Evaluation of Human Papillomavirus Type Replacement Post-vaccination Must Account for Diagnostic Artifacts: Masking of HPV52 by HPV16 in Anogenital Specimens

摘要

It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine-targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent post-vaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in co-infected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously “masked” types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16+/study). Multivariate logistic regression, with adjustment for age and number of sexual partners was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n=1,196), presence of HPV16 was positively associated with HPV52 detection (adjusted OR=1.47, 95% CI 0.76-2.82). In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV infected males (HIPVIRG study; adjusted OR=3.82, 95% CI 1.19-12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend=0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed.