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The treatment regimens currently in place cause significant long-term toxicities. Studies have transitioned from mortality-based outcomes to patient-reported outcomes assessing quality of life. There are many completed and ongoing trials investigating alternative therapy regimens or de-escalation strategies to minimize the negative secondary effects while maintaining overall survival and disease-free survival. The goal of this review is to discuss the most recent advancements within the field while summarizing and reviewing the available evidence.<\/jats:p>","DOI":"10.3390\/curroncol29050295","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:59:37Z","timestamp":1652875177000},"page":"3668-3697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma\u2014Where Are We Now?"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7896-8367","authenticated-orcid":false,"given":"Jennifer A.","family":"Silver","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University Health Centre, Montreal, QC H4A 3JI, Canada"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena","family":"Turkdogan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University Health Centre, Montreal, QC H4A 3JI, Canada"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-2494","authenticated-orcid":false,"given":"Catherine F.","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University Health Centre, Montreal, QC H4A 3JI, Canada"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thavakumar","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University Health Centre, Montreal, QC H4A 3JI, Canada"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"},{"name":"Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H4A 3JI, Canada"},{"name":"Lady-Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"},{"name":"Segal Cancer Centre, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University Health Centre, Montreal, QC H4A 3JI, Canada"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, McGill University, Montreal, QC H4A 3JI, Canada"},{"name":"Research Institute of McGill University Health Center, McGill University, Montreal, QC H4A 3JI, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","unstructured":"Global Cancer Observatory (2020). International Agency for Research on Cancer, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1200\/JCO.2011.36.4596","article-title":"Human papillomavirus and rising oropharyngeal cancer incidence in the United States","volume":"29","author":"Chaturvedi","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_3","unstructured":"(2022, March 12). Cancer Facts & Figures 2022. Available online: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/annual-cancer-facts-and-figures\/2022\/2022-cancer-facts-and-figures.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1470-2045(10)70017-6","article-title":"HPV-associated head and neck cancer: A virus-related cancer epidemic","volume":"11","author":"Marur","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1200\/JCO.2015.61.6995","article-title":"Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma","volume":"33","author":"Gillison","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ijrobp.2013.08.029","article-title":"Review of the clinical and biologic aspects of human papillomavirus-positive squamous cell carcinomas of the head and neck","volume":"88","author":"Blitzer","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3201\/eid2005.131311","article-title":"Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States","volume":"20","author":"Steinau","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa0912217","article-title":"Human papillomavirus and survival of patients with oropharyngeal cancer","volume":"363","author":"Ang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_9","unstructured":"(2022, March 12). HPV-Associated Cancer Statistics, Available online: https:\/\/www.cdc.gov\/cancer\/hpv\/statistics\/."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Scarth, J.A., Patterson, M.R., Morgan, E.L., and Macdonald, A. (2021). The human papillomavirus oncoproteins: A review of the host pathways targeted on the road to transformation. J. Gen. Virol., 102.","DOI":"10.1099\/jgv.0.001540"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djn011","article-title":"Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial","volume":"100","author":"Fakhry","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11912-019-0799-x","article-title":"Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications","volume":"21","author":"Zanoni","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.suronc.2018.08.003","article-title":"Transoral surgery (TOS) in oropharyngeal cancer: Different tools, a single mini-invasive philosophy","volume":"27","author":"Tirelli","year":"2018","journal-title":"Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.radonc.2011.05.036","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site","volume":"100","author":"Blanchard","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1200\/JCO.2004.08.021","article-title":"Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma","volume":"22","author":"Denis","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0140-6736(00)90011-4","article-title":"Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer","volume":"355","author":"Pignon","year":"2000","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.radonc.2009.04.014","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients","volume":"92","author":"Pignon","year":"2009","journal-title":"Radiother. Oncol."},{"key":"ref_18","unstructured":"(2022). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) for Head and Neck Cancers V.1-2022\u00a9, National Comprehensive Cancer Network, Inc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/MOO.0b013e3283509735","article-title":"Oropharyngeal cancer\u2014Is it time to change management according to human papilloma virus status?","volume":"20","author":"Mehanna","year":"2012","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/j.ijrobp.2009.06.090","article-title":"Radiotherapy dose-volume effects on salivary gland function","volume":"76","author":"Deasy","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1001\/jamaoto.2015.0347","article-title":"Transoral robotic surgery alone for oropharyngeal cancer: Quality-of-life outcomes","volume":"141","author":"Choby","year":"2015","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1200\/JCO.2007.14.8841","article-title":"Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: An RTOG analysis","volume":"26","author":"Machtay","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gupta, T., Kannan, S., Ghosh-Laskar, S., and Agarwal, J.P. (2018). Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and\/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200137"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/jso.26688","article-title":"Therapeutic strategies for systemic therapies of human papillomavirus-related oropharyngeal cancer","volume":"124","author":"Hung","year":"2021","journal-title":"J. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fonc.2020.00007","article-title":"The Slippery Role of Induction Chemotherapy in Head and Neck Cancer: Myth and Reality","volume":"10","author":"Ferrari","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.oraloncology.2019.06.015","article-title":"Induction chemotherapy in head and neck cancers: Results and controversies","volume":"95","author":"Gau","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1288\/00005537-197902000-00016","article-title":"Head and neck complications of systemic cancer chemotherapy","volume":"89","author":"Goepfert","year":"1979","journal-title":"Laryngoscope"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1200\/JCO.2013.54.6309","article-title":"Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer","volume":"32","author":"Cohen","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1002\/hed.26147","article-title":"Neoadjuvant chemotherapy followed by surgery for HPV-associated locoregionally advanced oropharynx cancer","volume":"42","author":"Sadeghi","year":"2020","journal-title":"Head Neck"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/hed.26022","article-title":"Pathologic response to neoadjuvant chemotherapy in HPV-associated oropharynx cancer","volume":"42","author":"Sadeghi","year":"2020","journal-title":"Head Neck"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11864-015-0362-4","article-title":"Surgery Versus Radiotherapy for Early Oropharyngeal Tumors: A Never-Ending Debate","volume":"16","author":"Monnier","year":"2015","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/lary.20694","article-title":"The mandibulotomy: Friend or foe? Safety outcomes and literature review","volume":"119","author":"Dziegielewski","year":"2009","journal-title":"Laryngoscope"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/hed.21290","article-title":"Complications and functional outcomes following complex oropharyngeal reconstruction","volume":"32","author":"Zafereo","year":"2010","journal-title":"Head Neck"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1002\/hed.21669","article-title":"Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: A United States multicenter study","volume":"33","author":"Haughey","year":"2011","journal-title":"Head Neck"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/hed.23610","article-title":"Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer","volume":"37","author":"Chen","year":"2015","journal-title":"Head Neck"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/lary.24712","article-title":"A systematic review of transoral robotic surgery and radiotherapy for early oropharynx cancer: A systematic review","volume":"124","author":"Byrd","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00405-013-2501-5","article-title":"Transoral laser resection versus lip-split mandibulotomy in the management of oropharyngeal squamous cell carcinoma (OPSCC): A case match study","volume":"271","author":"Williams","year":"2014","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/hed.23809","article-title":"Functional outcomes, feasibility, and safety of resection of transoral robotic surgery: Single-institution series of 35 consecutive cases of transoral robotic surgery for oropharyngeal squamous cell carcinoma","volume":"37","author":"Busch","year":"2015","journal-title":"Head Neck"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.14639\/0392-100X-2199","article-title":"Trans-oral robotic surgery for the management of oropharyngeal carcinomas: A 9-year institutional experience","volume":"39","author":"Meccariello","year":"2019","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S1470-2045(19)30410-3","article-title":"Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): An open-label, phase 2, randomised trial","volume":"20","author":"Nichols","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1200\/JCO.21.01961","article-title":"Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial","volume":"40","author":"Nichols","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nichols, A.C., Lang, P., Prisman, E., Berthelet, E., Tran, E., Hamilton, S., Wu, J., Fung, K., de Almeida, J.R., and Bayley, A. (2020). Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): Study protocol for a randomized phase II trial. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6607-z"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.ijrobp.2021.09.013","article-title":"A Randomized Trial of Radiotherapy vs. Trans-Oral Surgery for Treatment De-Escalation in HPV-Associated Oropharyngeal Squamous Cell Carcinoma (ORATOR2)","volume":"111","author":"Palma","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1200\/JCO.19.00463","article-title":"Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma","volume":"37","author":"Ma","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/hed.26477","article-title":"Human papillomavirus oropharynx carcinoma: Aggressive de-escalation of adjuvant therapy","volume":"43","author":"Moore","year":"2021","journal-title":"Head Neck"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1200\/JCO.2013.53.9163","article-title":"Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234","volume":"32","author":"Harari","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ijrobp.2019.11.021","article-title":"A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx","volume":"106","author":"Lukens","year":"2020","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1200\/JCO.21.01752","article-title":"Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311)","volume":"40","author":"Ferris","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ijrobp.2008.06.1222","article-title":"Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy","volume":"72","author":"Kim","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0360-3016(99)00247-3","article-title":"Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer","volume":"45","author":"Eisbruch","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/onco.13742","article-title":"De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial","volume":"26","author":"Miles","year":"2021","journal-title":"Oncologist"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Owadally, W., Hurt, C., Timmins, H., Parsons, E., Townsend, S., Patterson, J., Hutcheson, K., Powell, N., Beasley, M., and