{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:36:39Z","timestamp":1789770999437,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,11,18]],"date-time":"2003-11-18T00:00:00Z","timestamp":1069113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background.<\/jats:title><jats:p>Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV\u2010positive and HPV\u2010negative tumors in this region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16<jats:sup>INK4A<\/jats:sup>, p21<jats:sup>CIP1\/WAF1<\/jats:sup>, p27<jats:sup>KIP1<\/jats:sup>, and cyclinD1) by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down\u2010regulated p27 tended to have down\u2010regulated pRb and p21.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>HPV\u2010positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV\u2010negative tumors. \u00a9 2004 Wiley Periodicals, Inc. Head and Neck 26: 1\u20139, 2004<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.10335","type":"journal-article","created":{"date-parts":[[2004,1,12]],"date-time":"2004-01-12T08:00:38Z","timestamp":1073894438000},"page":"1-9","source":"Crossref","is-referenced-by-count":91,"title":["The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil"],"prefix":"10.1002","volume":"26","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol H.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne E.","family":"Cossart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"McNeil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Scolyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara R.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11,18]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-199505000-00007"},{"key":"e_1_2_5_3_2","first-page":"697","article-title":"Biomarkers in upper aerodigestive tract tumorigenesis: a review","volume":"3","author":"Shin DM","year":"1994","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2391(97)90495-X"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940701)74:1<152::AID-CNCR2820740124>3.0.CO;2-K"},{"key":"e_1_2_5_6_2","first-page":"4813","article-title":"PRAD\u20101\/cyclin D1 amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas","volume":"54","author":"Jares P","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.4.2686"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19970201)79:3<595::AID-CNCR24>3.0.CO;2-Y"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000520)89:3<300::AID-IJC14>3.0.CO;2-G"},{"key":"e_1_2_5_10_2","first-page":"145","article-title":"Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma","volume":"152","author":"Wilczynski SP","year":"1998","journal-title":"Am J Pathol"},{"key":"e_1_2_5_11_2","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_5_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2001.6306"},{"key":"e_1_2_5_13_2","first-page":"755","article-title":"Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival","volume":"2","author":"Haraf DJ","year":"1996","journal-title":"Clin Can Res"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-10-2769"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.18.1477"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910520212"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.1.225"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000601)86:5<695::AID-IJC15>3.0.CO;2-C"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-76-4-1057"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12292090"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00069.x"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970822)74:4<383::AID-IJC4>3.0.CO;2-R"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65689-1"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-60592-5_3"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00041-0"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1993.01880170080017"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20011201)92:11<2875::AID-CNCR10130>3.0.CO;2-7"},{"key":"e_1_2_5_28_2","first-page":"F55","article-title":"Papillomavirus infection\u2014a major cause of human cancers","volume":"1288","author":"zur Hausen H","year":"1996","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.1031"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/387296a0"},{"key":"e_1_2_5_31_2","first-page":"2810","article-title":"Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue","volume":"5","author":"Bova RJ","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1998.4345"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199908000-00029"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010815)92:4<805::AID-CNCR1386>3.0.CO;2-9"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhed.10335","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.10335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T03:58:38Z","timestamp":1700193518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.10335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,18]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1]]}},"alternative-id":["10.1002\/hed.10335"],"URL":"https:\/\/doi.org\/10.1002\/hed.10335","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,18]]}}}