{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:38:15Z","timestamp":1769837895732,"version":"3.49.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head Neck Oncol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Oral epithelial dysplasia (OED) has a malignant potential. Therapeutic options for OED remain both limited and without good evidence. Despite surgery being the most common method of treating OED, recurrence and potentially significant morbidity remain problematic. Consequently, there has been much interest in non-surgical treatments for OED. Cyclo-oxygenase (COX) up-regulation is known to occur in the dysplasia-carcinoma sequence and evidence now exists that COX-2 is a prognostic marker of malignant transformation in OED. COX-inhibitors are therefore considered a potential therapeutic strategy for treating this condition. We aimed to provide both proof of principal evidence supporting the effect of topical COX inhibition, and determine the feasibility of recruitment to an OED chemoprevention trial in the UK.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Recruitment of 40 patients with oral leukoplakia to 4 study arms was planned. The total daily dose of Aspirin would increase in each group and be used in the period between initial diagnostic and follow-up biopsies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>During the 15-month recruitment period, 15\/50 screened patients were eligible for recruitment, and 13 (87%) consented. Only 1 had OED diagnosed on biopsy. 16 patients were intolerant of, or already taking Aspirin and 16 patients required no biopsy. Initial recruitment was slow, as detection relied on clinicians identifying potentially eligible patients. Pre-screening new patient letters and directly contacting patients listed for biopsies improved screening of potentially eligible patients. However, as the incidence of OED was so low, it had little impact on trial recruitment. The trial was terminated, as recruitment was unlikely to be achieved in a single centre.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This feasibility trial has demonstrated the low incidence of OED in the UK and the difficulties in conducting a study because of this. With an incidence of around 1.5\/100,000\/year and a high proportion of those patients already taking or intolerant of Aspirin, a large multi-centred trial would be required to fulfil the recruitment for this study. The ability of topical non-steroidal anti-inflammatory drugs to modify COX and prostaglandin expression remains an important but unanswered question. Collaboration with centres in other parts of the world with higher incidences of the disease may be required to ensure adequate recruitment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>ISRCTN<\/jats:title>\n            <jats:p>31503555.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1758-3284-4-40","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T12:15:25Z","timestamp":1348229725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Feasibility of recruitment to an oral dysplasia trial in the United Kingdom"],"prefix":"10.1186","volume":"4","author":[{"given":"Paul","family":"Nankivell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Langman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisham","family":"Mehanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,6,25]]},"reference":[{"issue":"10","key":"268_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","volume":"36","author":"S Warnakulasuriya","year":"2007","unstructured":"Warnakulasuriya S, Johnson NW, der Waal van I: Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007, 36 (10): 575-580. 10.1111\/j.1600-0714.2007.00582.x.","journal-title":"J Oral Pathol Med"},{"key":"268_CR2","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0030-4220(86)90422-6","volume":"61","author":"JE Bouquot","year":"1986","unstructured":"Bouquot JE, Gorlin RJ: Leukoplakia, lichen planus, and other oral keratoses in 23,616 white Americans over the age of 35\u2009years. Oral Surg Oral Med Oral Pathol. 