La relación profesor–alumno en la Maestría de Enfermedades Infecciosas y Zoonóticas

Revista Portal de la Ciencia, No. 7, diciembre 2014; 13-18Revista Portal de la Ciencia, No. 7, diciembre 2014; 13-1

Cáncer de laringe y Virus del papiloma humano en adultos del Hospital Escuela Universitario, Honduras

Introduction: laryngeal cancer is the most frequent in head and neck, recently HPV is involved in its carcinogenesis. Objective: To identify the presence of human papillomavirus (HPV) in patients with larynx carcinoma at HEU from March 2012 until March 2015.Methods: A retrospective study was performed. Under authorization of the Pathology Department, the histopathological studies from patients already diagnosed having laryngeal carcinoma during the period from March 2012- March 2015 were reviewed. A universe of 91 patients with larynx carcinoma was obtained. In the selected 30 patients whose specimens were preserved in paraffin blocks, HPV DNA identification by polymerase chain reaction (PCR) followed by molecular genotyping using hybridization probes by reverse LIPA (INMO - LIPA HPV Genotyping Extra) were accomplished.Results: Gender distribution: 26/30 (86.6 %) men and 4/30 (13.3 %) women with a mean age of 62.7 yearsin HVP positive patients was 54.8 years .Coming largely from the rural areas19/30(63.3 %). The risk co-factors identified weresmoking22/30(73.3 %) and alcoholism 20/30(66.6 %).The most affected anatomic site: the glottis 16/30 (53.3 %). Histologically prevailed in 21/30 (70 %) of patients moderately differentiated squamous cell carcinoma. Most patients were in stage III12/30(40 %) at the diagnosis time, (p=0.09).HPV prevalence was 13/30(43.3%), IC95% (25.5-62.6), p<0.001. High risk genotypes (16, 31, 33, 51, 52, 53, 56, 58), as well as low risk (6, 11, 71 and 74) were identified. Non-oncogenic HPV 11 (23%) was the most frequent type encountered and the oncogenic HPV 16 (15.4%). Co-infection was noted with two or more genotypes.Conclusions: Prevalence HPV was 43.3%. HPV 11 and 16 were the most frequent. Due to a reduce sample and results variability among international studies, it is not possible to establish a clear association between HPV and laryngeal cancer. Further studies with more representative sample are required and recommended.Revista Portal de la Ciencia, No.11, diciembre 2016, 40-53El cáncer de laringe es el más frecuente en cabeza y cuello; recientemente se plantea la infección por virus del papiloma humano (VPH) en la carcinogénesis. El objetivo del estudio fue establecer la presencia del VPH en pacientes con carcinoma de laringe en el Hospital Escuela Universitario (HEU) desde marzo de 2012 a marzo de 2015.Se hizo un estudio retrospectivo. Previa autorización del Departamento de Patología se revisaron los diagnósticos histopatológicos de pacientes con carcinoma de laringe en HEU. El universo fue de 91 pacientes con carcinoma de laringe; la muestra fue de 30 pacientes.Se identificó el ADN del VPH mediante la reacción en cadena de la polimerasa (PCR) y genotipificación molecular utilizando sondas marcadas mediante hibridación reversa LIPA (INNO-LIPA HPV Genotyping Extra). Se realizó tabulación y análisis en EPIINFO 3.5.4; se obtuvo frecuencias, porcentajes, medidas de tendencia central y de significancia estadística.Los resultados indican distribución por género, masculino 26/30 (86.6 %) y femenino 4/30 (13.3 %); edad media para VPH negativos (62.7 años) y para VPH positivos (54.8 años). Procedentes del área rural 19/30(63.3 %). Cofactores predominantes: el tabaquismo en 22/30 (73.3 %) y alcoholismo 20/30 (66.6 %). El sitio anatómico más afectado fue la glotis 16/30(53.3 %). Histológicamente predominó el carcinoma epidermoide moderadamente diferenciado 21/30 (70 %). Al momento del diagnóstico12/ 30(40 %) se encontraban en estadio III.El porcentaje de VPH fue del 43.3 % (13/30), IC 95%(25.5-62.6), p< 0.001. Se identificaron genotipos de alto riesgo (16, 31, 33, 51, 52, 53, 56, 58) y bajo riesgo (6, 11, 71 y 74), predominando VPH 11 (23 %) no oncogénico, seguido del VPH 16 (15.4 %) oncogénico. Hubo coinfección de dos o más genotipos.La conclusión es que el porcentaje de VPH fue del 43.3 % con predominio de VPH 11 y 16. Debido a la muestra reducida y a la variabilidad de los resultados en estudios internacionales, se recomiendan estudios futuros con casuística más grande.Revista Portal de la Ciencia, No.11, diciembre 2016, p.40-5

Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study

Q1Q1Pacientes con Virus del Papiloma Humano (VPH)VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study-trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty-two HPV-positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2-89.5) among women <50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9-86.6). Overall specificity was 58.6% (95% CI 56.7-60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8-73.5) compared to women <50 (54.3%, 95% CI 52.1-56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9-38.6) compared to women <50 (53.2, 95% CI 51.1-55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%-95.4%, 44.9%-94.4%, 8.2%-65.3%, 0%-98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV-positive women performed by trained providers was high with an important reduction in referral rates. However, scaling-up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.https://orcid.org/0000-0001-7187-9946Revista Internacional - IndexadaA1N

Identification of Human Papillomavirus Type 58 Lineages and the Distribution Worldwide

Background. Human papillomavirus type 58 (HPV-58) accounts for a much higher proportion of cervical cancers in East Asia than other types. A classification system of HPV-58, which is essential for molecular epidemiological study, is lacking. Methods and results. This study analyzed the sequences of 401 isolates collected from 15 countries and cities. The 268 unique concatenated E6-E7-E2-E5-L1-LCR sequences that comprised 57% of the whole HPV-58 genome showed 4 distinct clusters. L1 and LCR produced tree topologies that best resembled the concatenated sequences and thus are the most appropriate surrogate regions for lineage classification. Moreover, short fragments from L1 (nucleotides 6014–6539) and LCR (nucleotides 7257–7429 and 7540–52) were found to contain sequence signatures informative for lineage identification. Lineage A was the most prevalent lineage across all regions. Lineage C was more frequent in Africa than elsewhere, whereas lineage D was more prevalent in Africa than in Asia. Among lineage A variants, sublineage A2 dominated in Africa, the Americas, and Europe, but not in Asia. Sublineage A1, which represents the prototype that originated from a patient with cancer, was rare worldwide except in Asia. Conclusions. HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study

Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America : an analysis within the ESTAMPA study

Corresponding author. E-mail address: [email protected] (A.T. Ramírez).Background. Cervical cytology remains widely used as the initial tool in cervical cancer screening worldwide. WHO guidelines recommend replacing cytology with primary HPV testing to reach cervical cancer elimination goals. We assessed the performance of cytology and high-risk HPV testing to detect cervical precancer, cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) among women aged 30–64 years participating in the ESTAMPA study. Methods. Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy collection and treatment as needed. Those with no evident precancer were recalled at 18-months for a second HPV test to complete disease ascertainment. Performance indicators for cytology and HPV to detect CIN3+ were estimated. Findings. 30,606 participants with available cytology and HPV results were included in the analysis. A total of 440 histologically confirmed CIN3s and 30 cancers were diagnosed. Cytology sensitivity for CIN3+ was 48.5% (95% CI: 44.0–53.0), whereas HPV testing had a sensitivity of 98.1% (95% CI: 96.3–96.7). Specificity was 96.5% (95% CI: 96.3–96.7) using cytology and 88.7% (95% CI: 88.3–89.0) with HPV. Performance estimates varied substantially by study centre for cytology (ranging from 32.1% to 87.5% for sensitivity and from 89.2% to 99.5% for specificity) while for HPV results were more consistent across sites (96.7%–100% and 83.6–90.8%, respectively). Interpretation. The limited and highly variable sensitivity of cytology strongly supports transition to the more robust and reproducible HPV-based cervical screening to ensure progress towards global cervical cancer elimination targets in Latin America.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Proyectos de investigación y desarroll

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus : results from the ESTAMPA multicentric screening study

