Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women

Abstract

Background: This study aims at determining the correlation between CpG methylation in human papillomavirus (HPV)-16 L1 and the persistent infections and development of cervical carcinoma in Uyghur women. Methods: Among the 4,364 Uyghur women, specimens were collected from 145 (3.3%) HPV-16 single infected cases, which were divided into 5 groups: transient infection (n = 32), persistent infection (n = 21, 12 months), cervical intraepithelial neoplasia (CIN) grade 1 (CIN1, n = 21), CIN2-3 (n = 33) and invasive cervical cancer (n = 38) groups. Methylation level in HPV-16 L1 was quantified by pyrosequencing, and values in the prediction and diagnosis of CIN2+ lesions were evaluated with receiver operating characteristic curves. Results: With the progression of the disease, increased methylation was detected at 13 CpG sites, and a high methylation level was associated with the risk of CIN2+. The strongest related site was 6650 (OR 9.89, 95% CI 3.57-27.44). The area under ROC curve (AUC) of methylation at each CpG site to differentiate between CIN2+ and <CIN2 ranged from 0.756 to 0.862, and the greatest AUC was at position 6650 (AUC 0.862, 95% CI 0.803-0.920). A high methylation level at CpG site 6389, 6457, 6581, 6650, 6796 and 7034 was connected with increased risk of HPV-persistent infection, and the strongest associated CpG site was 6389 (OR 13.33, 95% CI 3.95-28.08). The AUC in the prediction of HPV persistent infection was in the range of 0.656-0.943 and the site with the highest diagnostic value was 6389 (AUC 0.943, 95% CI 0.884-1.000). Conclusions: These results indicate that the methylation of CpG sites in HPV-16 L1 has a great value in contributing to the prediction of HPV-persistent infection and cervical precancerous progression.