{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:22:19Z","timestamp":1790792539587,"version":"4.1.0"},"reference-count":31,"publisher":"Societatea Romana de Morfologie","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rom J Morphol Embryol"],"published-print":{"date-parts":[[2025,12,12]]},"abstract":"<jats:p>Human papillomavirus (HPV) is a well-established etiological agent for cervical cancer, yet its contribution to endometrial malignancies remains underrecognized and mechanistically distinct. This paper synthesizes current evidence to explain the delayed onset of HPV-associated endometrial tumors compared with cervical cancer, organizing the discussion into seven pathogenetic factors. Anatomical distance and the barrier function of the cervical canal and mucus reduce direct viral access to the endometrium. Cyclical shedding of the functional layer imposes a \u201creset\u201d that hinders long-term viral persistence, in contrast to the relatively stable cervical epithelium. Prolonged viral latency in the endometrium, combined with a lower frequency of reactivation, further extends the carcinogenic timeline. We highlight the necessity of additional, non-HPV-driven genetic alterations, particularly involving phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and mismatch repair (MMR) defects, on which HPV oncoproteins E6\/E7 may act as late-stage accelerants rather than primary initiators. Hormonal factors, especially prolonged unopposed estrogen exposure and progesterone-driven immune tolerance, modulate both tissue susceptibility and viral persistence. The endometrial immune microenvironment, adapted for reproductive tolerance, provides cyclical windows of reduced antiviral surveillance that HPV can exploit, while co-infections and microbial dysbiosis facilitate viral ascent, chronic inflammation, and genomic instability. These concepts are illustrated by a case of a woman with prior HPV-induced cervical squamous cell carcinoma who, a decade later, developed a vulvar condyloma and an endometrial stromal sarcoma with a mesenchymal immunophenotype [desmin, cluster of differentiation 10 (CD10), and caldesmon positivity]. The case underscores the possibility of long-latency, field effects, and divergent histological outcomes following HPV exposure. We also discuss emerging data suggesting that endometriosis and other ectopic endometrial proliferations may act as viral reservoirs. Overall, HPV appears to function as a co-factor within a multifactorial pathogenetic network, contributing to a subset of endometrial malignancies after a protracted, decades-long carcinogenic course.<\/jats:p>","DOI":"10.47162\/rjme.66.3.02","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:41:45Z","timestamp":1768819305000},"page":"443-451","source":"Crossref","is-referenced-by-count":1,"title":["Delayed onset of HPV-associated uterine malignancies: seven pathogenetic factors in contrast to cervical cancer"],"prefix":"10.47162","volume":"66","author":[{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania; Department of Obstetrics and Gynecology, Philanthropy Municipal Clinical Hospital, Craiova, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda Lorena","family":"Dijm\u0103rescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana-Victoria","family":"Camen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania; Department of Obstetrics and Gynecology, Philanthropy Municipal Clinical Hospital, Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Magdalena","family":"Manolea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania; Department of Obstetrics and Gynecology, Philanthropy Municipal Clinical Hospital, Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Radu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Family Medicine, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Anghelina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pediatrics, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Boldea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra-Daniela","family":"Rotaru-Z\u0103v\u0103leanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Epidemiology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mircea-Sebastian","family":"\u015eerb\u0103nescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, Romania; Department of Pathology, Philanthropy Municipal Clinical Hospital, Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"26736","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"\"[1] Jain M, Yadav D, Jarouliya U, Chavda V, Yadav AK, Chaurasia B, Song M. 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