{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:21:09Z","timestamp":1789651269752,"version":"4.0.0"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Perianal fistulizing Crohn\u2019s disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn\u2019s disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn\u2019s disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn\u2019s disease. The incidence rate of SCC related to perianal fistula was very low (&lt;1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron\u2019s disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer.<\/jats:p>","DOI":"10.3390\/cancers13061445","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:13:26Z","timestamp":1616411606000},"page":"1445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Fistula-Related Cancer in Crohn\u2019s Disease: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1591-1320","authenticated-orcid":false,"given":"Andromachi","family":"Kotsafti","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7055-635X","authenticated-orcid":false,"given":"Melania","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-5833","authenticated-orcid":false,"given":"Imerio","family":"Angriman","sequence":"additional","affiliation":[{"name":"First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"Castagliuolo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine DMM, University of Padua, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Caruso","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, ULSS2 Marca Trevigiana, Montebelluna Hospital, 31044 Montebelluna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/jcag\/gwy047","article-title":"Clinical Practice Guideline for the Medical Management of Perianal Fistulizing Crohn\u2019s Disease: The Toronto Consensus","volume":"1","author":"Steinhart","year":"2018","journal-title":"J. Can. Assoc. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1053\/gast.2002.32362","article-title":"The natural history of fistulizing Crohn\u2019s disease in Olmsted County, Minnesota","volume":"122","author":"Schwartz","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Scharl, M., Rogler, G., and Biedermann, L. (2017). Fistulizing Crohn\u2019s Disease. Clin. Transl. Gastroenterol., 8.","DOI":"10.1038\/ctg.2017.33"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nrgastro.2017.104","article-title":"Perianal fistulizing Crohn\u2019s disease: Pathogenesis, diagnosis and therapy","volume":"14","author":"Rimola","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1055\/s-2002-33417","article-title":"Das karzinom beim m. Crohn","volume":"40","author":"Winkler","year":"2002","journal-title":"Zeitschrift f\u00fcr Gastroenterologie"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.cgh.2017.11.041","article-title":"High Risk of Anal and Rectal Cancer in Patients With Anal and\/or Perianal Crohn\u2019s Disease","volume":"16","author":"Beaugerie","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/j.1365-2230.2005.01884.x","article-title":"Perineal squamous cell cancer in a patient with fistulizing and ulcerating Crohn\u2019s disease","volume":"30","author":"Fox","year":"2005","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/ecco-jcc\/jjv141","article-title":"European evidence-based consensus: Inflammatory bowel disease and malignancies","volume":"9","author":"Annese","year":"2015","journal-title":"J. Crohns Colitis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ijsu.2010.02.007","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"8","author":"Moher","year":"2010","journal-title":"Int. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1097\/DCR.0000000000000700","article-title":"Fistula-Associated Anorectal Cancer in the Setting of Crohn\u2019s Disease","volume":"59","author":"Shwaartz","year":"2016","journal-title":"Dis. Colon Rectum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1007\/BF02236948","article-title":"Carcinoma arising in anorectal fistulas of Crohn\u2019s disease (4) (multiple letters)","volume":"42","author":"Kulaylat","year":"1999","journal-title":"Dis. Colon Rectum"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1136\/gut.25.10.1124","article-title":"Malignant transformation of anal skin tags in Crohn\u2019s disease","volume":"25","author":"Somerville","year":"1984","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/gut.35.3.347","article-title":"Lower gastrointestinal malignancy in Crohn\u2019s disease","volume":"35","author":"Connell","year":"1994","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e232","DOI":"10.1016\/j.crohns.2012.09.015","article-title":"Squamous cell carcinoma associated anal fistulas in Crohn\u2019s disease unique case report with literature review","volume":"7","author":"Benjelloun","year":"2013","journal-title":"J. Crohns Colitis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1097\/00007611-199709000-00016","article-title":"Squamous cell carcinoma arising in an unhealed wound in Crohn\u2019s disease","volume":"90","author":"Sarani","year":"1997","journal-title":"South. