Principal Investigator

Maribel
Almonte
Awardee Organization

International Agency For Res On Cancer
United States

Fiscal Year
2021
Activity Code
UH3
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Development and clinical validation of a multi-type HPV E6/E7 oncoprotein test for cervical cancer screening and triage in low- and middle-income countries

Cervical cancer remains a leading cause of cancer incidence and mortality in most low and middle income countries (LMIC). Despite cytology based screening programs have reduce cervical cancer mortality up to 80% in developed nations, these programs have frequently failed success in developing countries mainly due to the requirement of multiple visits to identify women at risk who require treatment. The low sensitivity of cervical cytology (around 50%) induces the frequent repetition of the test through lifetime screening; in addition, the complementary diagnosis with colposcopy-biopsy requires women to attend multiple visits in the short time to undergo proper treatment. Recently, highly sensitive and reproducible laboratory techniques to detect carcinogenic HPV have been developed and approved by FDA as primary cervical cancer screening tests. Randomized clinical trials have demonstrated that HPV testing is more sensitive than cytology to detect cervical cancer precursors (around 90% vs 50%) and it has also been shown that HPV testing detects more disease at an earlier stage and induces a greater reduction in cervical cancer mortality. These technologies are changing screening practices in low and middle income countries such as Mexico, Argentina, Colombia, and El Salvador. Despite its advantages, HPV tests have a low positive predictive value; thus, they require additional diagnostic procedures (triage) to avoid overburden of colposcopy clinics or overtreatment if no confirmatory diagnosis is performed (see-and-treat programs). Currently, the triage for positive women is done with cytology, which again, due to the low sensitivity produces a high recall rate challenging screening programs in low resource settings. At the moment none of the triage tests under investigation is suitable for screening programs in LMIC due to the induction of high recall rates or high logistic or infrastructure requirements for its implementation. The development of a highly accurate test in a friendly/manual format producing results on individual basis will help improve outcomes of screening programs in low resource settings. We will use the platform of a cervical cancer research network already in place in Latin American countries (LAC) to: (Aim 1) developed and improved HPV test based on E6/E7 oncoprotein activity for the 8 most common HPV types associated with cervical cancer; (Aim 2) assess the potential clinical performance of the 8-HPV type E6/E7-based OncoProtein Cervical Test by challenging it against the whole spectrum of disease's histological diagnosis in 800 samples; (Aim 3) asses the sensitivity and specificity of the test for the detection of cancer precursors among HPV positive women (triage) in 4,500 women from the ESTAMPA study; (Aim 4) assess the potential of the test as standalone test for cervical cancer screening by using a sample of additional 1,000 HPV negative women; (Aim 5) to compare the results (positive/negative) of the 8-HPV type E6/E7-based OncoProtein Cervical Test with HPV persistence and development of cervical lesions after 18 months of women follow-up; (Aim 6) identify differences in the performance of test in different settings by processing 4,500 samples in three different labs in LAC; (Aim 7) identify operational requirements for scaling up cervical cancer screening programs based on the 8-HPV type E6/E7-based OncoProtein Cervical Test by performing 1,500 samples in real time in five different LAC; (Aim 8) describe differences in sensitivity and specificity between the origina OncoE6TM Cervical Test that included oncoproteins for HPV 16 and 18 and the new 8-HPV type E6/E7-based OncoProtein Cervical Test.

Publications

  • Correa RM, Baena A, Valls J, Colucci MC, Mendoza L, Rol M, Wiesner C, Ferrera A, Fellner MD, González JV, Basiletti JA, Mongelos P, Rodriguez de la Peña M, Saino A, Kasamatsu E, Velarde C, Macavilca N, Martinez S, Venegas G, Calderón A, Rodriguez G, Barrios H, Herrero R, Almonte M, Picconi MA, ESTAMPA Study Group. Distribution of human papillomavirus genotypes by severity of cervical lesions in HPV screened positive women from the ESTAMPA study in Latin America. PloS one. 2022 Jul 29;17(7):e0272205. doi: 10.1371/journal.pone.0272205. eCollection 2022. PMID: 35905130
  • Ferrera A, Valladares W, Cabrera Y, de la Luz Hernandez M, Darragh T, Baena A, Almonte M, Herrero R. Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer. International journal of cancer. 2019 Oct 15;145(8):2042-2050. Epub 2019 Feb 19. PMID: 30684396
  • Basiletti JA, Valls J, Poklépovich T, Fellner MD, Rol M, Alonso R, Correa RM, Colucci MC, Rodríguez de la Peña M, Falabella PG, Saíno A, Campos J, Herrero R, Almonte M, Picconi MA. Human papillomavirus genotyping using next generation sequencing (NGS) in cervical lesions: Genotypes by histologic grade and their relative proportion in multiple infections. PloS one. 2022 Nov 23;17(11):e0278117. doi: 10.1371/journal.pone.0278117. eCollection 2022. PMID: 36417453
  • Rol ML, Picconi MA, Ferrera A, Sánchez GI, Hernández ML, Lineros J, Peraza A, Brizuela M, Mendoza L, Mongelós P, Cabrera Y, Rodríguez de la Peña M, Correa RM, Terán C, Colque Reynaga D, García L, Ramírez AT, Hernández-Nevarez P, Doimi F, Ramón M, Arias-Stella J, Zúñiga M, Villagra V, Bobadilla ML, Cardinal L, Valls J, Lucas E, Baena A, Fleider L, Venegas G, Cruz-Valdez A, Rodríguez G, Calderón A, Wiesner C, Luciani S, Broutet N, Herrero R, Almonte M. Implementing HPV testing in 9 Latin American countries: The laboratory perspective as observed in the ESTAMPA study. Frontiers in medicine. 2022 Nov 17;9:1006038. doi: 10.3389/fmed.2022.1006038. eCollection 2022. PMID: 36465901
  • Ramírez AT, Valls J, Baena A, Rojas FD, Ramírez K, Álvarez R, Cristaldo C, Henríquez O, Moreno A, Reynaga DC, Palma HG, Robinson I, Hernández DC, Bardales R, Cardinal L, Salgado Y, Martínez S, González E, Guillén D, Fleider L, Tatti S, Villagra V, Venegas G, Cruz-Valdez A, Valencia M, Rodríguez G, Terán C, Picconi MA, Ferrera A, Kasamatsu E, Mendoza L, Calderon A, Luciani S, Broutet N, Darragh T, Almonte M, Herrero R, ESTAMPA Study Group, Rol ML, Lucas E, Hernández ML, Sánchez GI, Murillo R, Jerónimo J, Ferreccio C, Rodríguez MI, Cabrera Y, Salgado B, Colucci MC, Saino MA, Rodríguez de la Peña M, Fernández DL, García L, Caserta B, Doimi F, Lazcano-Ponce E. Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study. Lancet regional health. Americas. 2023 Sep 20;26:100593. doi: 10.1016/j.lana.2023.100593. eCollection 2023 Oct. PMID: 37766799
  • Kasamatsu E, Rodríguez Riveros MI, Soilan AM, Ortega M, Mongelós P, Páez M, Castro A, Cristaldo C, Báez FR, Centurión CC, Vester J, Barrios H, Villalba G, Amarilla ML, Giménez G, Caubere E, Hernández ML, Baena A, Almonte M, Herrero R, Mendoza LP, ESTAMPA Paraguay Center study group. Factors associated with high-risk human papillomavirus infection and high-grade cervical neoplasia: A population-based study in Paraguay. PloS one. 2019 Jun 27;14(6):e0218016. doi: 10.1371/journal.pone.0218016. eCollection 2019. PMID: 31246959
  • Baena A, Mesher D, Salgado Y, Martínez S, Villalba GR, Amarilla ML, Salgado B, Flores B, Bellido-Fuentes Y, Álvarez-Larraondo M, Valls J, Lora O, Virreira-Prout G, Figueroa J, Turcios E, Soilán AM, Ortega M, Celis M, González M, Venegas G, Terán C, Ferrera A, Mendoza L, Kasamatsu E, Murillo R, Wiesner C, Broutet N, Luciani S, Herrero R, Almonte M, ESTAMPA study group. Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study. International journal of cancer. 2023 Apr 15;152(8):1581-1592. Epub 2022 Dec 7. PMID: 36451311
  • Arrossi S, Almonte M, Herrero R, Gago J, Sánchez Antelo V, Szwarc L, Thouyaret L, Paolino M, Wiesner C. Psycho-social impact of positive human papillomavirus testing in Jujuy, Argentina results from the Psycho-Estampa study. Preventive medicine reports. 2020 Mar 5;18:101070. doi: 10.1016/j.pmedr.2020.101070. eCollection 2020 Jun. PMID: 32257775
  • Valls J, Baena A, Venegas G, Celis M, González M, Sosa C, Santin JL, Ortega M, Soilán A, Turcios E, Figueroa J, Rodríguez de la Peña M, Figueredo A, Beracochea AV, Pérez N, Martínez-Better J, Lora O, Jiménez JY, Giménez D, Fleider L, Salgado Y, Martínez S, Bellido-Fuentes Y, Flores B, Tatti S, Villagra V, Cruz-Valdez A, Terán C, Sánchez GI, Rodríguez G, Picconi MA, Ferrera A, Mendoza L, Calderón A, Murillo R, Wiesner C, Broutet N, Luciani S, Pérez C, Darragh TM, Jerónimo J, Herrero R, Almonte M, ESTAMPA study group. 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. The Lancet. Global health. 2023 Mar;11(3):e350-e360. PMID: 36796982
  • Almonte M, Murillo R, Sánchez GI, González P, Ferrera A, Picconi MA, Wiesner C, Cruz-Valdez A, Lazcano-Ponce E, Jerónimo J, Ferreccio C, Kasamatsu E, Mendoza L, Rodríguez G, Calderón A, Venegas G, Villagra V, Tatti S, Fleider L, Terán C, Baena A, Hernández ML, Rol ML, Lucas E, Barbier S, Ramírez AT, Arrossi S, Rodríguez MI, González E, Celis M, Martínez S, Salgado Y, Ortega M, Beracochea AV, Pérez N, Rodríguez de la Peña M, Ramón M, Hernández-Nevarez P, Arboleda-Naranjo M, Cabrera Y, Salgado B, García L, Retana MA, Colucci MC, Arias-Stella J, Bellido-Fuentes Y, Bobadilla ML, Olmedo G, Brito-García I, Méndez-Herrera A, Cardinal L, Flores B, Peñaranda J, Martínez-Better J, Soilán A, Figueroa J, Caserta B, Sosa C, Moreno A, Mural J, Doimi F, Giménez D, Rodríguez H, Lora O, Luciani S, Broutet N, Darragh T, Herrero R. Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol. BMJ open. 2020 May 24;10(5):e035796. PMID: 32448795