{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:55:46Z","timestamp":1792068946117,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV\u2010related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and\/or p53. Survival outcomes included overall survival, disease\u2010free survival, disease\u2010specific survival, and progression\u2010free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%\u2013100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV\u2010positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16\u2010positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This systematic review suggests that women with HPV\u2010 and p16\u2010positive vaginal cancer have an improved prognosis compared with those with HPV\u2010 or p16\u2010negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aogs.14260","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T10:37:58Z","timestamp":1632220678000},"page":"2144-2156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-373X","authenticated-orcid":false,"given":"Christina L.","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna K.","family":"Bertoli","sequence":"additional","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freja L.","family":"Sand","sequence":"additional","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander K.","family":"Kj\u00e6r","sequence":"additional","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-8410","authenticated-orcid":false,"given":"Louise T.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne K.","family":"Kj\u00e6r","sequence":"additional","affiliation":[{"name":"Unit of Virus, Lifestyle, and Genes Danish Cancer Society Research Center  Copenhagen Denmark"},{"name":"Department of Gynecology, Rigshospitalet University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","first-page":"307","volume-title":"WHO classification of tumours of female reproductive organs","author":"Kurman RJ","year":"2014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2018.12.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.9778\/cmajo.20140005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.05.683"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12610"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.07.018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03727.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32078"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31139"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-19-1259"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2012.06.019"},{"key":"e_1_2_10_15_1","first-page":"5","article-title":"Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control","volume":"58","author":"Andl T","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318203cdba"},{"key":"e_1_2_10_17_1","first-page":"51","article-title":"Significance of p16 in site\u2010specific HPV positive and HPV negative head and neck squamous cell carcinoma","volume":"2","author":"Stephen JK","year":"2013","journal-title":"Cancer Clin Oncol"},{"key":"e_1_2_10_18_1","first-page":"3445","article-title":"p16 and p53 Protein expression as prognostic indicators of survival and disease recurrence from head and neck cancer","volume":"8","author":"Geisler SA","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2018.10.015"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0322"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-9378-5-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90409-8"},{"key":"e_1_2_10_23_1","first-page":"1655","article-title":"Carcinoma of the vulva: HPV and p53 mutations","volume":"9","author":"Lee YY","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.20"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2019.06.013"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-09-0981"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1916-0216-42-53"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602678"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.32"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-8258(03)00401-3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.12.449"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPMG0XIF7PEISO"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2016.27.e17"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000171"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.02.004"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31821bc615"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000000568"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-012-0291-0"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31827670c4"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1995.288"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2014.09.002"},{"key":"e_1_2_10_42_1","first-page":"432","article-title":"Human papillomavirus DNA in invasive carcinoma of the vagina","volume":"76","author":"Ikenberg H","year":"1990","journal-title":"Obstet Gynecol"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30516"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21961"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2015.10.001"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy522"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.05.019"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.05.016"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30855-1"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00520.x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30389"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27650"}],"container-title":["Acta Obstetricia et Gynecologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aogs.14260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:26:26Z","timestamp":1693182386000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/aogs.14260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,21]]},"references-count":52,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/aogs.14260"],"URL":"https:\/\/doi.org\/10.1111\/aogs.14260","archive":["Portico"],"relation":{},"ISSN":["0001-6349","1600-0412"],"issn-type":[{"value":"0001-6349","type":"print"},{"value":"1600-0412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,21]]},"assertion":[{"value":"2021-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}