Abstract
Cervical Cancer (CC) is a significantly prevalent disease in developing countries. Currently, targeted therapies are not a primary standard of care in CC. This information could be crucial for developing directed therapies and patient screening for biomarkers that would allow personalised treatment of CC. This systematic review aimed to estimate the prevalence of potential therapeutic targets such as the epidermal growth factor receptor (EGFR) and the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways in patients with CC, identified through genomic and non-genomic testing. Studies were identified through an ad-hoc search strategy from the available on MEDLINE (Ovid), CENTRAL, LILACS, SCOPUS, through the Clinical Trial registry on Clinicaltrials.gov, International Clinical Trials Registry Platform, RENIS (Argentine National Registry of Health Research) and grey literature sources. We included 74 studies which represented a total pool of 7,862 participants. Forty-five studies informed mutations of EGFR, with a combined positivity rate of 53% (95%CI: 45%–60%; I2 = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%–39%; I2 = 96%). Twenty-three studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%–21%; I2 = 95%). Raf mutations were informed in six studies. Six studies informed the presence of Akt mutations, two studies informed mTOR mutations and only one study reported mutations of MAPK. The most frequently described therapeutic targets were EGFR, and the PIK3CA and Ras pathways, though inconsistency in positivity rates was significant. Our study did not allow the identification of any specific clinical characteristics that might explain the observed heterogeneity. Despite the overall good quality of the included studies, the applicability of these results to patients’ general population with CC is still unclear.
Highlights
Cervical-uterine cancer is the second most diagnosed cancer in women in developing countries
We considered the following markers: epidermal growth factor receptor (EGFR), and both phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR and Ras/Raf/MAPK intracellular pathways
After the initial title and abstract screening process of all the initially recovered articles, 167 studies were selected for full-text review
Summary
Cervical-uterine cancer is the second most diagnosed cancer in women in developing countries. In 2018, 570,000 women were diagnosed with cervical cancer (CC), and 311,000 died from this cause, constituting the fourth in frequency among women and the fourth as a cause of death. 84% of all CCs and 88% of all deaths caused by this cancer occurred in lower resource countries [1,2,3]. Infection by human papillomavirus (HPV) has been clearly established as a necessary cofactor for the development of CC. The use of cervical cytology, known as Papanicolaou testing, as well the addition of HPV co-testing has significantly improved the detection and treatment of precursor and preinvasive cervical lesions, allowing to identify patients who are at greater risk of developing CC [1]
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