Table 2 Adaptive de-escalation treatment in HPV-positive OSCC.

Beginning of the study	NCT code	Short name	Phase	HPV diagnosis	Strategy for patients with HPV OSCC	Primary aim of the study	Study title	Recruiting	Ongoing	Completed
2009	NCT01088802		2	HPV DNA and/or p16INK4A	De-intensification of radiation dose	Comparable therapeutic outcome with lower long-term toxicity	Treatment de-intensification for squamous cell carcinoma of the oropharynx		X
2010	NCT01084083		2	HPV ISH and/or p16INK4A	Induction chemotherapy, reduction of radiation dose, followed by Cetuximab	Comparable therapy outcome	Induction chemotherapy followed by Cetuximab and radiation in HPV-associated resectable stage III/IV oropharyngeal cancer			X
2011	NCT01302834	RTOG-1016	3	p16INK4A	Substitution of Cisplatin by Cetuximab in RCT	Comparable therapy outcome	Radiation therapy with Cisplatin or Cetuximab in treating patients with oropharyngeal cancer		X
	NCT01530997		2	HPV DNA and/or p16INK4A	Reduction of chemotherapy and radiation dose, limited neck dissection	Comparable therapy outcome with lower toxicity	Phase-II-study of de-intensification of radiation and chemotherapy for low-risk HPV-related oropharyngeal squamous cell carcinoma		X
2012	NCT01530997		2	HPV DNA and/or p16INK4A	Reduction of chemotherapy and radiation dose	Comparable therapy outcome with lower toxicity	De-intensification of radiation and chemotherapy for low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma		X
	NCT01687413	ADEPT	3	p16INK4A	Postoperative radiotherapy with and without Cisplatin (in R0 and N>0)	Comparable therapy outcome and toxicity	Post-operative adjuvant therapy de-intensification trial for human papilloavirus-related, p16+ oropharynx cancer		X
	NCT01716195		2	p16INK4A	Induction chemotherapy (Carboplatin/ Paclitaxel), reduction of radiation dose and chemotherapy (Paclitaxel)	Comparable therapy outcome with lower toxicity	Induction chemotherapy followed by chemoradiotherapy for head and neck cancer		X
2012	NCT01706939	Quarterback Trial	3	HPV DNA and p16INK4A	Reduction of the radiation dose (56 Gy) with weekly Carboplatin vs. 70 Gy radiation dose and weekly Carboplatin	Comparable therapy outcome with reduced radiation dose	The Quarterback Trial: A randomized phase III clinical trial comparing reduced and standard radiation therapy doses for locally advanced HPV-positive oropharynx cancer		X
	NCT01663259			HPV DNA and/or p16INK4A	Substitution of Cisplatin by Cetuximab in radiochemotherapy	Comparable therapy outcome with lower toxicity	Reduced intensity therapy for oropharyngeal cancer in non-smoking HPV 16 positive patients		X
2013	NCT01898494	ECOG 3311	2	p16INK4A	Reduction of the radiation dose after transoral tumor resection (advanced OSCC)	Comparable therapy outcome	Transoral surgery followed by low-dose or standard-dose radiation therapy with or without chemotherapy in treating patients with HPV positive stage III-IVA oropharyngeal cancer		X
	NCT01874171	De-ESCALaTE-HPV	3	p16INK4A	Substitution of Cisplatin by Cetuximab in radiochemotherapy	Improved quality of life and reduced toxicity	Determination of Cetuximab versus Cisplatin early and late toxicity events in HPV+ OPSCC		X
2013	NCT01891695		1	p16INK4A	Reduction of the radiation dose for cervical lymph nodes (39.6 Gy) with clinical N0	Comparable therapy outcome with lower toxicity	A pilot single arm study of intensity modulated radiation therapy elective nodal dose de-escalation for HPV-associated squamous cell carcinoma or the oropharynx		X
	NCT01855451	TROG12.01	3	p16INK4A	Substitution of Cisplatin by Cetuximab in radiochemotherapy	Comparable quality of life and toxicity	Weekly Cetuximab/RT versus weekly Cisplatin/RT in HPV-associated oropharyngeal squamous cell carcinoma (HPV Oropharynx)	X	X
2014	NCT02281955		2	HPV DNA and/or p16INK4A	Reduction of chemotherapy and radiation dose (follow-up study of NCT01530997)	Comparable therapy outcome with lower toxicity	De-intensification of radiation and chemotherapy for low-risk HPV-related oropharyngeal SCC: Follow-up study	X	X
	NCT02072148	SIRS TRIAL	2	HPV DNA and p16INK4A	Surgery alone for low-risk patients	Comparable therapy outcome	The Sinai Robotic Surgery Trial in HPV-positive oropharyngeal squamous cell carcioma (SCCA)	X	X
2014	NCT02254278		2	p16INK4A	Reduction of radiation dose with or without Cisplatin	Comparable therapy outcome with lower toxicity	A randomized phase II trial for patients with p16 positive, non-smoking associated, locoregionally advanced oropharyngeal cancer		X
	NCT02215265	PATHOS	2+3	HPV (no further data)	Reduction of the adjuvant therapy after transoral resection	Improvement of swallowing	Post-operative adjuvant treatment for HPV-positive tumours		X
2016	NCT02784288		2	p16INK4A	Treatment stratification after pathology of neck dissection	Improvement of the quality of life	Phase II treatment stratification trial using neck dissection-driven selection to improve quality of life for low-risk patients with HPV+ oropharyngeal squamous cell cancer
2017	NCT03210103	ORATOR2		HPV DNA or p16INK4A	Primary de-intensified radiotherapy vs. transoral surgery with neck dissection (+/-) adjuvant radiotherapy	Comparable therapy outcome	A randomized trial of treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma: radiotherapy vs. trans-oral surgery
2017	NCT03215719		2	p16INK4A	Reduction of radiation dose in responders during standard radiotherapy	Comparable therapy outcome	Adaptive treatment de-escalation in favorable risk HPV-positive oropharyngeal carcinoma	X	X