HER2 expression in cervical squamous cell carcinoma - high prevalence of HER2-low/ultralow and spatiotemporal heterogeneity across tumor evolution

Sep 28, 2026

Uploaded by Ophelia

HER2 expression in cervical squamous cell carcinoma is investigated through evaluation of 548 untreated primary CSCC lesions comprising 313 biopsies and 235 hysterectomies. Initial immunohistochemistry (IHC) stratified cases into 0, 1+, 2+ (equivocal), and 3+ categories, and fluorescence in situ hybridization confirmed HER2 gene amplification in 3+ cases and a subset of 2+ cases. Reclassification yielded HER2-null, HER2-ultralow, HER2-low, and HER2-positive subgroups, with frequent discordance between paired specimens. Temporal and metastatic analyses quantify conversion rates over tumor evolution, supporting ADC therapy eligibility for low-expression subtypes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Background

HER2 as a therapeutic biomarker

Low-level HER2 and ADCs

Study Design and Methods

Patient cohort and lesion sampling

IHC and FISH assessment

Reclassification criteria

Results

HER2 prevalence and subtype distribution

Discordance across biopsies and hysterectomy

Temporal conversion and metastatic heterogeneity

Clinical Implications

Potential ADC eligibility in CSCC

npj | precision oncology Article | Published in partnership with The Hormel Institute, University of Minnesota | | | | --- | --- | --- | | [https://doi.org/10.1038/s41698-025-01189-w](https://doi.org/10.1038/s41698-025-01189-w) | | | | HER2 expression in cervical squamous cell carcinoma: high prevalence of HER2-low/ultralow and spatiotemporal heterogeneity across tumor evolution
Check for updates | | | | Wei Liu1,9, Xiaojiang Wang2,9, Yanmei Cui3,9, Keyi Song4, Weiqing Lin2, Xi Lei1, Xiuqin Weng1, Wucheng Shen1, Jingcheng Liu1, Libin Zhang5, Wenxiu Miao6, Juncheng Ye7, Tongmei He1, Qin Xu8 & Dan Hu1,4 | | | | Human epidermal growth factor receptor 2 (HER2) overexpression and gene ampliﬁcation are established biomarkers in breast and gastric cancers. However, their role in cervical squamous cell carcinoma (CSCC) remains unclear. We evaluated 548 untreated primary CSCC lesions (313 biopsies and 235 hysterectomies) . Initial immunohistochemistry (IHC) results were: 0 (56.9%), 1+ (26.3%), 2+(equivocal, 14.1%), and 3+ (positive, 2.7%) . Fluorescence in situ hybridization conﬁrmed HER2 gene ampliﬁcation in all 3+ cases and 5.2% of 2+ cases. Based on reclassiﬁcation, HER2 status was categorized as HER2-null (24.4%), HER2-ultralow (32.5%), HER2-low (39.6%), and HER2-positive (3.5%) . HER2 discordance rates were observed in 48.3% of paired biopsies and hysterectomy specimens, 52.2% of post-neoadjuvant residual lesions, and 50.8% of metastatic sites. Temporal analysis showed conversion rates of 50.0% for synchronous metastases, 30.8% within 12 months, and 63.6% beyond 12 months. We identiﬁed a high prevalence of HER2-low and HER2-ultralow subtypes, suggesting potential eligibility for ADC therapies. | | | | Cervical squamous cell carcinoma (CSCC) remains a leading cause of cancer-related morbidity and mortality among women globally, particularly in regions with limited access to screening and early intervention1. Despite preventive strategies, such as human papillomavirus(HPV)vaccination and cytological screening, the prognosis for patients with advanced or recurrent CSCC remains poor owing to the limited efﬁcacy of current treatments. Existing therapeutic options—including surgery, chemotherapy, and radiation therapy—often fail to effectively treat metastatic or recurrent disease, highlighting the need for novel, targeted therapies1.
Human epidermal growth factor receptor 2 (HER2), a member of the ErbB family ofreceptor tyrosine kinases, plays a critical role in regulating cell proliferation, survival, and differentiation2–4. The approval of HER2- | targeted monoclonal antibodies, such as trastuzumab and pertuzumab, marked a signiﬁcant advancement in treating HER2-positive breast cancer, thereby improving patient outcomes and establishing a foundation for targeted therapy. Encouraged by these successes, HER2-targeted monoclonal antibodies have demonstrated promising efﬁcacy in other solid tumors, including gastric, urothelial, and endometrial cancers5,6. This clinical success has sparked interest in investigating HER2asa therapeutic target in CSCC.
Antibody–drug conjugates (ADCs), combining HER2-targeting antibodies with potent cytotoxic payloads, have revitalized the therapeutic targeting of HER2 in cancers exhibiting low-level expression7. This resurgence is largely driven by the marked efﬁcacy demonstrated by ADCs, | | 1Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. 2Department of Molecular Pathology Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. 3Department of Pathology, People’s Hospital Afﬁliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China. 4The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China. 5Medical Records Room, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. 6Department of Pat

FAQs

What biomarkers and assays were used to assess HER2 in CSCC?

HER2 status was evaluated using initial immunohistochemistry (IHC), with fluorescence in situ hybridization (FISH) confirming HER2 gene amplification in selected cases.

How were CSCC lesions reclassified into HER2 subtypes?

Based on reclassification, lesions were categorized as HER2-null, HER2-ultralow, HER2-low, and HER2-positive, reflecting differences in IHC findings and confirmed amplification.

What did temporal and metastatic analyses show about HER2 status changes?

Temporal conversion rates differed by time window, and HER2 discordance was observed across paired biopsy and hysterectomy specimens as well as between residual and metastatic sites, indicating spatiotemporal heterogeneity.

Sep 28, 2026

Uploaded by Ophelia