Prevalence of HER2 overexpression and amplification in cervical cancer: A systematic review and meta-analysis

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.

Pattern A endocervical adenocarcinomas with ovarian metastasis are indolent and molecularly distinct from destructively invasive adenocarcinomas

“…This confirms similar observations recently made in a larger cohort of HPVA not restricted to cases with metastatic disease 10 . In concordance with prior studies, we also identified two patients in group 2 with tumours showing ERBB2 amplification, highlighting the value of evaluating for this targetable genetic alteration in cervical adenocarcinomas when clinically indicated 32 …”

“…10 In concordance with prior studies, we also identified two patients in group 2 with tumours showing ERBB2 amplification, highlighting the value of evaluating for this targetable genetic alteration in cervical adenocarcinomas when clinically indicated. 32 From a clinical outcome perspective, patients with pattern A HPVA/AIS and ovarian involvement in our cohort did well: all were free of disease with median follow-up of 53 months. This contrasts with the adverse outcome frequently seen in patients with pattern B/C HPVA and metastatic disease.…”

Recurrent or primary metastatic cervical cancer: current and future treatments

“… 31 , 32 , 33 Furthermore, human EGFR2 (HER2) mutations and amplifications were observed in 3%-6% and 1%-12% of CC, respectively, and were also correlated with a worse prognosis. 34 Although EGFR inhibition seemed a promising target in CC treatment, several phase II studies evaluating EGFR inhibitors such as cetuximab, gefitinib, erlotinib, or lapatinib showed only limited activity. 27 , 35 , 36 , 37 Neratinib was explored in the phase II SUMMIT trial including 16 patients (62.5% of ADK) with HER2-mutated recurrent CC progressing after platinum-based treatment.…”

Comprehensive genomic and immunohistochemical profiles and outcomes of immunotherapy in patients with recurrent or advanced cervical cancer

“…Furthermore, our study showed that HER2 was not expressed in patients with squamous cell histology, whereas HER2 2+ and 3+ were identified in patients with non-squamous histology. Previous studies have indicated that a small, yet meaningful, proportion of patients with cervical cancer overexpress the HER2 receptor ( 19 , 20 ). In our study, two patients overexpressing HER2 received T-DXd and showed a good response considering the treatment setting.…”