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Paraguay

Cancer Statistics
Population in 2008: 6.2m
People newly diagnosed with cancer (excluding NMSC) / yr: 8,000
Age-standardised rate, incidence per 100,000 people/yr: 166.3
Risk of getting cancer before age 75:17.1%
People dying from cancer /yr: 4,800
Data from IARC GlobalCan (2008)
Paraguay: Cancer Organisations and Resources
Latest Research Publications from Paraguay

Paraguay: Cancer Organisations and Resources (2 links)


Latest Research Publications from Paraguay

Codas M, Pesch B, Adolphs M, et al.
Cancer mortality in Itapúa--A rural province of Paraguay 2003-2012.
Cancer Epidemiol. 2016; 40:1-6 [PubMed] Related Publications
BACKGROUND: Itapúa is a rural department in Paraguay with a population of about 500,000 and a high degree of agro-mechanization for the production of soybean and other crops. So far, only basic health care is provided. Here we analyzed the cancer mortality in this region as a first step towards epidemiological data for cancer prevention.
METHODS: We calculated the age-adjusted mortality rates according to world standard (AMRWs) for the major cancer sites in both males and females between 2003 and 2012, and estimated the differences between the capital and more central districts of Itapúa vs. remote districts.
RESULTS: There were about 2000 cancer deaths in the decade studied, with AMRWs for all malignancies of 90.9/100,000 in males from central vs. 49.1/100,000 in remote districts and 69.0/100,000 vs. 45.0/100,000 in women. Cancer was mentioned in 12.4% of all death certificates and outweighed mortality from certain infectious and parasitic diseases (3.6%). Cause of death was ill-defined in 19.6% of all death certificates, especially in remote regions and among the elderly. The part of cancer located in the uterus (47.8%) or cell type of neoplasm of the lymphatic or hematopoietic system (73.1%) were often not specified. The uterus (mainly the cervix) (C53-C55) was the leading cancer site in women with AMRWs of 17.2/100,000 in central and 14.0/100,000 in remote districts, followed by the breast. Lung and prostate were the leading cancer sites among men. The lung cancer mortality rate was 19.3/100,000 in the central region but 9.5/100,000 in remote districts. Although children comprised 36% of the population, only 24 death certificates listed cancer as cause of death in this decade.
CONCLUSIONS: Analysis of cancer mortality in this rural region of Paraguay, which lacks resources for diagnostics and care, revealed an already large number of cases, with higher rates in the central region than in remote districts. Lung and uterus (primarily the cervix) are common cancer sites and indicate the potential for prevention. However, the quality of the vital statistics needs to be improved. The true cancer burden is most likely underestimated, especially in remote regions and children.

Samudio A, Figueredo D, Lassaletta A, et al.
Building a National Pediatric Cancer Center and Network in Paraguay: Lessons for Addressing Challenges in a Low-income Country.
J Pediatr Hematol Oncol. 2015; 37(5):383-90 [PubMed] Related Publications
In Paraguay, cancer is among the leading causes of death among children. We report challenges and solutions for building the country's first pediatric cancer center at the National University School of Medicine (PCC-SM) and describe the outcomes of the National Network for Pediatric Cancer. We found that children with acute lymphoblastic leukemia treated between 2008 and 2012 had higher 3-year survival rates and lower treatment abandonment rates than did children treated between 2000 and 2007 before the network was established. This improvement directly coincided with the increased treatment capacity of the PCC-SM. Herein, we describe the role of local, national, and international contributors in improving the health care at Paraguay's PCC-SM and discuss how expediting access to specialized cancer diagnosis and care and implementing a system for referral and follow-up visits can improve cancer outcomes in other low-resource countries.

Legal EF, Ascurra M, Custódio G, et al.
Prevalence of an inherited cancer predisposition syndrome associated with the germ line TP53 R337H mutation in Paraguay.
Cancer Epidemiol. 2015; 39(2):166-9 [PubMed] Related Publications
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer, and the germline TP53 R337H mutation is the most common mutation reported to date. However, this mutation is associated with a lower cumulative lifetime cancer risk than other mutations in the p53 DNA-binding domain. A detailed statistical analysis of 171,500 DNA tests in Brazilian neonates found that 0.27% of the general population is positive for this mutation, and some of the estimated 200,000 Brazilian R337H carriers in southern and southeastern Brazil have already developed cancer. The present study was designed to estimate R337H prevalence in neighboring Paraguay. To address this question, 10,000 dried blood samples stored in Guthrie cards since 2008 were randomly selected from the Paraguayan municipalities located at the border with Brazil. These samples were tested for R337H mutation using the PCR-restriction fragment length polymorphism assay. This germline mutation was detected in five samples (5/10,000), indicating that the total number of R337H carriers in Paraguay may be as high as 3500. Previous studies have shown that other countries (i.e., Portugal, Spain, and Germany) presented one family with this mutation, leading us to conclude that, besides Brazil and Paraguay, other countries may have multiple families carrying this mutation, which is an inherited syndrome that is difficult to control.

