Exposure to Per- and Polyfluoroalkyl Substances and Risk of Reproductive System Cancers: A Systematic Review and Meta-Analysis

Abstract Background Per- and polyfluoroalkyl substances (PFAS), a class of highly stable synthetic organic compounds, have been detected ubiquitously in human biological samples, raising significant concerns about their safety. The aim of this study was to investigate whether PFAS exposure is associated with higher risk of reproductive cancers. Methods Three databases were searched from inception to August 2025. Case-control or cohort studies that examined the association between serum/plasma exposure to five PFAS (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], perfluorohexane sulfonic acid [PFHxS], perfluorononanoic acid [PFNA] and perfluorinated sulfonic acids [PFSA]) and reproductive system cancers, including female reproductive system (breast and ovarian cancers) and male reproductive system (prostate and testicular cancers), were included. Results 21 case-control studies were included. Pooled adjusted odds ratios (aORs) showed no significant association between PFAS exposure and female reproductive cancers. When comparing highest to lowest exposure, pooled aORs were 1.09 (95% CI: 0.83–1.43) for PFOA, 1.11 (0.82–1.48) for PFOS, 0.96 (0.68–1.36) for PFHxS, 1.11 (0.79–1.56) for PFNA, and 1.14 (0.46–2.80) for PFSA. PFOS showed a marginal positive association with male reproductive cancers (1.25, 1.02–1.52), whereas PFOA showed no association (0.87, 0.65–1.17). Notably, PFNA per ln-unit increase was significantly associated with female reproductive cancers (1.39, 1.07–1.79) in sensitivity analyses. Conclusions Overall, serum PFAS exposure was not significantly associated with female reproductive cancers, though PFNA showed a positive association in sensitivity analysis. PFOS may be associated with increased risk for male reproductive cancers.