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Induction Chemotherapy in Low-Risk HPV+ Oropharyngeal Cancer

  • Head and Neck Cancer (PL Swiecicki, Section Editor)
  • Published:
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Opinion statement

Human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in incidence, and has now become the most common head and neck cancer (HNC). Studies have demonstrated that HPV associated OPSCC is associated with a favorable prognosis compared with its HPV-negative counterparts, yet standard multimodality therapy is often associated with substantial acute and late treatment-related toxicity. While locoregional control is improved in HPV+ OPSCC, distant metastasis rate has gained recognition as a major cause of death in this population, with some studies suggesting similar rates as non-HPV-related cancers. Induction chemotherapy has been of long-standing interest in locoregionally advanced HNC, yet its use in combination with concomitant chemoradiation remains an area of controversy as a survival benefit remains unproven following randomized trials. Nevertheless, response to induction chemotherapy remains an important dynamic and prognostic biomarker, with response-adaptive de-intensified therapy in HPV+ OPSCC gaining traction in single-arm phase II studies demonstrating promising results. The emergence of immunotherapy in the recurrent/metastatic setting for HNC has led to enthusiasm to incorporate in the curative setting, yet its role remains undefined. Our institutional paradigm for HPV+ OPSCC incorporates induction therapy followed by risk and response adaptive locoregional treatment. Ultimately, the role of induction therapy in HPV+ OPSCC will need to be investigated in a randomized setting to be incorporated routinely into clinical practice.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mody MD, Rocco JW, Yom SS, Haddad RI, Saba NF. Head and neck cancer. Lancet. 2021. https://doi.org/10.1016/S0140-6736(21)01550-6.

  2. Chen AM, Daly ME, Farwell DG, Vazquez E, Courquin J, Lau DH, et al. Quality of life among long-term survivors of head and neck czancer treated by intensity-modulated radiotherapy. JAMA Otolaryngol Head Neck Surg. 2014;140(2):129–133. https://doi.org/10.1001/jamaoto.2013.5988.Chen AM, Daly ME, Farwell DG, Vazquez E, Courquin J, Lau DHet al. Quality of life among long-term survivors of head and neck cancer treated by intensity-modulated radiotherapy. JAMA Otolaryngol Head Neck Surg 2014;140(2):129-133. https://doi.org/10.1001/jamaoto.2013.5988.

  3. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, Forastiere A, Ang KK. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008;26(21):3582–9. https://doi.org/10.1200/jco.2007.14.8841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. El-Deiry M, Funk GF, Nalwa S, Karnell LH, Smith RB, Buatti JM, et al. Long-term quality of life for surgical and nonsurgical treatment of head and neck cancer. Arch Otolaryngol Head Neck Surg. 2005;131(10):879–85. https://doi.org/10.1001/archotol.131.10.879.

    Article  PubMed  Google Scholar 

  5. Givens DJ, Karnell LH, Gupta AK, Clamon GH, Pagedar NA, Chang KE, van Daele D, Funk GF. Adverse events associated with concurrent chemoradiation therapy in patients with head and neck cancer adverse events and CRT for head and neck cancer. JAMA Otolaryngol–Head Neck Surg. 2009;135(12):1209–17. https://doi.org/10.1001/archoto.2009.174.

    Article  Google Scholar 

  6. Hutcheson KA, Lewin JS, Barringer DA, Lisec A, Gunn GB, Moore MW, et al. Late dysphagia after radiotherapy-based treatment of head and neck cancer. Cancer. 2012;118(23):5793–9. https://doi.org/10.1002/cncr.27631.

    Article  PubMed  Google Scholar 

  7. Lin A, Kim HM, Terrell JE, Dawson LA, Ship JA, Eisbruch A. Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study. Int J Radiat Oncol Biol Phys. 2003;57(1):61–70. https://doi.org/10.1016/s0360-3016(03)00361-4.

    Article  PubMed  Google Scholar 

  8. Wang JJ, Goldsmith TA, Holman AS, Cianchetti M, Chan AW. Pharyngoesophageal stricture after treatment for head and neck cancer. Head Neck. 2012;34(7):967–73. https://doi.org/10.1002/hed.21842.

    Article  CAS  PubMed  Google Scholar 

  9. Zuur CL, Simis YJ, Lansdaal PE, Hart AA, Schornagel JH, Dreschler WA, Rasch CR, Balm AJ. Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer. J Clin Oncol. 2007;25(24):3759–65. https://doi.org/10.1200/jco.2006.08.9540.

    Article  CAS  PubMed  Google Scholar 

  10. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol, 42. 2015;(33, 29):3235. https://doi.org/10.1200/jco.2015.61.6995 Important paper discussing the updated epidemiological trends of HPV+ head and neck cancer.

  11. Cmelak AJ, Li S, Goldwasser MA, Murphy B, Cannon M, Pinto H, Rosenthal DI, Gillison M, Forastiere AA. Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: results of eastern cooperative oncology group study E2399. J Clin Oncol. 2007;25(25):3971–7. https://doi.org/10.1200/jco.2007.10.8951.

    Article  CAS  PubMed  Google Scholar 

  12. Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, Kim H, Silverman C, Raben A, Galloway TJ, Fortin A, Gore E, Westra WH, Chung CH, Jordan RC, Gillison ML, List M, le QT. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the radiation therapy oncology group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014;32(34):3858–66. https://doi.org/10.1200/jco.2014.55.3925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744–54. https://doi.org/10.1053/j.seminoncol.2004.09.011.