Mendoza L, Picconi MA, Mirazo S, et al.
Distribution of HPV-16 variants among isolates from Paraguayan women with different grades of cervical lesion.
Int J Gynaecol Obstet. 2013; 122(1):44-7 [PubMed] Related Publications
OBJECTIVE: To determine the distribution of HPV-16 variants among Paraguayan women with different grades of cervical lesions.
METHODS: Sixty-seven HPV-16-positive cervical samples obtained from women attending health centers in Paraguay between March 2007 and April 2009 were examined, including 29 low-grade squamous intraepithelial lesion (LSIL), 29 high-grade squamous intraepithelial lesion (HSIL), 4 cervical cancer, and 5 normal cytology samples. The specimens were analyzed by PCR-directed sequencing of a 364-bp fragment of the long control region of HPV-16, and a phylogenetic tree was compiled with MEGA 5.0 software.
RESULTS: Most HPV-16 variants belonged to the European branch (82%); these variants were detected among 25 of 29 women with LSIL, 22 of 29 women with HSIL, 3 of 4 women with cervical cancer, and all women with normal cytology. Two isolates yielded new variants of the European branch with nucleotide substitutions at positions A7752C and A7810T. Non-European variants, such as African type 1 (1.5%) and Asian-American (16.5%), were detected only among women with cervical lesions (4/29, LSIL; 6/29, HSIL; 1/29, cervical cancer). These variants had at least 6 nucleotide substitutions adjacent to or within transcription factor binding sites.
CONCLUSION: All branches of HPV-16 variants were detected among Paraguayan women with cervical lesions.

Baskin JL, Lezcano E, Kim BS, et al.
Management of children with brain tumors in Paraguay.
Neuro Oncol. 2013; 15(2):235-41 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cure rates among children with brain tumors differ between low-income and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country.
METHODS: Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asunción and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death.
RESULTS: All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities.
CONCLUSIONS: National and center-specific deficiencies in resources to manage pediatric brain tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain tumor programs in other low- and middle-income countries.

Kasamatsu E, Cubilla AL, Alemany L, et al.
Type-specific human papillomavirus distribution in invasive cervical carcinomas in Paraguay. A study of 432 cases.
J Med Virol. 2012; 84(10):1628-35 [PubMed] Related Publications
Cervical carcinoma is the most common malignant tumor among woman in Paraguay. Cytological screening programs have not been successful and a plan for human papillomavirus (HPV) based-screening program and/or vaccination is under evaluation. This study aimed to identify the contribution of HPV genotypes in invasive cervical cancer in Paraguay to provide essential background data to guide and assess the introduction and impact of new preventive strategies based on HPV. Four hundred thirty two histologically confirmed cases (1960-2004) were analyzed. HPV detection in paraffin blocks was performed at the Catalan Institute of Oncology using PCR with SPF-10 broad spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe analysis. The majority of cases were squamous cell carcinoma (92.8%). Mean patients age was 48 years old. HPV DNA was detected in 73.1% of the cases and single infections were predominant (97.8%). The most common HPV single types were 16, 18, 45, 33, 31, 52, 35, and 39. 73.1% of HPV positive cases had an HPV 16, 18 as single infection. HPV16 was frequent in SCC whereas HPV 18 and 45 were prevalent in glandular tumors. Significant decrease of HPV 16 with age groups (P-trend = 0.022) and increase in other HPV types (P-trend > 0.001) were observed. The potential impact of HPV 16 and 18 for a vaccination program was 73.1%. The study provide a profile of the HPV situation in the country, with robust clinical, pathological and virological data which would permit a better cervical cancer screening and vaccination programs.

