Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Understanding the time-driven shifts of vaccine effectiveness against any and severe COVID-19 before and after the surge of Omicron variants within 2.5 years of vaccination: A meta-regression.

OBJECTIVES: The COVID-19 pandemic required rapid development of vaccines within a short period of time which did not allow to assess vaccine effectiveness (VE) in the long-term. METHODS: A computerized literature search was undertaken to identify eligible studies, with no language restrictions, published between 1 December 2020 and 30 June 2023. RESULTS: Out of a total of 27,597 publications, 761 studies were included. Early VE of 87.2% decreased to 55.1% after 9 months among populations fully immunized not only with mRNA (proxy mRNA) vaccines, and 66.3% decreased to 23.5% in populations immunized exclusively with non-mRNA vaccines. Protection against severe COVID-19 declined to 80.9% for proxy mRNA vaccines and 67.2% for non-mRNA vaccines. Omicron variants significantly diminished VE. Within 6-8 months of receiving a single booster of an mRNA vaccine, VE declined to 14.0% and 67.7% for any and severe COVID-19, respectively. Multiple mRNA booster doses restored protection that declined to 29.5% and 70.6% for any and severe COVID-19, respectively, within 5-7 months. CONCLUSION: Outcomes of this meta-regression underscore the evolving nature of COVID-19 in response to vaccination, dosing schedules, and emerging variants, and provide crucial insights for public health interventions and vaccination strategies.

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression.

OBJECTIVE: The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies. DESIGN: Meta-analysis and meta-regression. DATA SOURCES: A computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023. REVIEW METHODS: Included were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression. RESULTS: Out of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%. CONCLUSIONS: The outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results. PROSPERO REGISTRATION NUMBER: CRD42022353530.