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. Cancer Epidemiol Biomarkers Prev; 20(7); 1315-21. (C)2011 AACR.