Differences in genomic and transcriptomic landscapes of human papillomavirus (HPV)–positive neuroendocrine neoplasms and HPV-positive carcinoma.

• DOI: 10.1200/jco.2024.42.16_suppl.4127
• Publication Date: 2024-06-21T18:10:11Z
• Authors: Emil Lou; Harris Benjamin K...; Andrew Elliott; Marya Wahidi; Janet S. Rader; Deanna Gek Koon Teoh; Soo J Park; John Wallbillich; David Joseph Benj...; Arash Rezazadeh; Penelope Duerksen...; Robert Morris; Radhika Gogoi; Fadi Zaiem; Thomas J Herzog; Premal H. Thaker; Matthew James Obe...; Heloisa P. Soares; Rouba Ali-Fehmi
• Keywords: Neuroendocrine carcinoma

4127 Background: HPV is an infectious cause of several malignancies. Neuroendocrine neoplasms (NEN) are highly heterogeneous, ranging from low-grade indolent tumors to high-grade clinically aggressive carcinomas. Aside cervical NENs, most have not traditionally been associated with HPV, but our initial studies uncovered a subset NENs that 16/18 positive. To identify actionable differences between HPV+ NEN and non-NENs, genomic transcriptomic landscapes were investigated. Methods: 101343 solid sequenced at Caris Life Sciences (Phoenix, AZ) NextGen Sequencing DNA (whole or hybrid exome) RNA transcriptome) assayed for HPV16/18 positivity (HPV+) via sequencing. Mutation prevalence pathogenic SNVs/indels (-Mt) copy number amplification (CNA) calculated. Expression Ki-67 mRNA ( MKI67) was used infer high grade vs low NEN. Gene expression profiles analyzed transcriptional signature predictive response immunotherapy, interferon 𝛾">γ score (IFN). Differentially regulated pathways assessed by gene set enrichment analysis (GSEA). Fisher’s exact/χ2 tests applied as appropriate p-values adjusted multiple comparisons p < .05). Results: Among all tumor types, rates highest in carcinomas (70%, 1200/1716), followed vulvar squamous cell carcinoma (31%, 126/410) head neck (HN) (28%, 668/2413), also found (6%, 96/1620). Within the observed those origin (76%, 55/58), anorectal (AR, 27%, 29/106), female genitourinary tract (23%, 12/52) HN (19%, 7/36). Amongst NEN, 93% compared 54% HPV- (p .001). Focusing on AR, primary sites, significant landscape non-NEN v (Table 1). Non-NEN had significantly higher IFN across sites (Cervical: -0.20 -0.61, AR: -0.33 -0.58, HN: -0.16 -0.54 arbitrary units, .001 all). enriched genes sets related immune (Interferon α/γ, TNFα/NF-κβ, IL6/JAK/STAT3 inflammatory response). Conclusions: Our data suggest immunotherapy response, alterations vary anatomic site. We uncover category distinct tumors. [Table: see text]