Randomization Modeling to Ascertain Clustering Patterns of Human Papillomavirus Types Detected in Cervicovaginal Samples in the United States

Detection of multiple human papillomavirus (HPV) types in the genital tract is common. Associations among HPV types may impact HPV vaccination modeling and type replacement. The objectives were to determine the distribution of concurrent HPV type infections in cervicovaginal samples and examine type-specific associations. We analyzed HPV genotyping results from 32,245 cervicovaginal specimens collected from women aged 11 to 83 years in the United States from 2001 through 2011. Statistical power was enhanced by combining 6 separate studies. Expected concurrent infection frequencies from a series of permutation models, each with increasing fidelity to the real data, were compared with the observed data. Statistics were computed based on the distributional properties of the randomized data. Concurrent detection occurred more than expected with 0 or ≥3 HPV types and less than expected with 1 and 2 types. Some women bear a disproportionate burden of the HPV type prevalence. Type associations were observed that exceeded multiple hypothesis corrected significance. Multiple HPV types were detected more frequently than expected by chance and associations among particular HPV types were detected. However vaccine-targeted types were not specifically affected, supporting the expectation that current bivalent/quadrivalent HPV vaccination will not result in type replacement with other high-risk types.