Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America : the ESTAMPA screening study protocol

Q1Q1Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659Revista Internacional - Indexad

Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix

Fil: Picconi, María Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: Alonio, Lidia V. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: García Carrancá, Alejandro. Universidad Nacional Autónoma de México. Departamento de Biología Molecular; México.Fil: Lizano, Marcela. Instituto Nacional de Cancerología; México.Fil: Cervantes Vazquez, Guadalupe. Instituto Nacional de Cancerología; México.Fil: Distéfano, Angélica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: Mural, Juan. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Bazan, Juan. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Teyssie, Angelica R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Los virus Papiloma humano (HPV), en particular los tipos 16 y 18, son considerados carcinógenos humanos, habiéndose demostrado una asociación etiológica entre la infección con estos virus y el desarrollo del cáncer de cuello uterino. El rol viral en el carcinoma escamoso ha sido ampliamente estudiado aunque la información disponible en relación al adenocarcinoma es mucho menor, en parte debido a su baja frecuencia. En este trabajo investigamos la presencia de tipos y variantes intratípicas de HPV en adenocarcinomas de cérvix. Se incluyeron 23 biopsias de archivo, fijadas y embebidas en parafina. La detección y tipificación viral se llevó a cabo mediante PCR genérica y posterior análisis de polimorfismos conformacionales de cadena simple (SSCP). La variabilidad genética se investigó en un fragmento de 450 pb del gen L1, mediante la secuenciación directa post-PCR. Se detectaron 11 muestras positivas para HPV 16 (9 prototipos y 2 variantes: 1 europea y 1 asiática-americana), 10 para HPV 18 (9 prototipos y 1 variante europea), 1 para HPV 31 y 1 negativa. Se confirmó la asociación de HPV de alto riesgo con esta neoplasia, con una alta prevalencia (43%) de HPV 18 pero sin un predominio sobre los demás tipos virales, como fue publicado previamente. La variabilidad demostrada en epítopes de la proteína L1 originaron cambios aminoacídicos que podrían tener implicancias en la repuesta inmune y por lo tanto ser considerados en el diseño de vacunas. Human Papillomavirus (HPV), particularly types 16 and 18, are considered human carcinogens since an etiological association has been demonstrated between these viruses and the development of cervical cancer. While the viral role in squamous carcinoma has been largely studied, the information available on adenocarcinoma is scarce, partly because of its lower frequency. In this paper we investigated the presence of HPV types and intratype variants in adenocarcinomas of the cervix. A total of 23 archive samples, fixed and paraffin embedded biopsies, were included. The detection and viral typing was performed by generic PCR and subsequent single stranded conformational polymorphism analysis (SSCP). Genetic variability was investigated in a 450 bpfragment corresponding to L1 gene by post-PCR direct sequencing. We detected 11 HPV 16 positive samples (9 prototypes and 2 variants: 1 European and 1 Asiatic-American), 10 HPV 18 (9 prototypes and 1 European variant), 1 HPV 31 and 1 negative. The high risk HPV association with this neoplasia was confirmed with a high prevalence (43%) of HPV 18, (but) without predominance over the other types as previously published. The demonstrated variability in L1 protein epitopes originated aminoacidic changes which could have implications on the immune response and therefore should be considered in a vaccine design

Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix

Fil: Picconi, María Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: Alonio, Lidia V. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: García Carrancá, Alejandro. Universidad Nacional Autónoma de México. Departamento de Biología Molecular; México.Fil: Lizano, Marcela. Instituto Nacional de Cancerología; México.Fil: Cervantes Vazquez, Guadalupe. Instituto Nacional de Cancerología; México.Fil: Distéfano, Angélica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Fil: Mural, Juan. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Bazan, Juan. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Teyssie, Angelica R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología; Argentina.Los virus Papiloma humano (HPV), en particular los tipos 16 y 18, son considerados carcinógenos humanos, habiéndose demostrado una asociación etiológica entre la infección con estos virus y el desarrollo del cáncer de cuello uterino. El rol viral en el carcinoma escamoso ha sido ampliamente estudiado aunque la información disponible en relación al adenocarcinoma es mucho menor, en parte debido a su baja frecuencia. En este trabajo investigamos la presencia de tipos y variantes intratípicas de HPV en adenocarcinomas de cérvix. Se incluyeron 23 biopsias de archivo, fijadas y embebidas en parafina. La detección y tipificación viral se llevó a cabo mediante PCR genérica y posterior análisis de polimorfismos conformacionales de cadena simple (SSCP). La variabilidad genética se investigó en un fragmento de 450 pb del gen L1, mediante la secuenciación directa post-PCR. Se detectaron 11 muestras positivas para HPV 16 (9 prototipos y 2 variantes: 1 europea y 1 asiática-americana), 10 para HPV 18 (9 prototipos y 1 variante europea), 1 para HPV 31 y 1 negativa. Se confirmó la asociación de HPV de alto riesgo con esta neoplasia, con una alta prevalencia (43%) de HPV 18 pero sin un predominio sobre los demás tipos virales, como fue publicado previamente. La variabilidad demostrada en epítopes de la proteína L1 originaron cambios aminoacídicos que podrían tener implicancias en la repuesta inmune y por lo tanto ser considerados en el diseño de vacunas. Human Papillomavirus (HPV), particularly types 16 and 18, are considered human carcinogens since an etiological association has been demonstrated between these viruses and the development of cervical cancer. While the viral role in squamous carcinoma has been largely studied, the information available on adenocarcinoma is scarce, partly because of its lower frequency. In this paper we investigated the presence of HPV types and intratype variants in adenocarcinomas of the cervix. A total of 23 archive samples, fixed and paraffin embedded biopsies, were included. The detection and viral typing was performed by generic PCR and subsequent single stranded conformational polymorphism analysis (SSCP). Genetic variability was investigated in a 450 bpfragment corresponding to L1 gene by post-PCR direct sequencing. We detected 11 HPV 16 positive samples (9 prototypes and 2 variants: 1 European and 1 Asiatic-American), 10 HPV 18 (9 prototypes and 1 European variant), 1 HPV 31 and 1 negative. The high risk HPV association with this neoplasia was confirmed with a high prevalence (43%) of HPV 18, (but) without predominance over the other types as previously published. The demonstrated variability in L1 protein epitopes originated aminoacidic changes which could have implications on the immune response and therefore should be considered in a vaccine design

Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

The tumour microenvironment plays a vital role in the development of solid malignancies. Here we describe an in vitro human prostate cancer microtissue model that facilitates the incorporation and interrogation of key elements of the local prostatic tumour microenvironment. Primary patient-derived cancer-associated fibroblasts (CAFs) were cultured in three-dimensional (3D) melt electrowritten scaffolds where they deposited extensive extracellular matrix (ECM) and promoted significant changes in prostate epithelial morphology, when compared to matched non-malignant prostatic fibroblasts (NPFs). The addition of mast cells, a resident prostatic immune population that is expanded during early malignancy, enhanced the morphometric transition of benign epithelia via a tryptase-mediated mechanism. Our patient-specific 3D microtissues reveal a cascade of interactions between prostatic CAFs, their native ECM and mast cell-derived tryptase, rendering them important microenvironmental drivers of prostate cancer progression

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

IntroductionHuman papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC.Methods and analysisWomen aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT01881659

Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.

AIM: Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data. METHODS: This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. RESULTS: This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients. CONCLUSIONS: In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease