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Meta-Analysis
. 2021 Sep 30;16(9):e0257976.
doi: 10.1371/journal.pone.0257976. eCollection 2021.

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

Boris Itkin  1 , Agustin Garcia  2 , Samanta Straminsky  1 , Eduardo Daniel Adelchanow  3 , Matias Pereyra  4 , Gabriela Acosta Haab  5 , Ariel Bardach  6
Affiliations
Meta-Analysis

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

Boris Itkin et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA diagram of the study selection process.
Fig 2
Fig 2. Subgroups of studies according to the methods used for HER2 positivity determination.
Abbreviations: IHC = Immunohistochemistry, ISH = In Situ Hybridization.
Fig 3
Fig 3. Prevalence of HER2 overexpression according to ASCO/CAP-compliant guidelines.
Abbreviations: ASCO = American Society of Clinical Oncology, CAP = College of American Pathologists, DL = Der Simonian and Laird, ME = mixed effects.
Fig 4
Fig 4. Subgroup analysis by histologic subtype.
All studies. Abbreviations: DL = Der Simonian and Laird, ME = mixed effects.
Fig 5
Fig 5. Studies that included both squamous and non-squamous histology.
Abbreviations: DL = Der Simonian and Laird, ME = mixed effects.
Fig 6
Fig 6. Subgroup analysis by World Health Organization geographic region.
Abbreviations: DL = Der Simonian and Laird, ME = mixed effects.
Fig 7
Fig 7. Subgroup analysis by primary antibody brand.
Abbreviations: DL = Der Simonian and Laird, ME = mixed effects.
Fig 8
Fig 8. Relationship between the year of study publication, size, and HER2 overexpression prevalence.
Fig 9
Fig 9. Prevalence of HER2 amplification according to compliance with ASCO/CAP guidelines.
Abbreviations: ASCO = American Society of Clinical Oncology, CAP = College of American Pathologists, DL = Der Simonian and Laird, ME = mixed effects.
Fig 10
Fig 10. HER2 overexpression prevalence in selected histologic subtypes.
Abbreviations: DL = Der Simonian and Laird, ME = mixed effects.
See this image and copyright information in PMC

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