ReviewIncreased risk of high grade cervical squamous intraepithelial lesions in systemic lupus erythematosus: A meta-analysis of the literature
Introduction
The prognosis of systemic lupus erythematosus (SLE) has improved constantly over the last decades, due to advances in therapeutic modalities and more judicious use of existing therapies, in particular steroids and cytotoxic agents. However, patients with SLE still carry a heavy burden of morbidity owing to organ damage as well as a significant mortality due to infections and cancer. Compared to the general population, the risk of cancer is increased by 15% in SLE [1], [2] and the incidence of virus-induced cancer appears to be particularly high in SLE patients [3]. In a prospective Canadian cohort study [4], the risk of cervical cancer, which was mainly carcinoma in situ, was increased with a standardized incidence ratio (SIR) of 8.15 (95%CI: 1.63–23.81). The causal role of HPV infection in cervical cancers has been firmly established and HPV types 16 and 18 are considered as the causative agents of 70% of cervical cancers [5]. It is therefore crucial to decide whether SLE patients should benefit from a specific gynecological follow-up, including either HPV vaccines against HPV types 16 and 18 or cervical cancer screening, or both. Few studies, mostly performed on small samples, have evaluated the rate of HPV-related cervical lesions among women with SLE and conflicting results have been reported [1], [2]. Here, we conducted a systematic review of the literature and a meta-analysis to quantify the risk for high-grade squamous intraepithelial lesions (HSIL), the precancerous cervical lesions [5], [6] in patients with SLE compared to a healthy control population. We used the cytological criteria of HSIL, rather than the histological one of high grade cervical intraepithelial neoplasia, since cervical cancer screening is performed through cytological screening [7]. We believe that these data may provide useful guidance to clinicians and policymakers for implementing primary prevention through HPV vaccination and specific screening guidelines in women with SLE.
Section snippets
Methods
This meta-analysis was performed in accordance with the recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group [8].
Literature search
Our literature search identified 262 citations, of which 7 unique studies [9], [10], [12], [13], [14], [15], [16], [17] reported on HSIL were included in this meta-analysis (Fig. 1).
Publication bias
Visual examination of the funnel plots (Fig. 2) only revealed minor asymmetry.
Selected studies
The characteristics of the 7 studies included in the meta-analysis [9], [10], [12], [13], [14], [15], [16], [17] are shown in Table 1.
Included studies were 3 cross-sectional studies [9], [10], [16], [17], 2 case–control studies [12], [15],
Discussion
This systematic review of the literature provides the first summary of published evidence of the association between high grade cervical lesions and SLE. Combining the studies revealed a 9-fold increase in the risk of high grade cervical squamous intraepithelial lesions in SLE women, compared to healthy controls.
One mechanism that could account for the increased risk of HSIL is that SLE itself could induce defective clearance mechanisms toward HPV or HPV infected epithelial cells [3].
Take home messages
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Conflicting data have been published regarding the risk of precancerous cervical lesions among women with systemic lupus erythematosus (SLE).
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We systematically reviewed the evidence for an association between SLE and High-grade Squamous Intraepithelial lesions (HSIL).
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Our meta-analysis shows that the risk of HSIL is strongly increased in SLE patients versus female controls (OR: 8.66 [95%CI: 3.75–20.00]).
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Specific screening guidelines with shorter intervals between screenings should be considered
Acknowledgments
None
No author has any conflict of interest to disclose.
Funding: none.
Contributorship:
Emilie ZARD, Laurent ARNAUD, Alexis MATHIAN, and Isabelle HEARD design the research. Emilie ZARD, Laurent ARNAUD, Alexis MATHIAN, and Isabelle HEARD collected data. Laurent ARNAUD performed statistical analysis. Emilie ZARD, Laurent ARNAUD, Alexis MATHIAN, Isabelle HEARD, Zeina CHAKHTOURA, Philippe TOURAINE, and Zahir AMOURA interpreted data. Emilie ZARD, Laurent ARNAUD, Alexis MATHIAN, Isabelle HEARD, Zeina
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Emilie ZARD, Laurent ARNAUD & Alexis MATHIAN contributed equally to this work.