A new study led by researchers at the Democritus University of Thrace in Greece recently revealed a new potential biomarker for cervical cancer screening. The study was published in the journal Cancer Epidemiology and is entitled “PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis”.
Cervical cancer is the third most common diagnosed cancer in women. It is characterized by an abnormal cell growth in the cervix, the lower part of the uterus. Cervical cancer can be successfully treated when detected at an early stage, usually through a Papanicolaou (Pap) smear test, where the doctor scrapes a small sample of cervical cells to look for abnormal cell changes. The majority of cervical cancer cases are caused by the human papillomavirus (HPV), which can be transmitted by sexual contact. It is estimated that in 2015, 12,900 new cases of cervical cancer will be diagnosed in the United States resulting in 4,100 deaths.
Epigenetics refers to external modifications to DNA that do not change the DNA sequence but can control gene expression, the “on” and “off” status of genes. Aberrant epigenetic modifications can lead to several diseases including cancer. DNA methylation is one key mechanism of epigenetic regulation, where a methyl group is added to the cytosine (C) or adenine (A) nucleotides in the DNA molecule.
Methylation of paired boxed gene 1 (PAX1) has been suggested to be involved with cervical cancer pathophysiology. In the study, researchers investigated in a meta-analysis the use of PAX1 methylation as a potential biomarker of cervical cancer. In total, the studies considered on the analysis comprised 1,385 individuals with several cervical intraepithelial neoplasia (CIN) stages and normal cervical pathology. CIN is considered the potentially pre-malignant form of cervical cancer; the higher the grade, the higher the dysplasia (abnormal cell growth) degree. The diagnostic value of PAX1 methylation was assessed regarding CIN grade 2 or worse (CIN2+), and CIN grade 3 or worse (CIN3+) compared to normal controls.
Researchers reported that in terms of specificity, the assessment of PAX1 methylation was found to have a very good specificity for both CIN grades analyzed (0.92); in terms of overall sensitivity it was found to be 0.66 for CIN2+ and 0.77 to CIN3+. In general, a very good efficiency of the diagnostic test was found in both CIN grades.
The research team concluded that PAX1 methylation can be considered an auxiliary biomarker for cervical cancer screening. The authors suggest that this diagnostic assay could be potentially incorporated in the already existing screening protocols, as it might help detect cases of more advanced cervical abnormalities, helping to distinguish between benign anomalies and those requiring more intensive treatment, subsequently reducing the number of unnecessary interventions. However, the team advises that at this point, the cost efficiency of using PAX1 methylation as a potential diagnostic method should be carefully evaluated, and the protocols to be used properly developed and validated.