Methods
With the aim to identify all publications in which a HPV vaccination was
given in addition to the standard treatment for cervical dysplasia, we
conducted an extensive search with a medical librarian of the literature
from inception till 1th of august 2019 using the following databases:
Pubmed, Medline and the Cochrane library. The search strategies
contained various combinations of keywords and MeSH headings:
Papillomavirus vaccines, HPV vaccine, human papilloma virus vaccination,
Papillomaviridae, HPV, LEEP, conization, CIN, surgical therapy and
biopsy. The search strategy is presented in appendix S1.
Eligible studies were human studies published in English or Dutch,
without any restriction on study design. All articles that described the
effect of vaccination in addition to a surgical treatment such as LEEP,
conization, cone biopsy or other surgical therapy for cervical
intra-epithelial neoplasia (CIN I-II-III) or high grade squamous
intraepithelial lesion (HSIL) could be included. No limitation were made
on age, number of sexual partners, HPV-type or prior treatment for HPV
related diseases. Studies on HIV were excluded.
The titles and abstracts of all the citations retrieved by the searches
were screened for relevance independently and separately by two of the
authors (RL and WH). The full texts of the resulting articles were
assessed on their relevance to this review. In case of disagreement, the
third author (HB) assessed the relevance as well. The references of
selected publications were checked on relevant other publications. The
following details were sourced: Author, year of publication, age, study
type, sample size, recurrence rate of cervical dysplasia after treatment
and vaccination with a HPV vaccine. A random effect model is used to
calculate the pooled effect size, anticipating heterogeneity between
studies. Categorical data were summarized using the Mantel-Haenszel Risk
Ratio (RR) with 95% confidence intervals (CI). Heterogeneity was
calculated using the I² statistic. Meta-analysis was performed using the
software “Review Manager” version 5.3 from the Cochrane Collaboration.
Risk of bias was assessed using the modified Downs and Black (D&B)
scale. The Downs and Black scale is also suitable for non-randomised
trials (20). We used the checklist to score the reporting, the internal
validity and external validity of the eligible studies. A High score
indicates a better methodological quality. A score of 19 or higher
indicates a high quality of the study as used in other studies (21).
Whereas a score of <19 considered to be of low quality (See
online supplementary table S2). The quality assessments of the included
studies were used to categorize the level of evidence. We scored all
studies below 19 and were subsequently methodologic of low quality.