Andrici J, Eslick GD
Maté consumption and the risk of esophageal squamous cell carcinoma: a meta-analysis.
Dis Esophagus. 2013 Nov-Dec; 26(8):807-16 [PubMed] Related Publications
Maté, a tea-like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta-analysis on the subject has been performed to date. A meta-analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever- vs. never-drinkers), as well as for the dose-dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66-3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33-5.73 vs. OR 1.84, 95% CI 1.12-3.00). Heterogeneity was observed in the ever versus never and the high-consumption analyses but not in the low-consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.

Chaux A, Netto GJ, Rodríguez IM, et al.
Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma.
World J Urol. 2013; 31(4):861-7 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The incidence of penile cancer is four times higher in Paraguay than in the United States or Europe. There are no adequate scientific explanations for this geographical variation. The goal of this study was to evaluate the interplay among risk factors, morphology of the primary tumor, and HPV status.
METHODS: Information on socioeconomic status, education level, habits, and sexual history was obtained in 103 Paraguayan patients with penile cancer. All patients were then treated by surgery, and specimens were evaluated histopathologically.
RESULTS: Patients usually dwelled in rural/suburban areas (82%), lived in poverty (75%), had a low education level (91%), and were heavy smokers (76%). Phimosis (57%), moderate/poor hygienic habits (90%), and history of sexually transmitted diseases (74%) were frequently found. Patients with >10 lifetime female partners had an odds ratio of 3.8 (95% CI 1.1, 12.6; P-trend = .03) for presenting HPV-positive tumors when compared to patients with <6 partners. However, this trend was not significant when the number of sexual partners was adjusted for age of first coitus and antecedents of sexually transmitted diseases. HPV-related tumors (found in 36% of the samples) were characterized by a warty and/or basaloid morphology and high histological grade in most cases.
CONCLUSIONS: In our series, patients with penile cancer presented a distinctive epidemiologic and pathologic profile. These data might help explaining the geographical differences in incidence and aid in the design of strategies for cancer control in Paraguay.

Soskin A, Vieillefond A, Carlotti A, et al.
Warty/basaloid penile intraepithelial neoplasia is more prevalent than differentiated penile intraepithelial neoplasia in nonendemic regions for penile cancer when compared with endemic areas: a comparative study between pathologic series from Paris and Paraguay.
Hum Pathol. 2012; 43(2):190-6 [PubMed] Related Publications
Penile squamous cell carcinoma shows an ample geographic variation in its prevalence with regions of low (North America, Europe, Japan, and Israel) and high (Africa, Asia, and South America) incidence. However, the geographic variation in the distribution of penile intraepithelial neoplasia is not well established. The aim of the present study was to compare the distribution of in situ and invasive lesions between geographic areas with low (France) and high (Paraguay) penile cancer incidence using a series of consecutive cases. The French series included 86 cases (57 in situ and 29 in situ + invasive squamous cell carcinoma), and the Paraguayan series, 117 cases (31 in situ and 86 in situ + invasive squamous cell carcinoma). Incidence of invasive squamous cell carcinoma in the overall samples was higher in the Paraguayan series (P < .00001). Comparing the Paraguayan and the French series, differentiated penile intraepithelial neoplasia was more prevalent in the former (65.0% versus 19.8%), whereas lesions showing warty and/or basaloid features predominated in the latter (35.0% versus 80.2%) to a significant level (P < .00001). This distinctive pattern of differential distribution was maintained when cases with associated invasive squamous cell carcinoma were excluded. The pattern of distribution of lichen sclerosus was also distinctive, with a significantly higher prevalence in the Paraguayan population when compared with the French series (32.5% versus 12.8%, P = .0015). In summary, there appears to be a distinctive distribution of penile precursor lesions depending on the geographic region in consideration. Penile intraepithelial neoplasia with warty and/or basaloid features predominated in low-incidence areas, whereas differentiated penile intraepithelial neoplasia was more prevalent in endemic regions for penile cancer. Further prospective studies in matched populations and from different geographic regions are needed to further clarify the reasons for this discrepancy.

Mendoza LP, Arbiza J, Paez M, et al.
Distribution of human papillomavirus genotypes in Paraguayan women according to the severity of the cervical lesion.
J Med Virol. 2011; 83(8):1351-7 [PubMed] Related Publications
The incidence of cervical cancer in Paraguay is among the highest in the world. This study aimed to determine the distribution of human papillomavirus (HPV) genotypes in Paraguayan women, according to the severity of the cervical lesion. This cross-sectional study included 207 women without a squamous intraepithelial lesion, 164 with low-grade squamous intraepithelial lesions, 74 with high-grade squamous intraepithelial lesions, and 41 with cervical cancer. Type-specific HPV was determined by the polymerase chain reaction with MY9/11 L1 and GP5+/GP6+ L1 primers, followed by restriction fragment length polymorphism and reverse line blotting hybridization, respectively. In total, 12 high-risk and 24 low-risk HPVs types were detected. HPV 16 was the most prevalent, followed by HPV 18 in cervical cancer (14.6%), HPV 31 in high-grade squamous intraepithelial lesions (14.9%), HPVs 58/42 in low-grade squamous intraepithelial lesions (9.1% each), and HPVs 31/58 (2.4% each) in women without squamous intraepithelial lesions. Among 285 positive samples, 24.2% harbored multiple HPV types, being this more prevalent in women with squamous intraepithelial lesions (30.8% in low-grade squamous intraepithelial lesions, 22.5% in high-grade squamous intraepithelial lesions, and 22.0% in cervical cancer) than in women without lesions (9.3%). The higher prevalence of HPV 16 and other high-risk HPVs in women both with and without cervical lesions may explain the high incidence of cervical cancer in Paraguay. This information may be of importance for local decision makers to improve prevention strategies. In addition, these results may be useful as baseline pre-vaccination data for a future virological surveillance in Paraguay.

Chaux A, Tamboli P, Ayala A, et al.
Warty-basaloid carcinoma: clinicopathological features of a distinctive penile neoplasm. Report of 45 cases.
Mod Pathol. 2010; 23(6):896-904 [PubMed] Related Publications
Most penile cancers are squamous cell carcinomas, but there are several subtypes with different clinicopathologic, viral, and outcome features. We are presenting 45 cases of a distinctive morphological variant of penile squamous cell carcinoma composed of mixed features of warty and basaloid carcinomas. This tumor was earlier recognized in a recent viral study and showed a high association with human papillomavirus infection. However, clinicopathologic features are not well known. In this multi-institutional study, patients' mean age was 62 years. Most tumors (64%) invaded multiple anatomical compartments, including glans, coronal sulcus, and, especially, inner foreskin mucosa. Tumor size ranged from 2 to 12 cm (mean 5.5 cm). Three morphological patterns were recognized: (1) the most common, observed in two-thirds of the cases was that of a typical condylomatous tumor on surface and basaloid features in deep infiltrative nests; (2) in 15% of the cases, there were non-papillomatous invasive carcinoma nests with mixed basaloid and warty features; and (3) unusually, predominantly papillomatous. Invasion of penile erectile tissues was frequent, either corpus spongiosum or cavernosum (47% each). Tumors limited to lamina propria were rare. Most tumors were of high grade (89%). Vascular and perineural invasion were found in about one-half and one-quarter of cases, respectively. Associated penile intraepithelial neoplasia was identified in 19 cases and mostly showed basaloid, warty-basaloid, or warty features. Inguinal nodal metastases were found in 11/21 patients with groin dissections. Invasion of corpora cavernosa, high histological grade, and presence of vascular/perineural invasion were more prevalent in metastatic cases. In 21 patients followed, the cancer-specific mortality rate was 33% with a mean survival time of 2.8 years. Warty-basaloid carcinomas are morphologically distinctive human papillomavirus-related penile neoplasms that, such as basaloid carcinomas, are biologically more aggressive than typical warty carcinoma from which they should be distinguished.

Torres LM, Páez M, Insaurralde A, et al.
Detection of high risk human papillomavirus cervical infections by the hybrid capture in Asunción, Paraguay.
Braz J Infect Dis. 2009; 13(3):203-6 [PubMed] Related Publications
Cervical cancer is the most frequent malignant tumour of women in Latin America being human papillomavirus (HPV) the main cause. The aim of this study was to increase the knowledge about the cervical infections with oncogenic HPV types (HR-HPV) in Asuncion, Paraguay. Two hundred and seventy-two cervical samples were analyzed using hybrid capture II assay (HCA II) for HR-HPV. The frequency of HR-HPV in the study group was 44%. HR-HPV was detected in 25% of the women negative for squamous intraepithelial lesions (NSIL), 72% with atypical squamous cells of undetermined significance (ASCUS), 68% with low SIL and 78% with high SIL. A moderate concordance was observed between HCA II assay and cytology (kappa: 0.43 IC(95% 0.3-0.5)). It was detected a high frequency of HR-HPV in women from 11 to 30 years old and in those over 60 years old. The data obtained in this study showed a high frequency of HR-HPV in woman with NSIL and ASCUS, which corroborate that the use of cytology together with HCA II assay for HR-HPV could improve remarkably the efficiency of screening programs of cervical cancer in Paraguay. Furthermore, these findings point out the need for the periodical follow-up of HR-HPV infections in older women.

Cubilla AL, Lloveras B, Alejo M, et al.
The basaloid cell is the best tissue marker for human papillomavirus in invasive penile squamous cell carcinoma: a study of 202 cases from Paraguay.
Am J Surg Pathol. 2010; 34(1):104-14 [PubMed] Related Publications
Human papillomavirus (HPV) has been reported in 12-82% of penile squamous cell carcinomas (SCC). There is an association of the virus with basaloid and warty carcinomas but the reported prevalence is variable. The causes of these variations are not clear. They may be owing to geographic differences, the use of different techniques to detect HPV, the status of the original paraffin blocks, or to variable criteria in tumor classification. The aims of the study were to determine the prevalence of HPV in penile SCC and subtypes using a sensitive technique, to investigate genotypes involved, and to search for other morphologic features associated with the virus from a series of cases from Paraguay. HPV detection was done by SPF-10 polymerase chain reaction followed by DNA enzyme-immunoassay and genotyping by LIPA 25 (version 1). Samples were tested at Catalan Institute of Oncology, Barcelona, and cross testing was carried out at the Delft Diagnostic Laboratories in The Netherlands. HPV was detected in 64 of 202 cases (32%). Thirteen tumors had multiple HPV genotypes. Most prevalent genotypes were HPV-16 (46 cases), HPV-6 (6 cases), and HPV-18 (4 cases), either in single or in multiple infections. HPV was preferentially associated with warty-basaloid (82%), basaloid (76%), and warty (39%) carcinomas and not detected in verrucous, mixed verrucous-papillary, pseudohyperplastic, and pseudoglandular SCCs. There was a strong association between HPV and higher histologic grade. Basaloid cells were more frequently found in HPV positive tumors (72%) and this association was statistically significant in univariate and multivariate analyses. Cells with koilocytotic features and keratinizing squamous cells were also present but to a much lesser degree (47% and 19%, respectively). In summary, HPV was found in a third of the cases and the most common genotype was HPV-16. Low-risk genotypes were rarely found in single infections, representing 4 cases among all analyzed (2%). There was an association between HPV presence and higher histologic grade and with basaloid, warty-basaloid, and warty carcinomas. Our results also suggest that, in penile SCC, the basaloid cell is the best tissue marker for oncogenic HPV infection.

Chaux A, Lezcano C, Cubilla AL, et al.
Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions.
Int J Surg Pathol. 2010; 18(4):268-77 [PubMed] Related Publications
There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.

