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Although HPV has recently been implicated in a small subset of adenocarcinomas and small-cell neuroendocrine carcinomas of the anorectum, its involvement in both components of a gastrointestinal mixed neuroendocrine\u2013nonneuroendocrine neoplasm (MiNEN) has not been previously described. We herein report a novel tumor, an HPV-associated MiNEN of the rectum in a 60-year-old woman. The patient presented for colonoscopy screening, during which a distal rectal polyp was identified and excised. Histologic examination of the resected tumor demonstrated two intimately admixed components, an adenocarcinoma and a small-cell neuroendocrine carcinoma. Both components showed strong and diffuse p16 immunoreactivity, and high-risk HPV RNA in situ hybridization demonstrated transcriptionally active HPV in both tumor populations, confirming HPV as a likely shared oncogenic driver. To our knowledge, this represents the first well-documented HPV-associated MiNEN in the gastrointestinal tract.<\/jats:p>","DOI":"10.1177\/10668969251414864","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T01:08:09Z","timestamp":1771808889000},"page":"1290-1294","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel HPV-associated Mixed Neuroendocrine\u2013Nonneuroendocrine Neoplasm of the Rectum"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0043-9189","authenticated-orcid":false,"given":"Ari","family":"Kassardjian","sequence":"first","affiliation":[{"name":"Southern California Permanente Medical Group, Woodland Hills Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafis","family":"Shafizadeh","sequence":"additional","affiliation":[{"name":"Southern California Permanente Medical Group, Woodland Hills Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Shi","sequence":"additional","affiliation":[{"name":"Southern California Permanente Medical Group, Woodland Hills Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"e_1_3_2_2_2","volume-title":"WHO Classification of Tumours of Endocrine Organs","author":"Lloyd RV","year":"2017","unstructured":"Lloyd RV, Osamura RY, Kl\u00f6ppel G, Rosai J, eds. 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