Prevalence and clustering patterns of human papillomavirus genotypes in multiple infections

Prevalence of multiple human papillomavirus (HPV) infections, involvement of specific HPV phylogenetic clades in multiple infections, and clustering patterns of multiple infections at the clade level were assessed in 854 HIV (-) and 275 HIV (+) women cross-sectionally. Reverse line blot assay was used to detect 27 HPV genotypes. Involvement of specific clades in coinfections and clustering patterns were assessed using HPV clade/genotype as the unit of analyses. Expected frequencies assuming independence for all possible clade combinations in two-genotype infections were derived using a multinomial expansion and comparisons of observed and expected frequencies were done using a composite goodness-of-fit test. In all, 100 two-genotype infections were detected; 61 in HIV (-) and 39 in HIV (+) women. Clade A9 (HPV types 16, 31, 33, 35, 52, and 58) was significantly less likely to be involved in multiple infections compared with all other clades (55.2% versus 64.6%; adjusted odds ratios, 0.68; 95% confidence interval, 0.48-0.95). Observed patterns for all possible clade combinations (among HPV clades A3, A5, A6, A7, A9, and A10) in two-genotype infections did not significantly differ from those expected in the entire sample, across HIV, Pap smear, and age strata (all goodness-of-fit exact P > 0.20). These results indicate that clade A9 is less likely to be involved in multiple infections and that HPV genotypes predominantly establish multiple infections at random, with little positive/negative clustering for either phylogenetically related or unrelated types. The current method of analysis affords the opportunity to test clustering of a large number of HPV genotype/clade combinations at nominal alpha levels.