AbstractsBiology & Animal Science

Introduction: Infection with certain genotypes of human papillomavirus (HPV) is necessary in the development of cervical cancer. This discovery has led to the establishment of two vaccines that prevent the HPV genotypes that cause the majority (~70%) of cervical cancer cases (HPVs 16 and 18). However, other oncogenic HPV genotypes exist, which could increase in prevalence following reductions in HPV vaccine target genotypes 6, 11, 16 and 18, post-vaccination (i.e., "type replacement"), if certain conditions apply. For instance, if natural type competition exists between these vaccine and other genotypes, then type replacement may be more likely. The main objectives of this project were to evaluate HPV genotype competition and the potential for diagnostic artifacts, which could inhibit our ability to accurately compare pre- and post-vaccination HPV prevalence in vaccinated populations. Methodology: Different statistical approaches were used to evaluate HPV genotype competition, with subject and HPV DNA information coming from five epidemiological studies conducted among females in Canada and Brazil. These approaches involved: 1) construction of hierarchical logistic regression models for each vaccine-targeted genotype and analyses to explore whether infection with these genotypes may be associated with infection with other HPV genotypes; and 2) construction of Kaplan-Meier curves and Cox models to evaluate sequential acquisition and clearance of HPV genotypes according to HPV status with vaccine-targeted genotypes. To evaluate unmasking of HPV52 that may be caused by elimination of HPV16, we also reanalyzed 1000 cervical specimens (from the same five studies) plus an additional 200 anal specimens (from a Montreal study conducted among HIV infected males). These specimens, which were all HPV52 negative according to consensus PCR assays (200 specimens/study; 100 HPV16+/study) were retested using highly sensitive type-specific real-time HPV52 PCR.Results: In our pooled analyses comparing risk of infection with vaccine-targeted HPV genotypes according to infection with other genotypes (regression approach), only one negative association was observed (between HPVs 18 and 89), but was not statistically significant. Similarly, in our analyses comparing rates of acquisition or clearance of other HPV genotypes according to infection with vaccine-targeted genotypes (cohort approach), no statistically significant negative or positive associations were observed (once accounting for multiple comparisons), respectively. In our analyses of unmasking, presence of HPV16 was positively associated with HPV52 detection, particularly in the single study that included HIV infected males (adjusted OR=3.82, 95%CI: 1.19-12.26). Although substantial heterogeneity was observed across studies (P value=0.08), there was a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend=0.003).Conclusion: No clear or consistent evidence of genotype competition was observed across our regression or cohort analyses.…