Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women.

BACKGROUND Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role. METHODS HPV16-positive women with normal cytology in a large Danish cohort were reassessed for HPV16 status at 2 years and followed-up for cervical intraepithelial neoplasia 3 or worse (CIN3+) over 11 years through linkage with a national pathology database. Relative risks for clearance, persistence, and progression were compared with different HPV16 variant lineages based upon E6 gene sequencing. RESULTS Sixty-two (23.7%) of 261 HPV16 infections were persistent at 2 years, and 32 (51.6%) persistent infections progressed to CIN3+. The majority of baseline infections belonged to the European lineage (97.3%), with EUR-350T and EUR-350G accounting for 61.3% and 36.0% of infections, respectively. At two years, the proportion of HPV16 infections that persisted was significantly higher for EUR-350T (28.2%) than EUR-350G (15.9%) variants (odds ratio = 2.06, 95% CI, 1.04-4.25). This increased risk for persistence was consistent both in the absence (OR = 2.16, 95% CI, 0.84-6.26) or presence (OR = 1.89, 95% CI, 0.76-5.15) of progression to CIN3+. Among persistent HPV16 infections, there was no significant difference in risk of progression to CIN3+ between EUR-350T and EUR-350G sub-lineages, which were both associated with a substantial absolute risk (>50%) of CIN3+. CONCLUSIONS Significant differences in risk for persistence exist between the HPV16 variants that predominate in Europe. IMPACT Understanding the genetic basis of HPV16 persistence and carcinogenicity may help unravel important interactions between HPV16 and the host immune system.