Chaux A, Reuter V, Lezcano C, et al.
Comparison of morphologic features and outcome of resected recurrent and nonrecurrent squamous cell carcinoma of the penis: a study of 81 cases.
Am J Surg Pathol. 2009; 33(9):1299-306 [PubMed] Related Publications
Penile squamous cell carcinoma (SCC) is considered a loco-regional disease with a fairly predictable pattern of progression. Widespread dissemination occurs in at least one-third of the patients. Local recurrence (defined as the presence of tumor after a primary treatment affecting any remainder tissue, including skin, erectile corpora, or urethra) present in up to 30% of the patients increases the risk of regional inguinal and pelvic lymph nodes metastases. The aim of this study was to identify adverse pathologic prognostic factors in patients with recurrent tumors. Clinicopathologic features of 81 surgically treated patients (25 with recurrent and 56 with nonrecurrent SCC) were evaluated; 56 patients (19 with recurrent and 37 with nonrecurrent tumors) additionally received groin dissections. Follow-up (2 to 372 mo, mean of 71 mo) was obtained in all patients. Comparison of recurrent tumors at the time of the primary diagnosis and of recurrence showed that histologic subtype and grade were identical in 76% of the cases and converted to a higher grade tumor in 24% of the cases, especially, in patients treated with local excisions and circumcisions. Most of the recurrences (67%) seemed at or before 12 months. Comparison of recurrent and nonrecurrent tumors showed that high grade tumors (basaloid and sarcomatoid) tended to be significantly associated with recurrent tumors, whereas low grade variants (papillary, warty and verrucous) were more frequent in the nonrecurrent group; recurrent tumors invaded into deeper anatomic levels than nonrecurrent tumors. The incidence of inguinal lymph node metastasis was higher in recurrent tumors (79% vs. 49%, P=0.0272). Cancer-specific survival was of 46% versus 76% at 3 years of follow-up in recurrent and nonrecurrent tumors, respectively. Patients with recurrent tumors had a median survival of 2.9 years; no major changes in survival were noted after 3 years of follow-up. Mortality was higher in the recurrent group (56% vs. 29%, P=0.0188); 80% of patients with high-grade tumors (basaloid, sarcomatoid, and high grade usual or hybrid verrucous SCCs) died from penile cancer. Mortality in patients with usual SCC was higher in the recurrent group, but similar in basaloid and sarcomatoid SCCs. After 3 years there was no survival difference in patients with low-grade recurrent tumors; however, in the high grade recurrent group there was a progressive and gradual decrease in survival from 2 to 10 years (median survival of 2.5 y). In summary, histologic subtypes and grades of SCCs were similar in the majority of original and recurrent carcinomas. Inguinal metastasis and mortality were higher in recurrent than in nonrecurrent carcinomas. Basaloid, sarcomatoid, and mixed usual-verrucous variants and invasion of corpora cavernosa or preputial skin were significant adverse prognostic factors of recurrent carcinomas. Local excision and partial penectomy were not adequate procedures for sarcomatoid and basaloid penile carcinomas. Carcinomas of foreskin had a better prognosis. Conversion from low to high-grade carcinoma was related to significant mortality. The identification of the adverse prognostic factors found in this study should be the base for an aggressive initial therapy to prevent recurrence in a subset of penile cancers. Re-excision of the recurrent tumor permitted the control of the disease only in one-third of the patients.

Velazquez EF, Cubilla AL
Penile squamous cell carcinoma: anatomic, pathologic and viral studies in Paraguay (1993-2007).
Anal Quant Cytol Histol. 2007; 29(4):185-98 [PubMed] Related Publications
In developed countries, penile squamous cell carcinoma (SCC) account for < 1% of all malignancies in men. It is more frequent in rural populations of Africa, Asia and Latin America, where it may constitute nearly 10% of all carcinomas. In Paraguay, approximately 30-40 new cases are diagnosed per year. Different subtypes of penile carcinomas have been described. Most SCCs are of the usual type (60%). Less frequent variants include basaloid (10%), warty (10%), papillary (15%), verrucous (3%), sarcomatoid (4%) and adenosquamous (1%). Mixed forms also exist. Because there is a correlation between histologic subtype and biologic behavior, accurate subtyping is important. The prevalence of human papillomavirus (HPV) in invasive SCC is approximately 42%, with a strong association of HPV and basaloid and warty variants. Among the most important prognostic factors are histologic grade and depth of invasion. It is important for surgical pathologists to know the anatomy of the penis and possible routes of tumor spread because negative resection margins are crucial to avoid local recurrences. The most frequently involved margins are the urethra and periurethral tissues, including Buck's fascia. Probable precursor lesions of penile carcinoma include squamous hyperplasia, low and high grade squamous intraepithelial neoplasia and lichen sclerosus.

Castellsagué X, Muñoz N, De Stefani E, et al.
Influence of mate drinking, hot beverages and diet on esophageal cancer risk in South America.
Int J Cancer. 2000; 88(4):658-64 [PubMed] Related Publications
To estimate the effects of consuming hot beverages, including mate (an infusion of the herb Ilex paraguayensis), tea, coffee and coffee with milk, and other food items on esophageal cancer risk, we analyzed data from 830 cases and 1,779 controls participating in a series of 5 hospital-based case-control studies of squamous-cell carcinoma of the esophagus conducted in high-risk areas of South America. After adjusting for the strong effects of tobacco and alcohol consumption, both heavy mate drinking (>1 l/day) and self-reported very hot mate drinking were significantly associated with esophageal cancer risk in men and women. The magnitude and strength of the association for mate amount and, to a lesser extent, mate temperature were higher for women than men. The joint effects of mate amount and mate temperature were more than multiplicative, following a statistically significant synergistic interaction (p = 0.02) which was particularly evident among heavy drinkers (>1.50 l/day) of very hot mate (odds ratio = 4.14, 95% confidence interval: 2.24-7.67) compared to light drinkers (<0.50 l/day) of cold/warm/hot mate. Consumption of other very hot beverages, such as tea and coffee with milk but not coffee alone, was also significantly associated with an increased risk, in the 2- to 4-fold range. Statistically significant protective associations were identified for high consumption of vegetables, fruits, cereals and tea. In contrast, frequent consumption of meat, animal fats and salt was associated with a moderately increased risk. This pooled analysis adds evidence for a carcinogenic effect of chronic thermal injury in the esophagus induced by the consumption of very hot drinks, including mate. Our study further confirms the protective effect of a dietary pattern characterized by daily consumption of fruits and vegetables and low consumption of meat and animal fats.

