Association between human papillomavirus and preterm delivery: A systematic review and meta-analysis

The lifetime prevalence of human papillomavirus infection (HPV) is estimated to be around 80% and it is the most common sexually transmitted infection. Despite being well known for its oncologic relevance, it has been associated with adverse pregnancy outcomes, though available evidence is contradicting. Previous meta-analyses involved articles which based HPV infection on Pap smear results, leading to a significant source of bias. Therefore, we aimed to assess the burden of genetically proven HPV infection on adverse pregnancy outcomes.

In our meta-analysis, pregnant women tested for HPV DNA were only considered eligible. We conducted a systematic search in three major databases (PubMed, Embase, and CENTRAL) on September 22, 2023. Cohort, cross-sectional, and case-control studies were eligible for the analysis. The exposed group consisted of HPV-infected patients. We assessed the odds ratios (OR) with a confidence interval (CI) of 95%. In order to reduce the heterogeneity, we performed subgroup analyses based on different strains (high risk HPV, HPV 16/18, study design). The study was prospectively registered on PROSPERO (CRD42022370228).

Our study involved 14 articles with 7008 women. A significant association was found between preterm delivery and HPV infection (OR: 1.94, CI: 1.31-2.87). No significant association was found when separately examining high-risk HPV-infected women (OR: 1.94, CI: 0.82-4.59), and HPV 16 or 18-infected women (OR: 2.08, CI: 0.50-8.63) in terms of preterm delivery. No significant association was found between spontaneous abortion and HPV infection (OR: 1.02, CI: 0.16-6.31).

Our analysis indicates an association between HPV infection and preterm delivery. It is imperative that future studies consider confounding variables more comprehensively. Additionally, the global implementation of HPV vaccination programs holds significance not only in oncology but also in obstetrics.