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MEH mainly affects children and adolescents in Indigenous American populations, though reports now extend to nonendemic regions, with typical cobblestone-like papules or nodules and characteristic histology.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/multifocal-epithelial-hyperplasia-clinical-features-diagnosis-and-management-challenges/435116/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/multifocal-epithelial-hyperplasia-clinical-features-diagnosis-and-management-challenges/435116.png","ImageObject",300,407,{"name":42,"@type":43},"Aldword","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is multifocal epithelial hyperplasia (MEH)?","Question",{"text":63,"@type":64},"MEH, also called Heck’s disease, is a rare and benign proliferation of the oral mucosa. It is strongly linked to low-risk HPV genotypes 13 and 32.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does MEH typically present clinically and histologically?",{"text":68,"@type":64},"MEH usually presents as multiple, asymptomatic papules or nodules with a cobblestone-like appearance. Histology shows epithelial hyperplasia, koilocytosis, and altered cytokeratin expression.",{"name":70,"@type":61,"acceptedAnswer":71},"What diagnostic methods are highlighted for MEH?",{"text":72,"@type":64},"Molecular techniques such as polymerase chain reaction and in situ hybridization are emphasized for viral genotyping. Immunohistochemical markers including CK4/13, Ki-67, and absence of p16 can support differential diagnosis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},435116,1791308208,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","| W | J | E | M | World Journal of\u003Cbr>Experimental Medicine |\n| --- | --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Exp Med 2025 December 20; 15(4): 114368  \nDOI: 10.5493/wjem.v15.i4.114368 ISSN 2220-315x (online)  \nMINIREVIEWS  \nMultifocal epithelial hyperplasia: Clinical features, diagnosis and management challenges  \nCesar Omar Ramos-Gregorio, Omar Tremillo-Maldonado, Felipe Silveira, Lauren Frenzel Schuch, Vanesa Pereira-Prado, Estefania Sicco, Ana Cristina Soto-Najera, Marcelo GómezPalacio-Gastélum, Mario IsiordiaEspinoza, Juan José Muñoz-Ibarra, Victor Toral-Rizo, Ronell Bologna-Molina  \nSpecialty type: Medicine, research and experimental  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B  \nNovelty: Grade B  \nCreativity or Innovation: Grade B  \nScientific Significance: Grade A  \nP-Reviewer: Omullo FP, MD, Senior Researcher, Kenya  \nReceived: September 17, 2025  \nRevised: October 3, 2025  \nAccepted: December 4, 2025  \nPublished online: December 20, 2025  \nProcessing time: 93 Days and 14.9 Hours  \nCesar Omar Ramos-Gregorio, Omar Tremillo-Maldonado, Marcelo GómezPalacio-Gastélum, Ronell Bologna-Molina, Master Degree Program, Faculty of Dentistry, Universidad Juarez del Estado de Durango, Durango 34070, Mexico  \nFelipe Silveira, Lauren Frenzel Schuch, Vanesa Pereira-Prado, Estefania Sicco, Ana Cristina SotoNajera, Ronell Bologna-Molina, Department of Diagnostic in Oral Pathology and Oral Medicine, Faculty of Dentistry, Universidad de la República, Montevideo 11400, Uruguay  \nMario Isiordia-Espinoza, División de Ciencias Biomédicas, Universidad de Guadalajara Centro Universitario de los Altos, Tepetitlan de Morelos 47620, Jalisco, Mexico  \nJuan José Muñoz-Ibarra, Faculty of Dentistry, Universidad Anáhuac Mayab, Merida 93308, Yucatán, Mexico  \nVictor Toral-Rizo, Faculty of Dentistry, University of the Mexico State, Toluca 50130, Mexico  \nCorresponding author: Ronell Bologna-Molina, PhD, Professor, Department of Diagnostics in Oral Pathology and Oral Medicine, Faculty of Dentistry, University of the Republic, General Las Heras 1925, Montevideo 11600, [Uruguay.](Uruguay. ronellbologna@hotmail.com)[ ronellbologna@hotmail.com](Uruguay. ronellbologna@hotmail.com)  \nAbstract  \nMultifocal epithelial hyperplasia (MEH), also known as Heck’s disease, is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus (HPV) genotypes 13 and 32. This narrative review synthesizes recent findings regarding the epidemiology, viral mechanisms, clinical and histopathological features, diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH. This disease predominantly affects children and adolescents from Indigenous American countries, although cases have been increasingly reported in nonendemic regions. MEH manifests clinically as multiple, asymptomatic papules or nodules, typically exhibiting a characteristic cobblestone-like appearance. Histologically, it presents with epithelial hyperplasia, koilocytosis, and altered cytokeratin expression. Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping, while immunohistochemical markers such as CK4/13, Ki-67, and the absence of p16 can be useful adjuncts in differential diagnosis. Despite its self-limiting nature in most cases, treatment may be  \n WJEM  [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 20, 2025  Volume 15  Issue 4   \nRamos-Gregorio CO et al. Multifocal epithelial hyperplasia  \nwarranted in symptomatic or immunocompromised patients. This review highlights the need to improve diagnostic access, develop targeted vaccines, and implement public health strategies in vulnerable communities. It also highlights existing gaps in k","cbCaiqLHuaT0D4ph","https://ap.wps.com/l/cbCaiqLHuaT0D4ph","pdf",7215629,15,"English","# Abstract\n## Clinical features and histopathology\n## Etiology and viral mechanisms\n## Diagnosis: molecular and immunohistochemical methods\n## Management and therapeutic approaches\n## Public health implications and research gaps","[{\"question\":\"What is multifocal epithelial hyperplasia (MEH)?\",\"answer\":\"MEH, also called Heck’s disease, is a rare and benign proliferation of the oral mucosa. It is strongly linked to low-risk HPV genotypes 13 and 32.\"},{\"question\":\"How does MEH typically present clinically and histologically?\",\"answer\":\"MEH usually presents as multiple, asymptomatic papules or nodules with a cobblestone-like appearance. Histology shows epithelial hyperplasia, koilocytosis, and altered cytokeratin expression.\"},{\"question\":\"What diagnostic methods are highlighted for MEH?\",\"answer\":\"Molecular techniques such as polymerase chain reaction and in situ hybridization are emphasized for viral genotyping. Immunohistochemical markers including CK4/13, Ki-67, and absence of p16 can support differential diagnosis.\"}]","Multifocal epithelial hyperplasia - Clinical features, diagnosis and management challenges | PDF",1790672011,38]