1986, 61: 373-381. 10.1016\/0030-4220(86)90422-6.","journal-title":"Oral Surg Oral Med Oral Pathol"},{"key":"268_CR3","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1002\/1097-0142(197510)36:4<1386::AID-CNCR2820360430>3.0.CO;2-7","volume":"36","author":"CA Waldron","year":"1975","unstructured":"Waldron CA, Shafer WG: Leukoplakia revisited. A clinicopathologic study 3256 oral leukoplakias. Cancer. 1975, 36: 1386-1392. 10.1002\/1097-0142(197510)36:4<1386::AID-CNCR2820360430>3.0.CO;2-7.","journal-title":"Cancer"},{"key":"268_CR4","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.tripleo.2005.07.024","volume":"101","author":"J-J Lee","year":"2006","unstructured":"Lee J-J, Hung H-C, Cheng S-J, et al: Carcinoma and dysplasia in oral leukoplakias in Taiwan: prevalence and risk factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006, 101: 472-480. 10.1016\/j.tripleo.2005.07.024.","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"268_CR5","first-page":"133","volume":"25","author":"JE Bouquot","year":"1994","unstructured":"Bouquot JE, Whitaker SB: Oral leukoplakia - rationale for diagnosis and prognosis of its clinical subtypes or \"phases\". Quintessence Int. 1994, 25: 133-140.","journal-title":"Quintessence Int"},{"key":"268_CR6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1600-0714.2006.00491.x","volume":"36","author":"SS Hsue","year":"2007","unstructured":"Hsue SS, Wang WC, Chen CH, et al: Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: a follow-up study based in a Taiwanese hospital. J Oral Pathol Med. 2007, 36: 25-29.","journal-title":"J Oral Pathol Med"},{"key":"268_CR7","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1002\/1097-0142(19840201)53:3<563::AID-CNCR2820530332>3.0.CO;2-F","volume":"53","author":"SJ Silverman","year":"1984","unstructured":"Silverman SJ, Gorsky M, Lozada F: Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer. 1984, 53: 563-568. 10.1002\/1097-0142(19840201)53:3<563::AID-CNCR2820530332>3.0.CO;2-F.","journal-title":"Cancer"},{"key":"268_CR8","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/hed.21131","volume":"31","author":"HM Mehanna","year":"2009","unstructured":"Mehanna HM, Rattay T, Smith J, et al: Treatment and follow-up of oral dysplasia - a systematic review and meta-analysis. Head Neck. 2009, 31: 1600-1609. 10.1002\/hed.21131.","journal-title":"Head Neck"},{"key":"268_CR9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3322\/caac.20121","volume":"61","author":"R Siegel","year":"2011","unstructured":"Siegel R, Ward E, Brawley O, et al: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011, 61: 212-236. 10.3322\/caac.20121.","journal-title":"CA Cancer J Clin"},{"key":"268_CR10","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s11912-010-0150-z","volume":"13","author":"P Nankivell","year":"2011","unstructured":"Nankivell P, Mehanna H: Oral Dysplasia: Biomarkers, Treatment, and Follow-up. Curr Oncol Rep. 2011, 13: 145-152. 10.1007\/s11912-010-0150-z.","journal-title":"Curr Oncol Rep"},{"key":"268_CR11","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.oraloncology.2010.02.016","volume":"46","author":"I Der Waal Van","year":"2010","unstructured":"Der Waal Van I: Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol. 2010, 46: 423-425. 10.1016\/j.oraloncology.2010.02.016.","journal-title":"Oral Oncol"},{"key":"268_CR12","first-page":"CD001829","volume":"18","author":"G Lodi","year":"2006","unstructured":"Lodi G, Sardella A, Bez C, et al: Interventions for treating oral leukoplakia. Cochrane Database Syst Rev. 2006, 18: CD001829-","journal-title":"Cochrane Database Syst Rev"},{"key":"268_CR13","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/j.1600-0714.2009.00782.x","volume":"38","author":"PG Arduino","year":"2009","unstructured":"Arduino PG, Surace A, Carbone M, et al: Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up. J Oral Pathol Med. 2009, 38: 540-544. 