欧洲疾控中心-对非HIV免疫功能低下个体接种HPV疫苗的疗效_有效性_免疫原性和安全性的系统评价和荟萃分析（英）-2025_91页_2mb

HPV Vaccination in Non-HIV Immunocompromised Individuals: A Systematic Review and Meta-Analysis

Core Content

This report, commissioned by the European Centre for Disease Prevention and Control (ECDC), presents a systematic review and meta-analysis on the efficacy, effectiveness, immunogenicity, and safety of human papillomavirus (HPV) vaccination in non-HIV immunocompromised individuals. The findings are based on 27 studies, including 23 non-randomised studies of interventions (NRSI) and 6 single-arm studies, published between 2013 and 2023. The studies were conducted in Europe, North America, Australia, South America, and Asia.

The review focuses on three main comparisons:

1. Vaccinated immunocompromised group vs. unvaccinated immunocompromised control group (Comparison 1)
2. Vaccinated immunocompromised group vs. other vaccinated immunocompromised control group with different immune conditions (Comparison 2)
3. Vaccinated immunocompromised group vs. vaccinated healthy control group (Comparison 3)

The outcomes of interest include precancerous or cancerous lesions, HPV infection, immunogenicity (measured by seropositivity and geometric mean ratios [GMRs]), and safety (serious adverse events [SAEs] and local/systemic adverse events).

Main Findings

Efficacy and Effectiveness

• Patient-relevant outcomes (e.g., CIN 2+, CIN 3+) were assessed in only one study (a case-control study), which reported very low certainty of evidence.
• The adjusted rate ratio for CIN 2+ was 0.96 (0.68 to 1.37), and for CIN 3+ it was 0.96 (0.54 to 1.70), indicating no significant difference in the risk of cervical cancer between vaccinated and unvaccinated immunocompromised individuals.
• There is insufficient data to determine the effectiveness of HPV vaccines in preventing HPV-related cancers in non-HIV immunocompromised individuals.

Immunogenicity

• Seropositivity rates and GMRs were generally high across all immunocompromised groups, often reaching 100% or near 100%.
• For comparison 3, seropositivity rates were similar between vaccinated immunocompromised individuals and vaccinated healthy controls, with low to very low certainty of evidence.
• For comparison 2, the results suggested little to no difference in seropositivity rates for HPV 16 between groups, while HPV 18 showed some variation, with very low certainty of evidence.

Safety

• SAEs were rare and not attributed to the HPV vaccine by study authors.
• Local adverse events (e.g., pain, induration, erythema, edema) and systemic adverse events (e.g., headache, fatigue, nausea) were reported across all vaccine types, but these were generally mild and common in both vaccinated and unvaccinated groups.
• Single-arm studies provided limited safety data, but the overall pattern suggested general safety of HPV vaccines in immunocompromised populations.

Key Information

Limitations

• Clinical heterogeneity due to variability in participant groups limited the ability to perform subgroup and sensitivity analyses.
• Low to very low certainty of evidence was observed for most outcomes, primarily due to serious risk of bias and considerable imprecision.
• Correlates of protection (e.g., for HPV-associated cancers) are unclear, and assay standardisation for antibody measurement is lacking.

Factors Influencing Immunogenicity

• Immunocompromised conditions (e.g., autoimmune diseases, cancer, organ transplants) and immunosuppressive treatments may influence vaccine response.
• Timing of vaccination, prior HPV exposure, and age/sex differences may also affect immunogenicity outcomes.

Recommendations

• Further research is needed to better understand the effectiveness of HPV vaccines in non-HIV immunocompromised individuals.
• Studies should focus on standardised assays, long-term follow-up, and specific subgroups (e.g., organ transplant recipients, cancer survivors).
• Immunogenicity data should be interpreted with caution due to low certainty and variability in outcomes.

Conclusion

HPV vaccination in non-HIV immunocompromised individuals appears to be immunogenic and generally safe, but the evidence for efficacy and effectiveness is limited. Most findings are based on immunogenicity and safety data from studies comparing vaccinated immunocompromised individuals to other vaccinated or unvaccinated groups. The certainty of evidence is low to very low, and further studies are required to clarify the protective benefits of HPV vaccines in these populations.