HPV infection and p16 promoter methylation as predictors of ASC-US/LSIL progression

Although patients found to have atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSILs) on Papanicolaou (Pap) testing are treated conservatively, 5.2% to 18.8% of them progress to high-grade squamous intraepithelial lesions (HSILs). The objective of the current study was to identify predictors of progression to HSIL and determine what percentage of ASC-US/LSIL cases harbor cervical intraepithelial neoplasia of grade 2 or higher.

The current study included 381 consecutive cases with ASC-US/LSIL. After the exclusion of 87 cases because of a history of dysplasia or loss to follow-up, 165 cases with follow-up cytology were used to analyze predictive factors of progression to HSIL, and 129 cases that underwent immediate tissue biopsy were subjected to correlation analysis between cytology and histology. Disease regression was defined as a reversion to normal or benign cellular changes, disease persistence as maintenance at ASC-US/LSIL, and disease progression as progression to HSIL. Data regarding clinical parameters were obtained from medical records. Methylation-specific polymerase chain reaction was performed using cytology samples to evaluate methylation of the p16 promoter.

Of 165 cases, 131 (79.4%) regressed, 23 (13.9%) were persistent, and 11 cases (6.7%) progressed. Human papillomavirus infection was more common in women with disease progression than in those with disease regression or persistence (P = .033). Promoter methylation of p16 in the cytology sample was more common in cases that progressed (5 of 6 cases) than in cases that regressed (0 of 8 cases). Twenty-three of 129 cases (17.8%) were found to harbor cervical intraepithelial neoplasia of grade 2 or higher on immediate tissue biopsy.

Human papillomavirus infection and p16 promoter methylation might be valuable surrogate markers of disease progression from ASC-US/LSIL to HSIL.