10.1111\/j.1600-0714.2009.00782.x.","journal-title":"J Oral Pathol Med"},{"key":"268_CR14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.oraloncology.2004.06.010","volume":"41","author":"PS van der Hem","year":"2005","unstructured":"van der Hem PS, Nauta JM, van der Wal JE, et al: The results of CO2 laser surgery in patients with oral leukoplakia: a 25\u2009year follow up. Oral Oncol. 2005, 41: 31-37. 10.1016\/j.oraloncology.2004.06.010.","journal-title":"Oral Oncol"},{"key":"268_CR15","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1159\/000130872","volume":"70","author":"S Zhang","year":"2008","unstructured":"Zhang S, Du Y, Tao J, et al: Expression of cytosolic phospholipase A2 and cyclooxygenase 2 and their significance in human oral mucosae, dysplasias and squamous cell carcinomas. ORL J Otorhinolaryngol Relat Spec. 2008, 70: 242-248. 10.1159\/000130872.","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"key":"268_CR16","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.oraloncology.2004.09.009","volume":"41","author":"M Shibata","year":"2005","unstructured":"Shibata M, Kodani I, Osaki M, et al: Cyclo-oxygenase-1 and \u22122 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol. 2005, 41: 304-312. 10.1016\/j.oraloncology.2004.09.009.","journal-title":"Oral Oncol"},{"key":"268_CR17","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1002\/1097-0142(20011001)92:7<1888::AID-CNCR1706>3.0.CO;2-Z","volume":"92","author":"CA Nathan","year":"2001","unstructured":"Nathan CA, Leskov IL, Lin M, et al: COX-2 expression in dysplasia of the head and neck: correlation with elF4E. Cancer. 2001, 92: 1888-1895. 10.1002\/1097-0142(20011001)92:7<1888::AID-CNCR1706>3.0.CO;2-Z.","journal-title":"Cancer"},{"key":"268_CR18","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1002\/cncr.10333","volume":"94","author":"NJ Shaheen","year":"2002","unstructured":"Shaheen NJ, Straus WL, Sandler RS: Chemoprevention of gastrointestinal malignancies with nonsteroidal antiinflammatory drugs. Cancer. 2002, 94: 950-963. 10.1002\/cncr.10333.","journal-title":"Cancer"},{"key":"268_CR19","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1158\/1940-6207.CAPR-07-0003","volume":"1","author":"LJ Wirth","year":"2008","unstructured":"Wirth LJ, Krane JF, Li Y, et al: A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions. Cancer Prev Res (Phila). 2008, 1: 339-348. 10.1158\/1940-6207.CAPR-07-0003.","journal-title":"Cancer Prev Res (Phila)"},{"key":"268_CR20","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1158\/1078-0432.CCR-07-4024","volume":"14","author":"VA Papadimitrakopoulou","year":"2008","unstructured":"Papadimitrakopoulou VA, William WN, Dannenberg AJ, et al: Pilot randomized phase II study of celecoxib in oral premalignant lesions. Clin Cancer Res. 2008, 14: 2095-2101. 10.1158\/1078-0432.CCR-07-4024.","journal-title":"Clin Cancer Res"},{"key":"268_CR21","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1158\/1078-0432.CCR-1020-3","volume":"10","author":"JL Mulshine","year":"2004","unstructured":"Mulshine JL, Atkinson JC, Greer RO, et al: Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. Clin Cancer Res. 2004, 10: 1565-1573. 10.1158\/1078-0432.CCR-1020-3.","journal-title":"Clin Cancer Res"},{"key":"268_CR22","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/sj.bdj.4808006","volume":"173","author":"TA Gregg","year":"1992","unstructured":"Gregg TA, Cowan CG, Kee F: Trends in the relative frequency of histologically diagnosed epithelial dysplasia and intra-oral carcinoma in Northern Ireland, 1975\u20131989. Br Dent J. 1992, 173: 234-236. 10.1038\/sj.bdj.4808006.","journal-title":"Br Dent J"},{"key":"268_CR23","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S1368-8375(03)00045-9","volume":"39","author":"MA Jaber","year":"2003","unstructured":"Jaber MA, Porter SR, Speight P, et al: Oral epithelial dysplasia: clinical characteristics of western European residents. Oral Oncol. 2003, 39: 589-596. 