Introduction:
Observational studies suggest HIV and human papillomavirus (HPV) infections may have
multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV
acquisition and clearance, and the influence of HPV on HIV acquisition.
Methods:
We performed meta-analytic systematic reviews of longitudinal studies of HPV incidence
and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We
pooled relative risk (RR) estimates across studies using random-effect models. I
2
statistics and
subgroup analyses were used to quantify heterogeneity across estimates and explore the influence
of participant and study characteristics including study quality. Publication bias was examined
quantitatively with funnel plots and subgroup analysis, as well as qualitatively.
Results and discussion:
In
review 1, 37 publications (25 independent studies) were included in the
meta-analysis. HPV incidence (pooled RR=1.55, 95%CI 1.29-1.88; heterosexual males: pooled
RR=1.95, 95%CI 1.62, 2.34; females: pooled RR=1.63, 95%CI 1.26-2.11; men who have sex with men:
pooled RR=1.36, 95%CI 1.01-1.82) and high-risk HPV incidence (pooled RR=2.20, 95%CI 1.90-2.54)
was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate
(pooled RR=0.53, 95%CI 0.42-0.67) was approximately halved. In
review 2, 14 publications (11
independent studies) were included in the meta-analysis. HIV incidence was almost doubled (pooled
RR=1.91, 95%CI 1.38-2.65) in the presence of prevalent HPV infection. There was more evidence of
publication bias in review 2, and somewhat greater risk of confounding in
studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for
review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward
the null.
Conclusions:
These results provide evidence for synergistic HIV and HPV interactions of clinical and
public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and
HIV at the population level in high prevalence settings. Our estimates of association are useful for
mathematical modelling. Although observational studies can never perfectly control for residual
confounding, the evidence presented here lends further support for the presence of biological
interactions between HIV and HPV that have a strong plausibility.