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1.
Int J Cancer ; 155(5): 816-827, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602045

RESUMO

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.


Assuntos
Detecção Precoce de Câncer , Infecções por HIV , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/complicações , Detecção Precoce de Câncer/métodos , Infecções por HIV/virologia , Infecções por HIV/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Adulto , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Países em Desenvolvimento , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , América Latina/epidemiologia , DNA Viral/análise , DNA Viral/genética , África/epidemiologia
2.
Intervirology ; 67(1): 83-98, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38981462

RESUMO

INTRODUCTION: Diarrheal diseases constitute a significant public health problem in terms of mortality and morbidity. In Honduras and around the world, RVs have consistently emerged as the single most important etiologic agent in acute childhood diarrhea. However, other viruses, such as NoVs and HAstVs, have also been shown to be responsible for viral gastroenteritis. Unfortunately, the country has limited information concerning the etiologic role of these viral agents in acute gastroenteritis. This study investigated the frequency, genotypes, and epidemiological characteristics of RV-A, NoVs, and HAstVs among children under 5 years old in Distrito Central, Honduras. METHODS: Stool samples and their corresponding epidemiological data were collected from children with acute gastroenteritis in three healthcare centers in Distrito Central. All samples were screened by immunoassays for RV-A and HAstVs. RV-A-positive samples were molecularly characterized by RT-PCR and genotyping assays. RT-PCR was also applied to confirm HAstVs positivity and to detect NoVs, followed by nucleotide sequencing to assign their genotypes. RESULTS: Our results show that at least one viral agent was detected in 31% of the children. The frequency of RV-A, NoVs, and HAstVs was 14%, 13%, and 5%, respectively. The most frequent RV-A genotype was G2P[4], occurring in 93% of cases. 92.3% of NoVs-positive samples belonged to genogroup II, with GII.4 and GII.16 being the most common. HAstVs were clustered into three genotypes: HAstV-1, HAstV-2, and HAstV-8. Only one sample showed coinfection with NoVs and HAstVs. CONCLUSION: This comprehensive molecular and epidemiological characterization of enteric viruses demonstrates the vast diversity of these agents and describes for the first time NoVs and HAstVs as causative agents of acute childhood gastroenteritis in Distrito Central, Honduras. This suggests that further in-depth studies of the pediatric population are necessary to develop and implement effective preventive and control measures in the country.


Assuntos
Fezes , Gastroenterite , Genótipo , Humanos , Honduras/epidemiologia , Gastroenterite/virologia , Gastroenterite/epidemiologia , Pré-Escolar , Lactente , Fezes/virologia , Masculino , Feminino , Diarreia/virologia , Diarreia/epidemiologia , Filogenia , Rotavirus/genética , Rotavirus/isolamento & purificação , Rotavirus/classificação , RNA Viral/genética , Norovirus/genética , Norovirus/classificação , Norovirus/isolamento & purificação , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Doença Aguda/epidemiologia , Recém-Nascido , Infecções por Enterovirus/virologia , Infecções por Enterovirus/epidemiologia
3.
Int J Cancer ; 145(8): 2042-2050, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30684396

RESUMO

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.


Assuntos
Proteínas de Ligação a DNA/genética , Detecção Precoce de Câncer/métodos , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/diagnóstico , Proteínas Repressoras/genética , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , DNA Viral/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/virologia , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologia
4.
Front Med (Lausanne) ; 9: 1006038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465901

RESUMO

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.

5.
BMJ Open ; 10(5): e035796, 2020 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448795

RESUMO

INTRODUCTION: 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: NCT01881659.


Assuntos
Alphapapillomavirus/isolamento & purificação , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Triagem , Displasia do Colo do Útero/diagnóstico , Adulto , Colposcopia , Feminino , Humanos , América Latina , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico
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