The researchers used data from the TriNetX research network, a large global health database, to assess this relationship. Adults diagnosed with HPV were 1:1 propensity score–matched with non-HPV individuals based on factors such as age, sex, comorbidities, and socioeconomic status.
The study tracked new diagnoses of major depressive disorder, bipolar disorder, and schizophrenia using ICD-10-CM codes. Cox proportional hazard models were employed to estimate hazard ratios, while Kaplan–Meier analyses were conducted to determine cumulative incidence rates over time.
The analysis led to the following findings:
- Adults aged 18 years and older with an HPV diagnosis had a 28% higher risk of developing major depressive disorder (HR 1.28) compared with those without HPV.
- The risk of developing bipolar disorder was 31% higher in individuals with HPV (HR 1.31).
- No significant association was observed between HPV infection and the onset of schizophrenia (HR 1.07).
- Women, younger adults, and individuals with sleep disorders were more susceptible to developing psychiatric conditions following an HPV diagnosis.
- These vulnerable subgroups showed stronger associations, indicating that biological, hormonal, or psychosocial factors may contribute to the increased psychiatric risk.
The authors emphasized that while HPV is primarily recognized for its role in causing cervical and other anogenital cancers, the potential neuropsychiatric implications of HPV infection are gaining increasing attention. The exact mechanisms underlying this association remain unclear but could involve immune dysregulation, inflammatory pathways, or stress responses triggered by chronic infection or the psychological burden of diagnosis.
Importantly, the study highlights the need for routine mental health screening and early intervention among individuals diagnosed with HPV, particularly women and those with preexisting vulnerabilities such as sleep disorders. The authors suggest that integrating psychological assessment into HPV care could improve overall health outcomes and quality of life for affected patients.
However, the researchers also noted certain limitations. Being a retrospective study, it could not establish causality, and potential confounding factors such as lifestyle, medication use, or undiagnosed psychiatric conditions could not be entirely ruled out. Despite these constraints, the study’s large sample size and robust analytical methods lend considerable strength to the findings.
The study provides compelling evidence that HPV infection may increase susceptibility to major depressive and bipolar disorders, reinforcing the importance of holistic care that addresses both physical and mental health aspects in individuals living with HPV.
"Further longitudinal and mechanistic studies are warranted to confirm these findings and explore the biological pathways linking HPV to mental health disorders," the authors concluded.
Reference:
Chang, C., Chu, J., Chang, C., Hsu, T., Hung, H., Su, J., Chen, J., & Gau, Y. (2025). New-Onset Major Depressive Disorder, Schizophrenia and Bipolar Disorder in People With Human Papillomavirus Diagnosis: A Population-Based Cohort Study. Journal of Medical Virology, 97(10), e70618. https://doi.org/10.1002/jmv.70618
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