Correspondence to: Dr Joan Valls, Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon 69366, France. [email protected]. Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. Methods. This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30–64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Findings. Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7–49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9–93·2) for CIN3+, whereas specificity was 50·1% (48·5–51·8) for less than CIN2 and 47·1% (45·5–48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3–95·3] in those aged 30–49 years vs 77·6% [68·6–85·0] in those aged 50–65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8–47·6] vs 61·8% [58·7–64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). Interpretation. Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Proyectos de investigación y desarrollo14-INV-036PINV18-25

Implementing HPV testing in 9 Latin American countries : the laboratory perspective as observed in the ESTAMPA study

Correspondence: Maribel Almonte [email protected] article was submitted to Infectious Diseases - Surveillance, Prevention and Treatment, a section of the journal Frontiers in Medicine.Background: Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings. Methods: We describe the implementation process of HPV testing in ESTAMPA, focusing on laboratory aspects. We assess the readiness of 12 laboratories to start HPV testing and their continuity capacity to maintain good quality HPV testing until end of recruitment or up to December 2021. Readiness was based on a checklist. Information from the study database; regular meetings and monitoring visits; and a questionnaire on laboratory operational aspects sent in May 2020 were used to assess continuity capacity. Compliance with seven basic requirements (readiness) and eight continuity requirements (continuity capacity) was scored (1 = compliant, 0 = not compliant) and totaled to classify readiness and continuity capacity as very limited, limited, moderate or high. Experiences, challenges, and enablers of the implementation process are also described. Results: Seven of 12 laboratories had high readiness, three moderate readiness, and of two laboratories new to HPV testing, one had limited readiness and the other very limited readiness. Two of seven laboratories with high readiness also showed high continuity capacity, one moderate continuity capacity, and the other four showed limited continuity capacity since they could not maintain good quality HPV testing over time. Among three laboratories with moderate readiness, one kept moderate continuity capacity and two reached high continuity capacity. The two laboratories new to HPV testing achieved high continuity capacity. Based on gained expertise, five laboratories have become part of national screening programs. Conclusion: High readiness of laboratories is an essential part of effective implementation of HPV testing. However, high readiness is insufficient to guarantee HPV testing high continuity capacity, for which a "culture of quality" should be established with regular training, robust monitoring and quality assurance systems tailored to local context. All efforts to strengthen HPV laboratories are valuable and crucial to guarantee effective implementation of HPV-based cervical screening.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Proyectos de investigación y desarroll

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

Rotavirus Genotypes in Costa Rica, Nicaragua, Honduras and the Dominican Republic

In this study, 574 stool samples from children with gastroen- teritis were obtained from different hospitals in Costa Rica, Honduras, Nicaragua and the Dominican Republic during 2005–2006. Diarrhea stool samples were analyzed for rotavi- rus by ELISA and typed by the RT-PCR-based method. Un- usual strains were detected: G1P6, G2P8, G3P6, G9P4 and mixed infections. Recent studies have indicated that unusu- al human rotavirus strains are emerging as global strains, which has important implications for effective vaccine de- velopment. In this context, the next generation of rotavirus vaccines will need to provide adequate protection against diseases caused not only by mixed infections, but also by unusual G/P combinations.En este estudio, 574 muestras de heces de niños con gastroen- teritis se obtuvieron de diferentes hospitales de Costa Rica Honduras, Nicaragua y la República Dominicana durante 2005-2006. Las muestras de heces con diarrea se analizaron para detectar rotavi- rus por ELISA y se tipificaron por el método basado en RT-PCR. No se detectaron las cepas habituales: Se detectaron cepas no habituales: G1P6, G2P8, G3P6, G9P4 y infecciones mixtas. Estudios recientes han indicado que las cepas inusuales de rotavirus humano de los rotavirus humanos están emergiendo como cepas globales, lo que tiene importantes implicaciones para el desarrollo de vacunas eficaces. de vacunas. En este contexto, la próxima generación de vacunas contra el rotavirus de vacunas contra el rotavirus tendrá que ofrecer una protección adecuada contra contra las enfermedades causadas no sólo por infecciones mixtas, sino también por combinaciones inusuales de G/P.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari