777 Genomic Characterization of Human Papillomavirus (HPV)-Associated Carcinoma of the Bladder

Document Type

Conference Proceeding

Publication Date

3-23-2026

Publication Title

Lab Invest

Keywords

fibroblast growth factor receptor 3, aged, Alphapapillomavirus, anus carcinoma, bladder, bladder cancer, bladder carcinoma, carcinoma in situ, conference abstract, female, genetic profile, hematuria, high throughput sequencing, human, human tissue, immunohistochemistry, in situ hybridization, invasive carcinoma, keratinization, major clinical study, male, neurogenic bladder, oropharynx, papillomavirus infection, promoter region, squamous cell carcinoma, transitional cell carcinoma

Abstract

Disclosures: Merve Basar: None; Gamze Gokturk Ozcan: None; Cansu Yol: None; Dilara Akbulut: None; Jie-Fu Chen: None; Bin Xu: None; Judy Sarungbam: None; Ying-Bei Chen: None; Anuradha Gopalan: None; Samson Fine: None; Satish Tickoo: None; Victor Reuter: None; Gopa Iyer: None; Chad Vanderbilt: None; Hikmat Al-Ahmadie: None Background: The association between HPV infection and squamous cell carcinomas (SCC) of the uterine cervix and oropharynx is well established and widely studied. Although HPV-associated carcinomas of the bladder (HPV-BC) have been reported, these tumors are rare, and their exact molecular features have not been established. Design: We identified 20 HPV-BC cases and analyzed their clinicopathologic features. In situ hybridization (ISH) for high-risk HPV and immunohistochemistry for p16 stain were performed. Targeted Next Generation Sequencing (NGS) was performed on 12 tumors with available tissue. For comparison, cervical (n=221), head and neck (n=140), and anal (n=127) carcinomas were also analyzed. NGS explored the presence of HPV DNA in the tumors. We also included 71 cases of urothelial carcinoma with squamous differentiation (UC-SDQ) for comparison of genomic characterization. Results: There were 16 female (80%) and 4 male (20%) patients. The age range was 43-82 years (mean 63.9; median 66). The most common presenting symptom was gross hematuria (65%), followed by urgency, frequency and incomplete emptying. Self-catheterization due to neurogenic bladder or obstructive symptoms was reported in 6 patients (30%). Invasive carcinoma was present in 15 cases whereas in 5 cases only non-invasive carcinoma was present. All cases showed variable levels of squamous differentiation, the majority of which being of basaloid morphology (n=16, 80%) with or without keratinization. HR HPV-ISH was positive in all cases and p16 was positive in 10 (50%). In 12 tumors with available NGS data (Figure 1), the most common alterations include: TERT amplification, FGFR3 mutation, PIK3CA mutation/amplification, TP53 mutation/deletion, TP63 amplification & KMT2D mutation (n=4, 33%, each). One HPV-associated bladder cancer harbored TERT promoter mutation that also had TERT amplification, compared to 70% of UC-SQD. No TP63 amplification was identified in UC-SQD. Notable recurrent chromosomal arm gain /loss in HPV-BC include 3q gain and 11q loss in 7 tumors (60%), which was similar to HPV associated cervical, head and neck and anal carcinoma but not in urothelial carcinoma. [Formula presented] Conclusions: HPV-BC is rare, more common in women and exhibits predominant basaloid morphology. The genomic profile of HPV-BC is heterogeneous and shares features with HPV-associated carcinomas in other organs. Recurrent alterations that can help in distinguishing HPV-BC from UC-SQD include amplification of TP63 and TERT, 3q gain and loss of 11q.

Volume

106

Issue

3

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