Human papillomavirus type specific DNA and RNA persistence--implications for cervical disease progression and monitoring.

In 2000, we monitored the course and persistence of human papillomavirus (HPV) infection in 54 women who were HPV positive and free of any cytological disease using HPV-DNA genotyping with a linear array assay (baseline). The impact of HPV infection on development of cervical cytological abnormality (dyskaryosis) was monitored by repeat HPV genotyping and cytological assessment 2 years later. Detection of mRNA transcripts of known HPV oncogenes E6 and E7 using NASBA methodology and specific molecular beacons for five common HPV types was also performed at both time points. A total of 11/54 (20%) women developed dyskaryosis after 2 years with 31/54 and 23/54 women exhibiting transient and persistent infections respectively, as monitored by DNA genotyping. Women who maintained type-specific persistent HPV infection were significantly more likely to develop dyskaryosis compared to those who exhibited a transient infection (P = 0.001). The presence of HPV mRNA E6/E7 transcripts was less sensitive but more specific for the detection of disease at follow up. Moreover, women who were DNA positive and also positive for mRNA transcripts at baseline were significantly more likely to harbour persistent infection compared to those in whom DNA only was detected at baseline (P = 0.013). This study highlights the importance of detecting persistent type specific HPV infection to identify those women more at risk of developing cervical abnormalities, either by repeated DNA genotyping, or potentially by RNA based techniques that may be more predictive of persistent infection if performed at a single time point.