Variant-specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high-risk (HR) variants] compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9-1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.