene characteristics represented correlates of disease risk. A significant protective effect was observed for consumption of carotene-rich vegetables and citric fruits, but not for green vegetables in general.
Age Factors↗