title: HPV DNA genotyping and methylation of gene p16 INK4A in cervical LSIL.
abstract: BACKGROUND
  DNA methylation is the most important epigenetic change involved in the control of gene expression in human cells. Methylation of the p16(INK4a) gene occurs early in the development of cervical cancer. Low-grade squamous intraepithelial lesions (LSILs) are prevalent, and their behavior is variable.
  
  
  OBJECTIVE
  To identify the HPV DNA type, detect the methylation status of the p16(INK4A) gene, and analyze their association with the cytological evolution of LSIL over a period of two years.
  
  
  METHODS
  We conducted a cohort study with 40 participants. Cervical scrapings were collected for cytological and molecular analysis. HPV DNA detection and typing were performed by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Methylation-specific PCR was performed to detect methylation.
  
  
  RESULTS
  HPV DNA was detected in 87% of the cases, and type 16 was the most frequent type. Methylation was detected in 11% of the cases and did not exhibit a significant correlation with the HPV type. Unfavorable cytological evolution exhibited a significant association with the presence of methylation.
  
  
  CONCLUSIONS
  HPV 16 was the most frequently detected type of HPV in LSIL. Methylation of the p16(INK4A) gene was infrequent and occurred independent of the presence of HPV DNA. Methylation of the p16(INK4a) gene exhibited a significant correlation with persistence/progression of LSIL.
authors.affiliation: Graduate Program in Surgical Science, Federal University of Rio de Janeiro (Universidade Federal do Rio de Janeiro - UFRJ), Brazil; Institute of Gynecology, Federal University of Rio de Janeiro - UFRJ, Brazil.
authors.forename: Filomena Aste
authors.initials: FA
authors.lastname: Silveira
authors.affiliation: Graduate Program in Surgical Science, Federal University of Rio de Janeiro (Universidade Federal do Rio de Janeiro - UFRJ), Brazil; Institute of Gynecology, Federal University of Rio de Janeiro - UFRJ, Brazil.
authors.forename: Gutemberg
authors.initials: G
authors.lastname: Almeida
authors.affiliation: Graduate Program in Surgical Science, Federal University of Rio de Janeiro (Universidade Federal do Rio de Janeiro - UFRJ), Brazil; Institute of Gynecology, Federal University of Rio de Janeiro - UFRJ, Brazil; Federal University of the State of Rio de Janeiro (Universidade Federal do Estado do Rio de Janeiro - UNIRIO), Brazil.
authors.forename: Yara
authors.initials: Y
authors.lastname: Furtado
authors.affiliation: National Institute of Women, Children, and Adolescent Health, Fernandes Figueira Institute, Oswaldo Cruz Foundation (Fundação Osvaldo Cruz - FIOCRUZ), Brazil.
authors.forename: Kátia S
authors.initials: KS
authors.lastname: Silva
authors.affiliation: Institute of Gynecology, Federal University of Rio de Janeiro - UFRJ, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Maldonado
authors.affiliation: Department of Microbiology and Parasitology of Fluminense Federal University (Universidade Federal Fluminense - UFF), Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cavalcanti
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro - UFRJ, Brazil.
authors.forename: Maria da Gloria da Costa
authors.initials: Mda G
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: Cervical intraepithelial neoplasia; Gene p16; Infection by papillomavirus; Methylation; PCR