{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:00:13Z","timestamp":1792699213779,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence in recent decades. With higher cure rates in younger populations, long-term survivors may live with acute- and long-term toxicity, leading to increased interest in de-escalation treatment strategies for HPV-related OPSCC. Herein, we have examined the current landscape of clinical trials in this context.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A review of active clinical trials related to de-escalation of HPV-associated OPSCC treatment was performed using the clinicaltrials.gov database from inception to January 2022. A search using the key words \u201coropharyngeal cancer\u201d and \u201cHPV\u201d was completed. Three investigators independently reviewed each trial, with any discrepancies settled by a fourth. Data collected from each study included study phase, study design, primary, and secondary endpoints, and de-escalation treatment strategies. A final 24 articles were selected for full text review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Many trials (n=19, 79%) were non-randomized, and most studies employed a phase II design (n=14, 58%). Only 13% (n=3) were randomized trials, and 8% (n=2) included a phase III component. The most frequent primary endpoint was progression-free survival (PFS) (n=9, 37.5%). With regards to the identified de-escalation strategies, all the studies (n=24) had at least one component assessing changes in RT dose\/fractionation and\/or a reduction in RT volumes. A smaller percentage of trials assessed surgical interventions (n=9, 37.5%) and\/or changes in systemic therapy (n=8, 33.3%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A small number of randomized trials are underway, and a transition to more randomized phase III trials in the future will be important to change clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.1067321","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T06:26:10Z","timestamp":1671776770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["What is the future of treatment de-escalation for HPV-positive oropharyngeal cancer? A review of ongoing clinical trials"],"prefix":"10.3389","volume":"12","author":[{"given":"Emma A.","family":"Mensour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintha","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seliya","family":"Mawani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houda","family":"Bahig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pencilla","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Jasper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-022-09407-5","article-title":"Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common","volume":"22","author":"Wang","year":"2022","journal-title":"BMC Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-21100-8_1","article-title":"Epidemiology of HPV-associated oropharyngeal squamous cell carcinoma","volume":"50","author":"Gollin","year":"2015","journal-title":"Hum Papillomavirus (HPV)-Associated Oropharyngeal 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