Filomena Aste Silveira1, Gutemberg Almeida1, Yara Furtado2, Kátia S Silva3, Paula Maldonado4, Silvia Cavalcanti5, Maria da Gloria da Costa Carvalho6. 1. 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. 2. 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. 3. National Institute of Women, Children, and Adolescent Health, Fernandes Figueira Institute, Oswaldo Cruz Foundation (Fundação Osvaldo Cruz - FIOCRUZ), Brazil. 4. Institute of Gynecology, Federal University of Rio de Janeiro - UFRJ, Brazil. 5. Department of Microbiology and Parasitology of Fluminense Federal University (Universidade Federal Fluminense - UFF), Brazil. 6. Laboratory of Molecular Pathology, Department of Pathology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro - UFRJ, Brazil.
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. CONCLUSION: 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.
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. CONCLUSION: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.