{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:17:01Z","timestamp":1791231421048,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Vulvar cancer is a rare gynecologic malignancy comprising 1\u20133% of all cases. No established standard exists for advanced disease, and treatment is often extrapolated from cervical cancer. Although HER2 overexpression is well defined in breast cancer and recognized across multiple solid tumors, its prevalence and significance in vulvar cancer remain unclear. Recent activity of HER2-directed antibody\u2013drug conjugate Trastuzumab deruxtecan in solid tumors with an objective response rate (ORR) of around 37% highlights the need to better characterize HER2 expression in vulvar cancer. Methods: We performed a systematic search of Medline, Embase, and the Cochrane Library up to May 2025. Eligible studies included \u226510 vulvar cancer cases, predominantly vulvar squamous cell carcinoma (VSCC), excluding vulvar Paget\u2019s disease, with available HER2 assessment by immunohistochemistry and\/or in situ hybridization. Two reviewers independently screened the studies. A random-effects model was used to estimate pooled HER2 positivity. Heterogeneity was assessed using Cochrane\u2019s Q and Higgins\u2019s I2. Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n = 752) met inclusion criteria. A total of 50 HER2-positive cases were observed. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Molecular profiling was limited. Among three studies with known TP53 status (n = 206), 59% of the tumors expressed TP53 (n = 122), and among two studies with known human papilloma virus (HPV) status (n = 128), 21% (n = 27) were HPV-positive. Six studies used American Society of Clinical Oncology\/College of American Pathologists (ASCO\/CAP) HER2 testing guidelines in breast cancer. Pooled HER2-positive expression across ASCO\/CAP-based studies was 2% (95% CI: 1%, 3%) and for non-ASCO\/CAP-based studies was 21% (95% CI: 2%, 52%). Exploratory pooled estimated proportion of HER2-positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies, I2 value of 91.1% [95% CI: 85.4%; 94.6%], and no significant publication bias was observed (Egger\u2019s test p = 0.364). This study could not assess prognostic value of HER2 overexpression in VSCC. Conclusions: HER2 positivity in VSCC appears uncommon but it remains to be fully explored. Standardized assessment using contemporary ASCO\/CAP breast, endometrial-specific and\/or gastric criteria are needed to clarify the prevalence of HER2-positive versus HER2-low\/ultralow disease to inform potential use of HER2-targeted therapy.<\/jats:p>","DOI":"10.3390\/cancers18132162","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:43:11Z","timestamp":1783334591000},"page":"2162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HER2 Expression in Squamous Cell Carcinoma of the Vulva: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Natalia Luisy","family":"Farias M\u00fcller","sequence":"first","affiliation":[{"name":"School of Medicine, University of Southern Santa Catarina (UNISUL), Palhoca 88137-270, Santa Catarina, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maitha Al","family":"Sibani","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Kareem","family":"Pullattayil","sequence":"additional","affiliation":[{"name":"Health Sciences Library, Queen\u2019s University, Kingston, ON K7M 5R7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farideh","family":"Tavangar","sequence":"additional","affiliation":[{"name":"Lawrence Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON M5T 1P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9216-8500","authenticated-orcid":false,"given":"Anna","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Lakeridge Health, Oshawa, ON L1G 2B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-1883","authenticated-orcid":false,"given":"Sophia","family":"George","sequence":"additional","affiliation":[{"name":"Division of Gynecology Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Miller School of Medicine, University of Miami, Miami, FL 33146, USA"},{"name":"Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna J.","family":"Jerzak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Chehade","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ijgo.12609","article-title":"Cancer of the vulva","volume":"143","author":"Rogers","year":"2018","journal-title":"Int. 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