Rolón PA, Smith JS, Muñoz N, et al.
Human papillomavirus infection and invasive cervical cancer in Paraguay.
Int J Cancer. 2000; 85(4):486-91 [PubMed] Related Publications
HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case-control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case-control study conducted in Asunción, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One-hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age-matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR-based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36-361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58.

Castellsagué X, Muñoz N, De Stefani E, et al.
Independent and joint effects of tobacco smoking and alcohol drinking on the risk of esophageal cancer in men and women.
Int J Cancer. 1999; 82(5):657-64 [PubMed] Related Publications
To estimate the independent and joint effects of tobacco smoking and alcohol drinking, we analyzed data from a series of 5 hospital-based case-control studies of squamous-cell carcinoma of the esophagus conducted in high-risk areas in South America. A total of 830 case subjects and 1779 control subjects were included in the pooled analysis. All exposure characteristics of amount, duration, cessation and type of alcohol and tobacco consumed were strongly related to esophageal-cancer risk in both sexes. Women had the same exposure profile as men, but the magnitudes of the associations were lower than were those among men. Black-tobacco smoking was associated with a 2-fold increased risk as compared with the smoking of blond or mixed tobacco. Quitting either of the 2 habits significantly reduced esophageal-cancer risk. Alcohol and tobacco alone were strongly related to the risk of esophageal cancer, even in the absence of the other exposure. A history of simultaneous exposure to cigarette smoking and alcohol drinking had a strong multiplicative effect on risk. Concomitant exposure to heavy alcohol drinking and black-tobacco smoking identified the group with the highest risk for developing esophageal cancer (odds ratio = 107). A synergistic interaction was found between the 2 habits, particularly in women and in moderately exposed men. Moderate cigarette smoking without drinking and moderate alcohol drinking without smoking had a negligible effect on esophageal-cancer risk. However, simultaneous exposure to the same moderate amounts increased the risk 12- to 19-fold in men and in women respectively. The overall public-health implications of these findings are obvious for a tumor that depends on preventive strategies for its control.

Love JL, Marchioli CC, Dube S, et al.
Expansion of clonotypic T-cell populations in the peripheral blood of asymptomatic Gran Chaco Amerindians infected with HTLV-IIB.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 18(2):178-85 [PubMed] Related Publications
Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction (PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses were performed using primer pairs designed to identify expanded T-cell familial clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB-positive samples tested, five showed evidence of V-beta clonotypic T-cell expansion. Of the five expansions, two were monoclonotypic and the remaining three were oligoclonotypic. In comparison, 30 HTLV-II-negative Amerindians showed no evidence of clonotypic T-cell expansion. Amplified DNA from one of the monoclonotypic samples was subsequently cloned and sequenced and was found to have uniform variable/ diversity/joining sequences confirming its unique monoclonal T-cell expansion. This method of detecting clonal TCR beta gene rearrangements has the advantage over traditional Southern blot techniques of being more sensitive and specific even with suboptimal specimens. The prognostic significance of clonotypic T-cell expansion in a group such as the HTLV-II-infected Gran Chaco Amerindians remains to be determined.

