Evaluation of p16INK4α Hypermethylation from Liquid-based Pap Test Samples in Vietnamese Population

BACKGROUND Human papillomavirus (HPV) infection has been considered as main cause of cervical cancer. Recently, aberrant DNA methylation at tumor suppressor genes (TSGs), leading to inactivation, has also been an early epigenetic event and cofactor in cervical carcinogenesis. This study was performed to evaluate an association between the hypermethylation of p16INK4α gene's promoter and HPV exposure in non-invasive samples (liquid-based papanicolaous samples) in Vietnamese population. METHODS 109 liquid-based papanicolaous test samples were archived and admitted from the Medic Medical Center and Au Lac Clinic Laboratory, Vietnam, from 2011-2014. Methylation-Specific-PCR (MSP) was performed to analyze methylation status from the liquid-based papanicolaous test samples identified whether HPV/or non-HPV, high-risk/low-risk HPV infection. RESULTS An upward trend was observed concerning the p16INK4α hypermethylation frequency in high-risk HPV infection, counting for 55.6%, and the low methylation frequency in low-risk and non-HPV infected samples, counting for 22.9%, 8.0%, respectively. The significant correlation between candidate p16INK4α hypermethylation and HPV exposure was observed (P<0.0001). Moreover, the odds ratio (OR) and relative risk (RR) were found in statistical significant value. (OR=5.76, 95%CI: 2.36 - 14.04, P<0.01; RR=3.11, 95%CI: 1.75-5.53, P<0.01). CONCLUSION Presence of p16INK4α hypermethylation was the specific characteristic of high-risk HPV infected samples in Vietnamese population. The OR and RR values showed that the strong correlation between p16INK4α hypermethylation and high-risk HPV infection, in which increased the risk of cervical cancer. The combination of p16INK4α hyper-methylation and HPV detection based biomarker could be used in non-invasive samples obtained from high-risk cancer patients, offer significant practical advantages.