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00384-009-0778-z","article-title":"Squamous cell carcinoma of the anus in a patient with perianal Crohn\u2019s disease","volume":"25","author":"Kang","year":"2010","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/DCR.0b013e318197d0ad","article-title":"Cancer of the anus complicating perianal Crohn\u2019s disease","volume":"52","author":"Devon","year":"2009","journal-title":"Dis. Colon Rectum"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00384-017-2794-8","article-title":"Long-standing Crohn\u2019s disease and its implication on anal squamous cell cancer management","volume":"32","author":"Lightner","year":"2017","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ehrl, D., Rentsch, M., Moellhoff, N., and Wachtel, N. (2020). Complex microsurgical perineal reconstruction after resection of a giant verrucous carcinoma associated with anal fistulas in Crohn\u2019s disease\u2014A unique case report. Int. J. Colorectal Dis.","DOI":"10.1007\/s00384-020-03569-z"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1007\/BF02237388","article-title":"Carcinoma arising in anorectal fistulas of Crohn\u2019s disease","volume":"41","author":"Ky","year":"1998","journal-title":"Dis. Colon Rectum"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF02560444","article-title":"The relationship between fistulas in Crohn\u2019s disease and associated carcinoma\u2014Report of four cases and review of the literature","volume":"28","author":"Church","year":"1985","journal-title":"Dis. Colon Rectum"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1097\/00000658-198403000-00016","article-title":"Anal carcinoma in patients with Crohn\u2019s disease","volume":"199","author":"Slater","year":"1984","journal-title":"Ann. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/00054725-200501000-00018","article-title":"Human papilloma virus infection in a recurrent squamous cell carcinoma associated with severe Cronh\u2019s disease","volume":"11","author":"Kuhlgatz","year":"2005","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.amjsurg.2004.04.013","article-title":"Malignant transformation of chronic perianal Crohn\u2019s fistula","volume":"189","author":"Bahadursingh","year":"2005","journal-title":"Am. J. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/BF02237203","article-title":"Is Hartmann\u2019s procedure safe in Crohn\u2019s disease?\u2014Report of three cases","volume":"43","author":"Cirincione","year":"2000","journal-title":"Dis. Colon Rectum"},{"key":"ref_26","first-page":"521","article-title":"Perianal fistulas in patients with Crohn\u2019s disease, Part 2: Surgical, endoscopic, and future therapies","volume":"14","author":"Gold","year":"2018","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.3748\/wjg.v21.i5.1394","article-title":"Management of perianal fistulas in Cohn\u2019s disease: An up-to-date review","volume":"21","author":"Marzo","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"American Gastroenterological Association Clinical Practice Committee (2003). American Gastroenterological Association Medical Position Statement: Perianal Crohn\u2019s Disease. Gastroenterology, 125, 1503\u20131507.","DOI":"10.1016\/S0016-5085(03)01060-6"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3109\/00365521.2010.536251","article-title":"Malignant transformation of perianal and enterocutaneous fistulas is rare: Results of 17 years of follow-up from the Netherlands","volume":"46","author":"Baars","year":"2011","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s11605-010-1402-9","article-title":"Intestinal Cancer Risk in Crohn\u2019s Disease: A Meta-Analysis","volume":"15","author":"Laukoetter","year":"2011","journal-title":"J. Gastrointest. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11605-009-1061-x","article-title":"Malignant transformation in perianal fistulas of crohn\u2019s disease: A systematic review of literature","volume":"14","author":"Thomas","year":"2010","journal-title":"J. Gastrointest. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.suronc.2013.08.002","article-title":"A systematic review of anal squamous cell carcinoma in inflammatory bowel disease","volume":"22","author":"Slesser","year":"2013","journal-title":"Surg. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1093\/ecco-jcc\/jjx035","article-title":"Anal Neoplasia in Inflammatory Bowel Disease: Classification Proposal, Epidemiology, Carcinogenesis, and Risk Management Perspectives","volume":"11","author":"Wisniewski","year":"2017","journal-title":"J. Crohns Colitis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/j.1572-0241.2007.01582.x","article-title":"Higher incidence of abnormal Pap smears in women with inflammatory bowel disease","volume":"103","author":"Kane","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1038\/ctg.2016.8","article-title":"Anal Neoplasia in Inflammatory Bowel Disease Is Associated With HPV and Perianal Disease","volume":"7","author":"Ruel","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1177\/014107688808100411","article-title":"Carcinoma in anal Crohn\u2019s disease: Discussion paper","volume":"81","author":"Ball","year":"1988","journal-title":"J. R. Soc. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1054\/bjoc.2001.1931","article-title":"Non-melanoma skin cancers and glucocorticoid therapy","volume":"85","author":"Karagas","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/MIB.0000000000000243","article-title":"Cancer and immunomodulators in inflammatory bowel diseases","volume":"21","author":"Biancone","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1002\/jmri.21186","article-title":"MRI appearance of perianal carcinoma in Crohn\u2019s disease","volume":"26","author":"Lad","year":"2007","journal-title":"J. Magn. Reson. Imaging"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:39:10Z","timestamp":1760161150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cancers13061445"],"URL":"https:\/\/doi.org\/10.3390\/cancers13061445","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]}}}