Palaniappan, N. (2015). PATHOS: A phase II\/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1598-x"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105332","DOI":"10.1016\/j.oraloncology.2021.105332","article-title":"Implementation of human papillomavirus circulating tumor DNA to identify recurrence during treatment de-escalation","volume":"121","author":"Haring","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1200\/JCO.20.03128","article-title":"Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002)","volume":"39","author":"Yom","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/jnci\/djaa184","article-title":"Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial","volume":"113","author":"Riaz","year":"2021","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nrc2344","article-title":"Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability","volume":"8","author":"Bristow","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.ijrobp.2015.08.033","article-title":"Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma","volume":"93","author":"Chera","year":"2015","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1001\/archotol.1991.01870180037007","article-title":"Standardizing Neck Dissection Terminology: Official Report of the Academy\u2019s Committee for Head and Neck Surgery and Oncology","volume":"117","author":"Robbins","year":"1991","journal-title":"Arch. Otolaryngol.\u2013Head Neck Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1470-2045(13)70011-1","article-title":"Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): A randomised phase 3 trial","volume":"14","author":"Haddad","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1002\/cncr.31338","article-title":"Mature results of a prospective study of deintensified chemoradiotherapy for low-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma","volume":"124","author":"Chera","year":"2018","journal-title":"Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1200\/JCO.19.01007","article-title":"Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma","volume":"37","author":"Chera","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0140-6736(18)32779-X","article-title":"Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): A randomised, multicentre, non-inferiority trial","volume":"393","author":"Gillison","year":"2019","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1056\/NEJMoa053422","article-title":"Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck","volume":"354","author":"Bonner","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0140-6736(18)32752-1","article-title":"Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): An open-label randomised controlled phase 3 trial","volume":"393","author":"Mehanna","year":"2019","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.ijrobp.2021.04.015","article-title":"Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01)\u2014A Trans-Tasman Radiation Oncology Group Study","volume":"111","author":"Rischin","year":"2021","journal-title":"Int. J Radiat. Oncol. Biol. Phys."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1002\/hed.24526","article-title":"Neoadjuvant chemotherapy and transoral surgery as a definitive treatment for oropharyngeal cancer: A feasible novel approach","volume":"38","author":"Sadeghi","year":"2016","journal-title":"Head Neck"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.oraloncology.2012.07.015","article-title":"Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer","volume":"49","author":"Huang","year":"2013","journal-title":"Oral Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.ijrobp.2009.04.006","article-title":"Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: Clinical outcomes and patterns of failure","volume":"76","author":"Daly","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1200\/JCO.2016.68.3300","article-title":"E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx\u2014ECOG-ACRIN Cancer Research Group","volume":"35","author":"Marur","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.oraloncology.2019.06.021","article-title":"Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial","volume":"95","author":"Misiukiewicz","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/annonc\/mdy522","article-title":"OPTIMA: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer","volume":"30","author":"Seiwert","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S1470-2045(17)30246-2","article-title":"Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: A single-arm, phase 2 study","volume":"18","author":"Chen","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1002\/cncr.30598","article-title":"The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma","volume":"123","author":"An","year":"2017","journal-title":"Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.oraloncology.2017.08.020","article-title":"Appraisal of the AJCC 8th edition pathologic staging modifications for HPV-positive oropharyngeal cancer, a study of the National Cancer Data Base","volume":"73","author":"Zhan","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1177\/0194599820910431","article-title":"Clinical vs Microscopic Extranodal Extension and Survival in Oropharyngeal Carcinoma in the Human Papillomavirus Era","volume":"162","author":"Gal","year":"2020","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/lary.28059","article-title":"Extranodal extension is a strong prognosticator in HPV-positive oropharyngeal squamous cell carcinoma","volume":"130","author":"Bauer","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1056\/NEJMoa071028","article-title":"Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer","volume":"357","author":"Vermorken","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3389\/fonc.2020.00761","article-title":"Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma","volume":"10","author":"Hanemaaijer","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_79","first-page":"47","article-title":"The failure of cetuximab-based de-intensified regimes for HPV-positive OPSCC: A radiobiologists perspective","volume":"17","author":"Rieckmann","year":"2019","journal-title":"Clin. Transl. Radiat. 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