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. 2011 Apr 1;203(7):910-20.
doi: 10.1093/infdis/jiq139.

Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease

Anil K Chaturvedi  1 , Hormuzd A Katki, Allan Hildesheim, Ana Cecilia Rodríguez, Wim Quint, Mark Schiffman, Leen-Jan Van Doorn, Carolina Porras, Sholom Wacholder, Paula Gonzalez, Mark E Sherman, Rolando Herrero; CVT Group
Collaborators, Affiliations

Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease

Anil K Chaturvedi et al. J Infect Dis. .

Abstract

Objective: We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease.

Methods: Sexually active women (n=5,871) in the NCI-sponsored Costa Rica HPV Vaccine Trial's prevaccination enrollment visit were analyzed. Genotyping for 25 HPVs was performed using SPF(10)/LiPA(25). We calculated odds ratios (ORs) to assess coinfection patterns for each genotype with 24 other genotypes. These ORs were pooled and compared with pair-specific ORs to identify genotype combinations that deviated from the pooled OR. We compared risk of CIN2+/HSIL+between multiple and single infections and assessed additive statistical interactions.

Results: Of the 2478 HPV-positive women, 1070 (43.2%) were infected with multiple types. Multiple infections occurred significantly more frequently than predicted by chance. However, this affinity to be involved in a coinfection (pooled OR for 300 type-type combinations=2.2; 95% confidence interval [CI]=2.1-2.4) was not different across HPV type-type combinations. Compared with single infections, coinfection with multiple α9 species was associated with significantly increased risk of CIN2+(OR=2.2; 95% CI=1.1-4.6) and HSIL+(OR=1.6; 95% CI=1.1-2.4). However, disease risk was similar to the sum of estimated risk from individual types, with little evidence for synergistic interactions.

Conclusions: Coinfecting HPV genotypes occur at random and lead to cervical disease independently.

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Figures

Figure 1.
Figure 1.
Log odds ratios and 95% confidence intervals for HPV16 (A), HPV18 (B), HPV6 (C), and HPV11 (D) for coinfection with 24 other HPV types are shown. The vertical solid line represents the odds ratio pooled across the 24 individual pair-specific odds ratios. The dashed vertical line represents the null log odds ratio of .0. Although odds ratios for some type-type combinations were significantly different from the pooled odds ratio at the .05 level, these associations did not retain statistical significance at a Bonferroni-corrected P-value threshold of P < .002, with the exception of coinfection of HPV11 with HPV53.
Figure 1.
Figure 1.
Log odds ratios and 95% confidence intervals for HPV16 (A), HPV18 (B), HPV6 (C), and HPV11 (D) for coinfection with 24 other HPV types are shown. The vertical solid line represents the odds ratio pooled across the 24 individual pair-specific odds ratios. The dashed vertical line represents the null log odds ratio of .0. Although odds ratios for some type-type combinations were significantly different from the pooled odds ratio at the .05 level, these associations did not retain statistical significance at a Bonferroni-corrected P-value threshold of P < .002, with the exception of coinfection of HPV11 with HPV53.
Figure 2.
Figure 2.
(A) Log odds ratios for 300 type-type combinations across 25 HPV genotypes. The vertical line represents the null log odds ratio of .0. (B) Pooled odds ratios across 300 individual odds ratios as well as pair-specific odds ratios that differ significantly from the pooled odds ratio at a Bonferroni-corrected P-value threshold of P < .0001.
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References

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