Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta‐analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status

Abstract

IntroductionObservational 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.MethodsWe 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 DiscussionIn review 1, 37 publications (25 independent studies) were included in the meta‐analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high‐risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 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 to 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.ConclusionsThese 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.

Human papilloma virus-related premalignant and malignant lesions of the cervix and anogenital tract in immunocompromised women

“…The most-studied subtypes that are linked with the creation of anogenital malignancies are hrHPV types 16 and 18, and they are said to be responsible for approximately 70% of cervical cancers and precancerous lesions [7]. Another 20% of cervical cancers are related to hrHPV types 31, 33, 35, 45, 52 and 58 [8].…”

“…These findings are supported by those of the meta-analysis by Looker et al, which proved that in the presence of HIV infection, the risk of HPV acquisition doubles, and for clearance halves, especially with a decline in the CD 4 cell count. A threatening observation is that similarly to other sexually transmitted diseases, HPV infection itself may promote the acquisition of HIV infection [7].…”

Interplay between competitive and cooperative interactions in a three-player pathogen system

“…While interfering with each other, strains also interact with other pathogens co-circulating in the same population. Tuberculosis [1], HPV [9] and P. falciparum [10], for example, appear to be facilitated by HIV, whereas S. pneumoniae benefits from some bacterial infections, e.g. Moraxella catarrhalis, and is negatively associated to others such as S. aureus [11,12].…”

ART is key to clearing oncogenic HPV genotypes (HR-HPV) in anal mucosa of HIV-positive MSM

“…ASCC has been associated with persistent infection by high-risk oncogenic HPV (HR-HPV) genotypes, which increases the expression of oncoproteins E6 and E7, activates the cell cycle, inhibits apoptosis, and allows the accumulation of damaged DNA [3]. HIV and HPV share similar risk factors and interact in various ways to infect the anal-genital area; their interaction has been reported to double the risk of HPV acquisition and halve the clearance rate among seropositive individuals in comparison to the general population [4].…”

“…Given the lack of clarity on factors associated with HPV clearance in anal mucosa of HIV +MSM patients [4] and the consequent absence of specific recommendations, the main objectives of this study were to determine the clearance rate of oncogenic HPV genotypes and associated factors and to explore their possible relationship with the incidence of HSIL and ASCC in the anal mucosa of a prospectively enrolled cohort of HIV+MSM. Further objectives were to study: risk factors for HPV infection; genotype distribution as a function of histology; and correlations among cytology, HPV polymerase chain reaction (PCR), and histological findings in the anal mucosa.…”