Scholarlink

Introduction <p>Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)—a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems—have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences.</p> Methods <p>HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher’s exact/χ<sup>2</sup> tests were applied appropriately with <i>p</i>-values adjusted for multiple comparisons (<i>p</i> &lt; 0.05).</p> Results <p>HPV positivity was most frequent in cervical carcinomas (70%, 1200/1716). Importantly, 6% (96/1620) of NENs from all tissues were positive for HPV16 or HPV18. Among HPV-positive NENs, 93% were high-grade compared to 54% observed in HPV-negative NENs (<i>p</i> &lt; 0.001), highlighting a strong association between HPV and tumor aggressiveness in this subset. Analysis of HPV-associated sites (cervix, anorectal region, and head and neck) revealed that HPV-positive NENs possess distinct genomic and transcriptomic landscapes compared to HPV-positive non-NENs. Notably, interferon signaling was significantly suppressed in HPV-positive NENs, suggesting a unique tumor-immune microenvironment.</p> Conclusions <p>Our findings indicate that HPV-positive NENs form a distinct subset with unique genomic features, including reduced interferon signaling, compared to HPV-positive non-NENs. Thus, future studies focused on evaluating HPV status, along with genomic and transcriptomic characteristics, may uncover biologically and clinically actionable distinctions for this rare yet clinically significant tumor subgroup.</p> Clinical trial number <p>Not applicable</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genomic and transcriptomic differences between neuroendocrine neoplasms and carcinomas with human papillomavirus (HPV)

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月2日

查看全文
  • Morgann Madill,
  • Udhayvir Grewal,
  • Harris Krause,
  • Andrew Elliott,
  • Marya Wahidi,
  • Janet S. Rader,
  • Deanna Teoh,
  • Soo J. Park,
  • John Wallbillich,
  • David J. Benjamin,
  • Arash Rezazadeh Kalebasty,
  • Penelope Duerksen-Hughes,
  • Robert Morris,
  • Radhika Gogoi,
  • Fadi Zaiem,
  • Thomas J. Herzog,
  • Premal H. Thaker,
  • Dave Bryant,
  • Matthew Oberley,
  • Heloisa Soares,
  • Joanne Xiu,
  • Andrew Hinton,
  • Deepti Jain,
  • Britt K. Erickson,
  • Martina Bazzaro,
  • Emil Lou,
  • Rouba Ali Fehmi

摘要

Introduction

Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)—a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems—have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences.

Methods

HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher’s exact/χ2 tests were applied appropriately with p-values adjusted for multiple comparisons (p < 0.05).

Results

HPV positivity was most frequent in cervical carcinomas (70%, 1200/1716). Importantly, 6% (96/1620) of NENs from all tissues were positive for HPV16 or HPV18. Among HPV-positive NENs, 93% were high-grade compared to 54% observed in HPV-negative NENs (p < 0.001), highlighting a strong association between HPV and tumor aggressiveness in this subset. Analysis of HPV-associated sites (cervix, anorectal region, and head and neck) revealed that HPV-positive NENs possess distinct genomic and transcriptomic landscapes compared to HPV-positive non-NENs. Notably, interferon signaling was significantly suppressed in HPV-positive NENs, suggesting a unique tumor-immune microenvironment.

Conclusions

Our findings indicate that HPV-positive NENs form a distinct subset with unique genomic features, including reduced interferon signaling, compared to HPV-positive non-NENs. Thus, future studies focused on evaluating HPV status, along with genomic and transcriptomic characteristics, may uncover biologically and clinically actionable distinctions for this rare yet clinically significant tumor subgroup.

Clinical trial number

Not applicable