Patrono Maria Guadalupe, Calvo Maria Florencia, Franco Juan Victor Ariel, Garrote Virginia, Vietto Valeria
Department of Gynecology, Hospital Italiano de Buenos Aires, Gascon 450, Buenos Aires C1181ACH, Argentina.
https://orcid.org/0000-0002-1309-2114.
Ecancermedicalscience. 2021 Mar 9;15:1200. doi: 10.3332/ecancer.2021.1200. eCollection 2021.
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%; I = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%-39%; I = 96%). Twenty-three studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%-21%; I = 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.
宫颈癌（CC）在发展中国家是一种相当普遍的疾病。目前，靶向治疗并非CC的主要治疗标准。这些信息对于开发定向治疗以及针对生物标志物进行患者筛查从而实现CC的个性化治疗可能至关重要。本系统评价旨在评估通过基因组和非基因组检测确定的CC患者中潜在治疗靶点的患病率，如表皮生长因子受体（EGFR）以及PI3K/Akt/mTOR和Ras/Raf/MAPK通路。通过专门的检索策略，从MEDLINE（Ovid）、CENTRAL、LILACS、SCOPUS上的可用文献、Clinicaltrials.gov上的临床试验注册库、国际临床试验注册平台、RENIS（阿根廷国家卫生研究注册库）以及灰色文献来源中检索相关研究。我们纳入了74项研究，这些研究共涉及7862名参与者。45项研究报告了EGFR突变，合并阳性率为53%（95%CI：45%-60%；I² = 95%）。20项研究报告了PIK3CA突变的存在，合并阳性率为30%（95%CI：21%-39%；I² = 96%）。23项研究报告了Ras突变，合并阳性率为14%（95%CI：8%-21%；I² = 95%）。6项研究报告了Raf突变。6项研究报告了Akt突变的存在，2项研究报告了mTOR突变，仅有1项研究报告了MAPK突变。最常描述的治疗靶点是EGFR以及PI3KCA和Ras通路，尽管阳性率存在显著的不一致性。我们的研究未能确定任何可能解释所观察到的异质性的特定临床特征。尽管纳入研究的总体质量良好，但这些结果对CC患者总体人群的适用性仍不明确。
