Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16 INK4a and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16 INK4a and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5′ CpG island of the p16 INK4a and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16 INK4a and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16 INK4a gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.
Introduction: Many studies have indicated a causal relationship between genital human papillomavirus (HPV) infections and cervical cancer. This study aimed to determine the prevalence and genotypes of six high-risk oncogenic human papillomaviruses in cervical lesions from Moroccan women with normal and abnormal cytology. Methodology: The study included 938 women from the Children's and Mothers' Pathology Department of Ibn Sina Hospital, Rabat. Cytopathology examination was done by routine PAP smear testing. HPV DNA testing was conducted using DNA amplification by Polymerase Chain Reaction with subsequent typing by hybridization with specific probes for HPV types 16, 18, 31, 33, 35 and 45. Results: Cytopathology testing showed that only 16.3 % had an abnormal cytology, with a predominance of atypical squamous cell of undetermined significance (ASCUS) cases. The overall HPV prevalence was 15.7%. According to the cytology results, HPV infection was detected in 15.8% of normal and 14.38% of abnormal cases. Specific HPV genotyping showed a predominance of HPV 16 and 18. Double infection (HPV 16 + 18) was found in two cases whereas multiple infections (HPV 16+18+31) were detected in only one case. Evaluation of the relationship between HPV status and some environmental risk factors, including individual, socio-economic, and hygiene status, showed a significant association between HPV infection and oral contraceptive use. Conclusion: Based on these data, a combination of cytology and HPV DNA testing allows for identification of patients with a high risk of developing high-grade cervical lesions and improves cervical cancer prevention.
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