This review assessed whether women who receive prophylactic human papillomavirus (HPV) vaccination have a lower incidence of persistent HPV infection and pre-cancerous cervical lesions than women who are not vaccinated. The authors concluded that there is convincing evidence that prophylactic HPV vaccination is efficacious for the prevention of vaccine type-specific HPV infection and pre-cancerous cervical disease. The authors’ conclusions reflect the evidence presented and are likely to be reliable.

To determine whether women who receive prophylactic human papillomavirus (HPV) vaccination have a lower incidence of persistent HPV infection and pre-cancerous cervical lesions than women who are not vaccinated.

MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane CENTRAL Register and the Cochrane Library were searched; the search dates covered 1950 to 2007. In addition, bibliographies of all included studies were reviewed, as were narrative reviews, clinical trial registries, Google Scholar, public health announcements, selected conference proceedings (between 2004 and 2007) and information from vaccine manufacturers, for unpublished data or ongoing RCTs.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies of any vaccine against HPV that contained at least one oncogenic strain of the virus, used prophylactically, were eligible for inclusion. Any dosing regimen was accepted. Studies with reports of therapeutic vaccination were excluded, as were those not designed to address outcomes related to vaccine efficacy against oncogenic HPV strains. Comparators were required to be either placebo or ‘no HPV vaccination’.

Participants included in the review

Studies in women receiving the HPV vaccine were included. There were no exclusions on the basis of age or other demographic characteristics. The women in the included studies had a mean age of 20 years (age range: 15 to 25).

Outcomes assessed in the review

The primary outcome of interest was the frequency of high-grade cervical lesions (defined as high-grade squamous intraepithelial lesion, or grade 2 or 3 cervical intraepithelial neoplasia). The secondary outcomes reported included persistent HPV infection, low-grade cervical lesions, external genital lesions, adverse events and death.

How were decisions on the relevance of primary studies made?

The two primary reviewers independently screened studies for relevance. Any discrepancies were resolved through consultation with a third-party reviewer.

Two reviewers independently assessed validity according to the Jadad checklist, plus a separate assessment of allocation concealment. Blinding was not undertaken for the quality assessment process.

The two primary reviewers independently extracted the data from the included studies using a data abstraction form developed, and piloted, by both primary reviewers. Data were extracted on baseline demographic characteristics, length of follow-up, and primary and secondary outcomes.

How were the studies combined?

Where studies were deemed sufficiently clinically similar, a meta-analysis was used. Pooled estimates, and their confidence intervals (CIs), were estimated through a fixed-effect model.

How were differences between studies investigated?

Differences between the studies were evaluated through examination of the overlap of CIs between the studies and using the I-squared test.

Six RCTs were included, totalling 40,323 participants (range: 552 to 18,644).

The included RCTs met all five of the Jadad validity criteria.

High-grade cervical lesions (5 studies): the pooled, overall Peto odds ratio (OR) was 0.14 (95% CI: 0.09, 0.21) in the per-protocol analysis and 0.52 (95% CI: 0.43, 0.63) in the modified intention-to-treat meta-analysis.

Any cervical lesions (5 studies): the pooled, overall Peto OR was 0.13 (95% CI: 0.09, 0.20) in the per-protocol analysis and 0.36 (95% CI: 0.29, 0.45) in the modified intention-to-treat meta-analysis.

The results for other secondary outcomes were reported in the paper.

For women aged between 15 and 25 years of age who had not previously been infected with vaccine-type HPV strains, prophylactic HPV vaccination would, based on the results of this review, appear to be highly successful at preventing HPV infection and pre-cancerous cervical disease.

The review question was clear and was supported by appropriate inclusion criteria relating to the participants, interventions and study designs. Attempts were made to identify all of the relevant literature by searching a range of electronic databases and other sources. Validity was assessed against published criteria. Appropriate methods were used to combine the studies and to control for statistical differences between them. The authors’ conclusions would appear to be representative of the evidence within the selected studies and are likely to be reliable.

Practice: The authors stated that there is convincing evidence that prophylactic HPV vaccination is efficacious for the prevention of vaccine type-specific HPV infection and pre-cancerous cervical disease. The impact appears to be greatest in women aged between 15 and 25 years who receive all three vaccine doses, who have had no more than six lifetime sexual partners, and have no prior abnormal results from Pap screening.

Research: Long-term follow-up studies should be undertaken to confirm reductions in cervical cancer incidence and mortality.

Not stated.

This additional published commentary may also be of interest.
Muresan J. Review: vaccines against human papillomavirus prevent cervical cancer precursors in young women. Evid Based Nurs 2008;11:11.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.