Immunosuppression as an associated risk factor for high-grade cervical lesions: a comparative study of cytology, HPV, and histopathology

Background Persistent high-risk human papillomavirus (hrHPV) infection is the main cause of cervical carcinogenesis, and impaired immune surveillance may increase the risk of viral persistence and progression to high-grade lesions. This study aimed to evaluate the association between immunosuppression and high-grade cervical lesions (CIN2+) and to examine its association with HPV status, cytological findings, and histopathological outcomes. Methods This retrospective comparative cohort study included women evaluated with cervical cytology, HPV testing, colposcopy, and/or histopathology between 2019 and 2024 at two participating centers. After exclusions, 370 women were analyzed, including 313 immunocompetent controls and 57 immunosuppressed patients. HIV-infected women were excluded. The primary outcome was CIN2 + . Logistic regression analysis was performed to evaluate associations with high-grade cervical disease. Results Overall HPV positivity was similar between groups, but immunosuppressed women had a significantly higher prevalence of hrHPV infection. Endocervical curettage (ECC) was performed more frequently in the immunosuppressed group, and ECC positivity was also higher. Final histopathology showed fewer normal findings in immunosuppressed women, with numerically higher rates of CIN2, CIN3, and cancer. In multivariable analysis, immunosuppression remained associated with CIN2 + after adjustment (adjusted OR 1.7, 95% CI 1.0-3.0, p = 0.04). HPV16, multiple HPV infection, and HSIL cytology were also associated with CIN2 + in the adjusted model. Exploratory subgroup estimates for renal transplantation and selected immunosuppressive therapies were based on small samples and should be interpreted cautiously. Conclusion Immunosuppression was associated with a higher risk of high-grade cervical lesions and a less favorable cervical disease profile, supporting closer surveillance in this population.