Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples
Por:
Escobar-Escamilla, Noe, González-Martínez B.E., Araiza-Rodriguez, Adnan, Fragoso-Fonseca D.E., Pedroza-Torres, Abraham, Landa-Flores M.G., Garces-Ayala, Fabiola, Mendieta-Condado, Edgar, Díaz-Quiñonez J.A., Castro-Escarpulli, Graciela, Ramírez-González J.E.
Publicada:
1 ene 2019
Resumen:
Human papillomavirus genotype 16 (HPV16) is the most frequent high-risk HPV (HR-HPV) identified in cervical precursor lesions and cervical cancer (CC) worldwide. The oncogenic potential of HPV16 is partly dependent on the lineage involved in the infection and the presence of clinically relevant mutations. In this report, we present the distribution of HR-HPV and the mutational profile and intra-host variability of HPV16 lineages, based on analysis of the long control region (LCR) and the E6 gene in samples with normal cytology (n = 39), squamous intraepithelial lesions (n = 25), and CC (n = 39). HR-HPV genotyping was performed using multiplex real-time PCR. HPV16 lineage assignments and mutation frequencies were determined by conventional PCR and Sanger DNA sequencing, and intra-patient viral populations were analyzed using next-generation sequencing (NGS). The most frequent HR-HPV type was HPV16, followed by HPV31 and HPV18. The frequency of HPV16 sublineages was A1/A2 > D2 > D3 and B1. Moreover, the most frequent mutations, both in samples from this study and in the available sequences from Mexican isolates in the GenBank database were LCR-G7518A, which is involved in carcinogenesis, and E6-T350G (producing L83V), associated with persistence of infection. Otherwise, deep sequencing revealed high conservation of viral lineages and mutations, independently of the stages studied. In conclusion, the high frequency and stability of these molecular markers, as well as the circulating viral lineages, could be related to the incidence of CC associated with HPV16. Hence, they deserve a broader analysis to determine the risk of specific populations for progression of the disease. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.
Filiaciones:
Escobar-Escamilla, Noe:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Laboratorio de Investigación Clínica y Ambiental, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), Mexico City, Mexico
Secretaria Salud Mexico, Inst Diagnost & Referencia Epidemiol InDRE Dr Man, Mexico City, DF, Mexico
Inst Politecn Nacl, Lab Invest Clin & Ambiental, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico
González-Martínez B.E.:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Araiza-Rodriguez, Adnan:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Secretaria Salud Mexico, Inst Diagnost & Referencia Epidemiol InDRE Dr Man, Mexico City, DF, Mexico
Fragoso-Fonseca D.E.:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Pedroza-Torres, Abraham:
Cátedra CONACyT, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología (INCan), Secretaría de Salud, Mexico City, Mexico
Secretaria Salud Mexico, Catedra CONACyT, Clin Canc Hereditario, Inst Nacl Cancerol INCan, Mexico City, DF, Mexico
Landa-Flores M.G.:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Garces-Ayala, Fabiola:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Secretaria Salud Mexico, Inst Diagnost & Referencia Epidemiol InDRE Dr Man, Mexico City, DF, Mexico
Mendieta-Condado, Edgar:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Secretaria Salud Mexico, Inst Diagnost & Referencia Epidemiol InDRE Dr Man, Mexico City, DF, Mexico
Díaz-Quiñonez J.A.:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
División de Estudios de Posgrado, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Castro-Escarpulli, Graciela:
Laboratorio de Investigación Clínica y Ambiental, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), Mexico City, Mexico
Inst Politecn Nacl, Lab Invest Clin & Ambiental, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico
Ramírez-González J.E.:
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) “Dr. Manuel Martínez Báez”, Secretaría de Salud, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Div Estudios Posgrad, Mexico City, DF, Mexico
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