title: An upward trend in DNA p16ink4a methylation pattern and high risk HPV infection according to the severity of the cervical lesion.
abstract: High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.
authors.affiliation: Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, NiteróiRio de Janeiro, Brasil.
authors.forename: Fernanda Nahoum
authors.initials: FN
authors.lastname: Carestiato
authors.forename: Larissa Alves
authors.initials: LA
authors.lastname: Afonso
authors.forename: Natalia
authors.initials: N
authors.lastname: Moysés
authors.forename: Gutemberg Leão
authors.initials: GL
authors.lastname: Almeida Filho
authors.forename: Luis Guillermo Coca
authors.initials: LG
authors.lastname: Velarde
authors.forename: Silvia Maria Baeta
authors.initials: SM
authors.lastname: Cavalcanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics; D012720:Severity of Illness Index; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
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