HER2 Expression and Its Correlation With Clinicopathological Features and Prognosis in Extramammary Paget's Disease: A Systematic Review and Meta-Analysis

Background: Extramammary Paget's disease (EMPD) is a neoplastic condition primarily in the anogenital region. A subset of cases exhibits HER2 expression, generally associated with poor prognosis. This paper aimed to systematically explore the potential correlation between HER2 expression, clinicopathological features and prognosis in EMPD. Methods: A systematic search (1990–2023) was conducted via BVS, Embase, Google Scholar, PubMed, Scopus and Web of Science. A meta-analysis with odds ratios (ORs) and confidence intervals (CIs) was performed. Results: A total of 954 patients from 16 studies were included. The median age at diagnosis was 70.3 years, with the majority being men (71.8%). The penoscrotal area was the most common site of presentation. HER2 positivity was 25.6%, and the HER2-low proportion was 38.5%. Positive HER2 expression was correlated with EMPD dermal invasion (OR = 4.01, 95% CI: 2.11–7.62) and the presence of lymph node metastasis (OR = 3.84, 95% CI: 1.59–9.30), but not with the presence of secondary malignancies or the female gender. Gene expression among patients with IHC 2+ and 3+ was correlated with tumour dermal invasion (pooled OR = 6.43, 95% CI: 1.23–33.57). No correlation was found between HER2-low expression and dermal invasion, lymph node metastasis or the presence of secondary primary malignancies. Conclusion: HER2 was expressed in a significant proportion in EMPD with significant correlations, suggesting its potential role as a prognostic biomarker.