BACKGROUND AND PURPOSE:

• Henschke et al. (Cochrane Database of Systematic Reviews, 2025) assessed population-level effects of HPV vaccination programs on HPV-related disease and harms from vaccination

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Population-level studies that compared outcomes before and after the introduction of the HPV vaccine
  • Individual-level nonrandomized comparative studies
• Study design
  • Risk of bias was assessed with tools appropriate for included study types
  • Certainty of evidence was assessed with GRADE criteria
  • Meta-analysis was adjusted for confounding, with a focus on those receiving HPV vaccination at or before the age of 16 years
• Primary outcomes
  • Cervical cancers and other cancers
  • High-grade pre-cancer lesions
  • Adverse events

RESULTS:

• 225 studies | 132 million individuals
  • Cohort studies: 86 | Case-control studies: 4 | Cross-sectional studies: 46 | Pre-post vaccination studies: 69 | RCT extensions: 5 | Case series: 2 | ≥1 type of analysis: 13
  • Reported on females only: 177 | Reported on males only: 11 | Reported on both: 37
  • Risk of bias was moderate to critical

Cervical Cancer

• HPV vaccination likely reduces the incidence of cervical cancer
  • 20 studies | Moderate certainty
• From cohort studies. There was a reduced risk of cervical cancer following HPV vaccination in the long term
  • Risk ratio (RR) 0.37 (95% CI, 0.25 to 0.56) | I2=88%
  • 5 studies | 4,390,23 females
• There was a significant interaction with age at vaccination, with a greater risk reduction in younger people
  • Vaccinated ≤16 years of age
    • RR 0.20 (95% CI, 0.09 to 0.44) | I²=69%
    • 4.54 million person-years
• Other studies that reported no cases of cervical cancer in HPV vaccination groups: 6
• Other studies that reported a reduction in cervical cancer incidence with HPV vaccination: 8

CIN3+

• HPV vaccination likely reduces the incidence of CIN3+
  • 23 studies | Moderate certainty
• In cohort studies, vaccination at or before 16 years of age reduced CIN3+ incidence in the long term
  • RR 0.26 (95% CI, 0.12 to 0.56) | I²=80%
  • 2 cohort studies | 1.5 million females
• Other studies that reported a decreased risk of CIN3+ with vaccination: 7
• Other studies that reported no difference in the risk of CIN3+: 1

CIN2+

• HPV vaccination likely reduces the incidence of CIN2+
  • 37 studies | Moderate certainty
• In cohort studies with females vaccinated ≤16 years, a reduction in risk was seen in the
  • Medium term
    • RR 0.59 (95% CI, 0.54 to 0.65) | I2=0%
    • 2 cohort studies | 233,468 females
  • Long term
    • RR 0.38 (95% CI, 0.31 to 0.45) | I2=64%
    • 5 cohort studies | 6,455,176 females

Anogenital Warts

• HPV vaccination likely reduces the incidence of anogenital warts
  • 47 studies | Moderate certainty
• In cohort studies, the pooled impact of HPV vaccination on rates of anogenital warts indicated a reduction in the
  • Medium term
    • RR 0.53 (95% CI, 0.37 to 0.77) | I2=98%
    • 4 cohort studies | 6,430,295 females | 313 males
  • Long term
    • RR 0.47 (95% CI, 0.36 to 0.61) | I2=99%
    • 13 cohort studies | 5,802,969 females and males
• Other studies that reported a decrease in anogenital warts with HPV vaccination: 23
• Other studies that reported no difference in anogenital warts with HPV vaccination: 6

Other Cancers

• There was little evidence on the effect of HPV vaccination on adenocarcinoma in situ
  • 3 studies | Very low certainty
• There was also little evidence on the effect of HPV vaccination on vulval cancer
  • 5 studies | Very low certainty

Adverse Events From Vaccination

• HPV vaccination was likely not associated with an increased risk of
  • Postural orthostatic tachycardia syndrome
  • Chronic fatigue syndrome/myalgic encephalomyelitis
  • Paralysis
  • Complex regional pain syndrome
  • Premature ovarian failure
  • Infertility or sexual activity
• HPV vaccination may not be associated with an increased risk of Guillain-Barré syndrome
  • Low certainty

CONCLUSION:

• HPV vaccination reduces the risk of cervical cancer and high-grade CIN
  • Benefits appear to be greater when vaccination occurs earlier in adolescence
• The authors state

There are now long‐term outcome data from different countries and from different study designs that consistently report a reduction in the development of high‐grade CIN and cervical cancer in females vaccinated against HPV in early adolescence

There is evidence that HPV vaccination does not increase the risk of the most common adverse events reported on social media

Learn More – Primary Sources:

Effects of human papillomavirus (HPV) vaccination programmes on community rates of HPV-related disease and harms from vaccination