Impact of Adjuvant Nonavalent HPV Vaccination on Viral Clearance in HPV-Positive Women With and Without Excisional Treatment: A Retrospective Cohort Study

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is the key driver of cervical carcinogenesis and post-treatment recurrence. Although excisional treatment effectively removes dysplastic tissue, it does not directly target viral persistence. While HPV vaccination is well established in primary prevention, its potential role as an adjuvant strategy in HPV-positive women, particularly with respect to viral clearance, remains incompletely defined. METHODS: This retrospective cohort study included HPV-positive women with at least 12 months of follow-up who were managed at a tertiary gynecology clinic. Patients were stratified according to HPV vaccination status with the nonavalent vaccine (Gardasil 9) and excisional treatment status with loop electrosurgical excision procedure (LEEP). HPV clearance at 12 months was defined as the primary outcome, while histological outcomes were evaluated as secondary and independent endpoints. Analyses were performed in the overall cohort and stratified by LEEP status. Multivariable logistic regression was used to identify factors independently associated with HPV persistence, adjusting for baseline disease severity and clinical covariates. RESULTS: A total of 935 HPV-positive women were included in the final analysis. Completion of the three-dose HPV vaccination schedule was associated with significantly higher HPV clearance rates at 12 months compared with no vaccination. This association was consistently observed in women who underwent LEEP as well as in those managed without excisional treatment. In multivariable analysis, HPV vaccination emerged as an independent protective factor against HPV persistence, whereas LEEP status itself was not independently associated with viral clearance after adjustment for baseline histological severity. Histological outcomes differed according to baseline disease severity and did not demonstrate a direct one-to-one relationship with HPV clearance. CONCLUSIONS: Adjuvant vaccination with the nonavalent HPV vaccine is independently associated with increased HPV clearance in HPV-positive women at 1-year follow-up, irrespective of excisional treatment status. HPV clearance and histological regression represent related but distinct biological processes and should be evaluated as independent outcomes. These findings support a broader role for HPV vaccination beyond primary prevention and suggest potential clinical benefit of vaccination as an adjunctive strategy in the management of HPV-positive women.