Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

Research output: Contribution to journalReviewResearchpeer-review

  1. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Benefits and harms of the human papillomavirus (HPV) vaccines

    Research output: Book/ReportPh.D. thesisResearch

  3. Methodology Flaws and Implications of a Complementary Medicine Study

    Research output: Contribution to journalComment/debateResearch

  4. Increased incidence of cervical cancer in Sweden: an unlikely link with human papillomavirus (HPV) vaccination

    Research output: Contribution to journalComment/debateResearchpeer-review

  5. The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias

    Research output: Contribution to journalReviewResearchpeer-review

View graph of relations

OBJECTIVE: To assess the benefits and harms of the human papillomavirus (HPV) vaccines.

DATA SOURCES: Clinical study reports obtained from the European Medicines Agency and GlaxoSmithKline from 2014 to 2017.

ELIGIBILITY CRITERIA: Randomised trials that compared an HPV vaccine with a placebo or active comparator in healthy participants of all ages.

APPRAISAL AND SYNTHESIS: Two researchers extracted data and judged risk of bias with the Cochrane tool (version 2011). Risk ratio (RR) estimates were pooled using random-effects meta-analysis.

OUTCOMES: Clinically relevant outcomes in intention to treat populations-including HPV-related cancer precursors irrespective of involved HPV types, treatment procedures and serious and general harms.

RESULTS: Twenty-four of 50 eligible clinical study reports were obtained with 58,412 pages of 22 trials and 2 follow-up studies including 95,670 participants: 79,102 females and 16,568 males age 8-72; 393,194 person-years; and 49 months mean weighted follow-up. We judged all 24 studies to be at high risk of bias. Serious harms were incompletely reported for 72% of participants (68,610/95,670). Nearly all control participants received active comparators (48,289/48,595, 99%). No clinical study report included complete case report forms. At 4 years follow-up, the HPV vaccines reduced HPV-related carcinoma in situ (367 in the HPV vaccine group vs. 490 in the comparator group, RR 0.73 [95% confidence interval, CI, 0.53 to 1.00], number needed to vaccinate [NNV] 387, P = 0.05, I2 = 67%) and HPV-related treatment procedures (1018 vs. 1416, RR 0.71 [95% CI 0.63 to 0.80], NNV 75, P < 0.00001, I2 = 45%). The HPV vaccines increased serious nervous system disorders (exploratory analysis: 72 vs. 46, RR 1.49 [1.02 to 2.16], number needed to harm [NNH] 1325, P = 0.040, I2 = 0%) and general harms (13,248 vs. 12,394, RR 1.07 [95% CI 1.03 to 1.11], NNH 51, P = 0.0002, I2 = 77%) but did not significantly increase fatal harms (45 vs. 38, RR 1.19 [95% CI 0.65 to 2.19], P = 0.58, I2 = 30%) or serious harms (1404 vs. 1357, RR 1.01 [95% CI 0.94 to 1.08], P = 0.79, I2 = 0%).

CONCLUSION: At 4 years follow-up, the HPV vaccines decreased HPV-related cancer precursors and treatment procedures but increased serious nervous system disorders (exploratory analysis) and general harms. As the included trials were primarily designed to assess benefits and were not adequately designed to assess harms, the extent to which the HPV vaccines' benefits outweigh their harms is unclear. Limited access to clinical study reports and trial data with case report forms prevented a thorough assessment.

SYSTEMATIC REVIEW REGISTRATION: CRD42017056093. Our systematic review protocol was registered on PROSPERO in January 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf. Two protocol amendments were registered on PROSPERO on November 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf. Our index of the HPV vaccine studies was published in Systematic Reviews in January 2018: https://doi.org/10.1186/s13643-018-0675-z. A description of the challenges obtaining the data was published in September 2018: https://doi.org/10.1136/bmj.k3694.

Original languageEnglish
JournalSystematic Reviews
Volume9
Issue number1
Pages (from-to)43
ISSN2046-4053
DOIs
Publication statusPublished - 28 Feb 2020

ID: 59639389