Rolón PA, Kramárová E, Rolón HI, et al.
Plantar melanoma: a case-control study in Paraguay.
Cancer Causes Control. 1997; 8(6):850-6 [PubMed] Related Publications
In Paraguay, the plantar surface of the foot is the most common site for malignant melanoma, as it is in several other populations worldwide, most notably in those of African descent. Here, we report the results of the first case-control study of plantar melanoma, carried out in Paraguay. Sixty incident, histologically confirmed cases of plantar melanoma and 256 hospital controls were recruited in 11 hospitals throughout the country during 1988-93. Information was collected on general demographic, social, and lifestyle variables, on external exposures of feet (shoewear, work activities, injuries), and on some constitutional factors (skin, eye and hair color, and pigmented lesions of the feet). Few of the factors examined appeared to be associated with the risk of plantar melanoma. Adjusted for possible confounders, the strongest association was found for reported injuries (odds ratio [OR] = 40.9, 95 percent confidence interval [CI] = 14.8-112.7) and for occurrence of naevi on the soles (OR = 5.9, CI = 2.5-14.3). Walking barefoot did not seem to contribute to the risk although an outdoor workplace was associated with an increased melanoma occurrence (OR = 2.3, CI = 1.1-4.8). Future studies should be aware of problems of recall bias with respect to previous injuries, and ensure that evaluation of pigmentation of the sole is carried out blind to case/control status.

Rolón PA, Castellsagué X, Benz M, Muñoz N
Hot and cold mate drinking and esophageal cancer in Paraguay.
Cancer Epidemiol Biomarkers Prev. 1995; 4(6):595-605 [PubMed] Related Publications
A hospital-based case-control study, including 131 cases of esophageal cancer and 381 controls, was carried out in Paraguay to investigate the role of hot and cold mate drinking in esophageal cancer risk. Detailed information on mate drinking and on tobacco smoking, alcohol consumption, and dietary habits was obtained by interview. Amount and duration of cold or hot mate drinking were not associated with esophageal cancer risk. However, temperature at which mate was drunk was significantly associated with risk. As compared to drinkers of warm or hot mate, drinkers of very hot mate had an increased risk for esophageal cancer even after adjusting for the strong effects of alcohol and tobacco consumption (adjusted odds ratio = 2.4; 95% confidence interval = 1.3-4.3). This effect seemed to be mainly due to the temperature at which mate cocido (one of the two ways in which hot mate is prepared) was drunk (odds ratio = 6.5; 95% confidence interval = 3.2-12.2). As expected, very strong dose-response associations were found for alcohol consumption and cigarette smoking. After correcting for these and the consumption of other food groups, diets rich in fats and red meats, especially beef, were associated with esophageal cancer risk. In conclusion, the findings from this study suggest that cold mate drinking does not increase the risk of esophageal cancer. This study identifies the very hot temperature at which mate is drunk, and not the amount or the duration, as an important risk factor for esophageal cancer in this population. Alcohol drinking and tobacco smoking remain, nevertheless, the main risk factors for esophageal cancer in Paraguay.

Rolon PA, Hochsztajn B, Llamosas F
Epidemiology of complete hydatidiform mole in Paraguay.
J Reprod Med. 1990; 35(1):15-8 [PubMed] Related Publications
The incidence of complete hydatidiform mole in Paraguay is 0.23-0.25 cases per 1,000 pregnancies. The incidence is as high at the extremes of reproductive age as at other ages. That finding is at variance with long-accepted concepts. The incidence in the 15- to 19-year age group is lower than earlier, with a greater use of contraceptives in the older group. Complete mole is a rare condition with a high incidence in certain geographical areas.

Rolon PA, Hochsztajn de Lopez B
Malignant trophoblastic disease in paraguay.
J Reprod Med. 1979; 23(2):94-6 [PubMed] Related Publications
The incidence of malignant trophoblastic diseases from 1960 to 1969 and 1970 to 1974 in the population of Parguay was low, as shown by the analysis of unselected hospital admissions as compared to the total population. Paraguay showed disease characteristics comparable to those of developing countries where malignant diseases of the trophoblast have elevated frequencies. The apparently high frequencies in lower socioeconomic groups appear to be due to the fact that these groups make up a large proportion of the hospital population. The hardship of poverty predisposes to the hospital concentration of pathologic pregnancies from around the country and to the home delivery of grossly normal gestations. Thus, a biased incidence of diseases results.

Rolón PA, de Lopez BH
Epidemiological aspects of hydatidiform mole in the Republic of Paraguay (South America).
Br J Obstet Gynaecol. 1977; 84(11):862-4 [PubMed] Related Publications
A total of 227 hydatidiform moles was recorded in Paraguay over a 10-year period (1960 to 1969). Using demographic studies, the annual incidence of hydatidiform moles was calculated as 0.229 per 1000 pregnancies or 1 per 4369 pregnancies, with the highest incidence occurring at the extremes of reproductive life.

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