BACKGROUND AND PURPOSE:

• Human papillomavirus (HPV) vaccination becomes less cost-effective after women reach age 26
• However, Women >26 years who are at high risk of HPV infection and undergoing surgical treatment for CIN may benefit from adjuvant HPV vaccination
• Kechagias et al. (BMJ, 2022) explored the efficacy of HPV vaccination among individuals undergoing local surgical treatment for preinvasive genital disease

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • All studies that reported on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated
• Study design
  • For meta-analysis, only included studies that also reported results from non-vaccinated cohort
  • For primary outcome, data from observational studies and RCTs were pooled if they included efficacy of vaccination when given shortly before, at the time of, or up to 12 months after the local surgical treatment
  • Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model
  • GRADE criteria used to assess evidence quality
• Primary outcome
  • Risk of recurrence for CIN2+ after local surgical treatment
• Secondary outcomes
  • Risk of HPV infection
  • Risk of other lesions related to HPV infection

RESULTS:

• 22 studies
  • 18 with a non-vaccinated control group were used in meta-analysis
• Risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated
  • RR 0.43 (95% CI, 0.30 to 0.60)
  • Median follow-up: 36 (IQR, 24 to 43.5) months
  • 11 studies | 19,909 participants
• Effect estimate was stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18
  • RR 0.26 (95% CI, 0.16 to 0.43)
  • 6 studies | 1879 participants
• Confidence in evidence ranged from very low to moderate
  • Likely due to publication bias and inconsistency in the studies included
• The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large
  • RR 0.28 (95% CI, 0.01 to 6.37)
  • 3 studies | 17,757 participants
• Evidence of benefit was lacking for recurrence of
  • Vulvar, vaginal, and anal intraepithelial neoplasia
  • Genital warts
  • Persistent and incident HPV infections

CONCLUSION:

• HPV vaccination might reduce the risk of CIN recurrence in individuals treated with local surgical excision, especially if the disease is related to HPV16 or HPV18
• The number of studies and participants for non-cervical intraepithelial neoplasia and warts was low
• High quality RCTs are needed to establish effectiveness of HPV vaccination in individuals undergoing treatment for HPV-related diseases
• The authors state

The NOVEL (Nonavalent Prophylactic HPV Vaccine (Gardasil 9) After Local Conservative, NCT03979014) trial, an ongoing, large, appropriately powered randomised controlled trial, is expected to report results and give further insight on the effect of Gardasil 9 on persistent incident, recurrent, and prevalent HPV infections and cost effectiveness

If the study reports benefit, the results could be applicable to women with multifocal disease, other diseases related to HPV infection, and individuals with a diagnosis of malignancies related to HPV infection

Learn More – Primary Sources:

Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis

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England’s Early HPV Vaccination Program Substantially Reduced Incidence of Cervical Cancer and CIN3

Beyond High-Risk Lesions: HPV Vaccination and Impact on Invasive Cervical Cancer Risk