10.1016\/S1368-8375(03)00045-9.","journal-title":"Oral Oncol"},{"key":"268_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0714.2007.00579.x","volume":"37","author":"SS Napier","year":"2008","unstructured":"Napier SS, Speight PM: Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008, 37: 1-10.","journal-title":"J Oral Pathol Med"},{"key":"268_CR25","first-page":"124","volume":"12","author":"K Bhargava","year":"1975","unstructured":"Bhargava K, Smith LW, Mani NJ, et al: A follow up study of oral cancer and precancerous lesions in 57,518 industrial workers of Gujarat, India. Indian J Canc. 1975, 12: 124-129.","journal-title":"Indian J Canc"},{"key":"268_CR26","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/0030-4220(72)90319-2","volume":"34","author":"FS Mehta","year":"1972","unstructured":"Mehta FS, Shroff BC, Gupta PC, et al: Oral leukoplakia in relation to tobacco habits. A ten-year follow-up study of Bombay policemen. Oral Surg Oral Med Oral Pathol. 1972, 34: 426-433. 10.1016\/0030-4220(72)90319-2.","journal-title":"Oral Surg Oral Med Oral Pathol"},{"key":"268_CR27","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1002\/1097-0142(196910)24:4<832::AID-CNCR2820240427>3.0.CO;2-U","volume":"24","author":"FS Mehta","year":"1969","unstructured":"Mehta FS, Pindborg JJ, Gupta PC, et al: Epidemiologic and histologic study of oral cancer and leukoplakia among 50,915 villagers in India. Cancer. 1969, 24: 832-849. 10.1002\/1097-0142(196910)24:4<832::AID-CNCR2820240427>3.0.CO;2-U.","journal-title":"Cancer"},{"key":"268_CR28","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/j.1600-0528.1987.tb00479.x","volume":"15","author":"T Ax\u00e9ll","year":"1987","unstructured":"Ax\u00e9ll T: Occurrence of leukoplakia and some other oral white lesions among 20,333 adult Swedish people. Commun Dent Oral Epidemiol. 1987, 15: 46-51. 10.1111\/j.1600-0528.1987.tb00479.x.","journal-title":"Commun Dent Oral Epidemiol"},{"key":"268_CR29","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.1600-0528.1988.tb01781.x","volume":"16","author":"WF Hogewind","year":"1988","unstructured":"Hogewind WF, der Waal van I: Prevalence study of oral leukoplakia in a selected population of 1000 patients from The Netherlands. Commun Dent Oral Epidemiol. 1988, 16: 302-305. 10.1111\/j.1600-0528.1988.tb01781.x.","journal-title":"Commun Dent Oral Epidemiol"},{"key":"268_CR30","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/sj.bdj.4810069","volume":"194","author":"K Lim","year":"2003","unstructured":"Lim K, Moles DR, Downer MC, et al: Opportunistic screening for oral cancer and precancer in general dental practice: results of a demonstration study. Br Dent J. 2003, 194: 497-502. 10.1038\/sj.bdj.4810069. discussion493","journal-title":"Br Dent J"},{"key":"268_CR31","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/S1368-8375(03)00102-7","volume":"39","author":"S Petti","year":"2003","unstructured":"Petti S: Pooled estimate of world leukoplakia prevalence: a systematic review. Oral Oncol. 2003, 39: 770-780. 10.1016\/S1368-8375(03)00102-7.","journal-title":"Oral Oncol"},{"key":"268_CR32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/0964-1955(95)00012-7","volume":"31B","author":"R Kulasegaram","year":"1995","unstructured":"Kulasegaram R, Downer MC, Jullien JA, et al: Case-control study of oral dysplasia and risk habits among patients of a dental hospital. Eur J Cancer B Oral Oncol. 1995, 31B: 227-231.","journal-title":"Eur J Cancer B Oral Oncol"}],"container-title":["Head &amp; Neck Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-3284-4-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T19:44:17Z","timestamp":1630525457000},"score":1,"resource":{"primary":{"URL":"https:\/\/headandneckoncology.biomedcentral.com\/articles\/10.1186\/1758-3284-4-40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,25]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["268"],"URL":"https:\/\/doi.org\/10.1186\/1758-3284-4-40","relation":{},"ISSN":["1758-3284"],"issn-type":[{"value":"1758-3284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,25]]},"assertion":[{"value":"31 May 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"40"}}