Abstract
The reported rates of HER2 positivity in cervical cancer (CC) range from 0% to 87%. The importance of HER2 as an actionable target in CC would depend on HER2 positivity prevalence. Our aim was to provide precise estimates of HER2 overexpression and amplification in CC, globally and by relevant subgroups. We conducted a PRISMA compliant meta-analytic systematic review. We searched Medline, EMBASE, Cochrane database, and grey literature for articles reporting the proportion of HER2 positivity in CC. Studies assessing HER2 status by immunohistochemistry or in situ hybridization in invasive disease were eligible. We performed descriptive analyses of all 65 included studies. Out of these, we selected 26 studies that used standardized American Society of Clinical Oncology / College of American Pathologists (ASCO/CAP) Guidelines compliant methodology. We conducted several meta-analyses of proportions to estimate the pooled prevalence of HER2 positivity and subgroup analyses using geographic region, histology, tumor stage, primary antibody brand, study size, and publication year as moderators. The estimated pooled prevalence of HER2 overexpression was 5.7% (CI 95%: 1.5% to 11.7%) I2 = 87% in ASCO/CAP compliant studies and 27.0%, (CI 95%: 19.9% to 34.8%) I2 = 96% in ASCO/CAP non-compliant ones, p < 0.001. The estimated pooled prevalence of HER2 amplification was 1.2% (CI 95%: 0.0% to 5.8%) I2 = 0% and 24.9% (CI 95%: 12.6% to 39.6%) I2 = 86%, respectively, p = 0.004. No other factor was significantly associated with HER2 positivity rates. Our results suggest that a small, but still meaningful proportion of CC is expected to be HER2-positive. High heterogeneity was the main limitation of the study. Variations in previously reported HER2 positivity rates are mainly related to methodological issues.
Highlights
IntroductionIn 2020, more than 340 000 deaths were attributed to CC worldwide
Cervical cancer (CC) is a significant global public health problem [1]
If a study used IHC for HER2 protein overexpression followed by a non-In Situ Hybridization (ISH) method for HER2 amplification assessment, only data on IHC were included in the review
Summary
In 2020, more than 340 000 deaths were attributed to CC worldwide. It is the fourth leading cause of cancer-related mortality in women overall and the second among those under the age of 50 [2]. Human Papilloma Virus (HPV) is the main etiological factor of cervical carcinogenesis. It produces DNA damage, centrosome abnormalities, epigenetic changes, and DNA methylation [3] {Gupta, 2019 #391}. Despite the development of effective methods of primary (prophylactic anti-HPV vaccines) and secondary (screening for premalignant cervical lesions) prevention, it has been estimated that in low-income countries, where the proportion of patients with advanced disease is high [4, 5], a substantial reduction of the CC burden may take several decades [1]. The standard treatments available for progressive, recurrent, and metastatic disease are limited, highlighting the need for new therapeutic options [6,7,8]
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