    Article  PubMed  Google Scholar 

  14. • Chen AM, Felix C, Wang PC, Hsu S, Basehart V, Garst J, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol. 2017;18(6):803–11. https://doi.org/10.1016/s1470-2045(17)30246-2 Single-arm phase II trial evaluating induction chemotherapy with carboplatin and paclitaxel followed by radiation with weekly paclitaxel.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, et al. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV+ resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol., 10.1200/jco.2016.68.3300. 2017;35(5):490–7 Cooperative group trial evaluating of induction cisplatin, paclitaxel, and cetuximab, followed by radiation with weekly cetuximab.

  16. • Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, et al. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019;30(2):297–302. https://doi.org/10.1093/annonc/mdy522The OPTIMA trial evaluating induction chemotherapy followed by risk and response-adaptive de-intensified (chemo)radiation.

    Article  CAS  PubMed  Google Scholar 

  17. • Villaflor VM, Melotek JM, Karrison TG, Brisson RJ, Blair EA, Portugal L, et al. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016;27(5):908–13. https://doi.org/10.1093/annonc/mdw051 Phase II trial investigating volume reduction and elimination of elective nodal volumes in good responders to induction.

    Article  CAS  PubMed  Google Scholar 

  18. Rosenberg AJ, Agrawal N, Pearson A, Seiwert TY, Gooi Z, Blair EA, et al. Low risk HPV associated oropharyngeal squamous cell carcinoma treated with induction chemoimmunotherapy followed by TORS or radiotherapy. Int J Rad Oncol, Biol, Phys. 2020;106(5):1123. https://doi.org/10.1016/j.ijrobp.2019.11.342.

    Article  Google Scholar 

  19. Kramer S, Gelber RD, Snow JB, Marcial VA, Lowry LD, Davis LW, Chandler R. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the radiation therapy oncology group. Head Neck Surg. 1987;10(1):19–30.

    Article  CAS  Google Scholar 

  20. Tupchong L, Scott CB, Blitzer PH, Marcial VA, Lowry LD, Jacobs JR, et al. Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys. 1991;20(1):21–8.

    Article  CAS  Google Scholar 

  21. Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991;324(24):1685–90. https://doi.org/10.1056/nejm199106133242402.

    Article  PubMed  Google Scholar 

  22. Rooney M, Kish J, Jacobs J, Kinzie J, Weaver A, Crissman J, al-Sarraf M. Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. Cancer. 1985;55(5):1123–8. https://doi.org/10.1002/1097-0142(19850301)55:5<1123::aid-cncr2820550530>3.0.co;2-8.

    Article  CAS  PubMed  Google Scholar 

  23. Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998;338(25):1798–804. https://doi.org/10.1056/nejm199806183382503.

    Article  CAS  PubMed  Google Scholar 

  24. Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845–52. https://doi.org/10.1200/jco.2012.43.6097.

    Article  CAS  PubMed  Google Scholar 

  25. Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol. 2000;18(7):1458–64. https://doi.org/10.1200/jco.2000.18.7.1458.

    Article  CAS  PubMed  Google Scholar 

  26. • Pignon JP, le Maître A, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14. https://doi.org/10.1016/j.radonc.2009.04.014 Meta-analysis demonstrating the survival benefit of chemotherapy in the definitive setting for locoregionally advanced head and neck cancer.

    Article  PubMed  Google Scholar 

  27. Pignon J-P. Maître Al, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14. https://doi.org/10.1016/j.radonc.2009.04.014.

    Article  PubMed  Google Scholar 

  28. Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, Tan M, Fasciano J, Sammartino DE, Posner MR, TAX 324 Study Group. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011;12(2):153–9. https://doi.org/10.1016/s1470-2045(10)70279-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357(17):1695–704. https://doi.org/10.1056/NEJMoa071028.

    Article  CAS  PubMed  Google Scholar 

  30. Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB, Cruz Hernandez JJ, Bourredjem A, Calais G, Paccagnella A, Hitt R, Pignon JP, Meta-Analysis of Chemotherapy in Head and Neck Cancer, Induction Project, Collaborative Group. Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013;31(23):2854–60. https://doi.org/10.1200/JCO.2012.47.7802.

    Article  CAS  PubMed  Google Scholar 

  31. • Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, et al. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014;32(25):2735–43. https://doi.org/10.1200/jco.2013.54.6309 The largest randomized phase III trial investigating the addition of induction chemotherapy to concurrent chemoradiation in locoregionally advanced head and neck cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Haddad R, O’Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, et al. 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. Lancet Oncol. 2013;14(3):257–64. https://doi.org/10.1016/s1470-2045(13)70011-1.

    Article  CAS  PubMed  Google Scholar 

  33. Hitt R, Grau JJ, López-Pousa A, Berrocal A, García-Girón C, Irigoyen A, Sastre J, Martínez-Trufero J, Brandariz Castelo JA, Verger E, Cruz-Hernández JJ, Almodóvar C, Cortés-Funes H, Escobar Y, Fonseca-Sánchez E, Galcerán JC, Guix M, Isla-Casado D, Jara-Sánchez C, et al. A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol. 2014;25(1):216–25. https://doi.org/10.1093/annonc/mdt461.

    Article  CAS  PubMed  Google Scholar 

  34. Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17(11):1509–20. https://doi.org/10.1016/s1470-2045(16)30410-7.

    Article  CAS  PubMed  Google Scholar 

  35. Yang Q, Cao SM, Guo L, Hua YJ, Huang PY, Zhang XL, Lin M, You R, Zou X, Liu YP, Xie YL, Wang ZQ, Mai HQ, Chen QY, Tang LQ, Mo HY, Cao KJ, Qian CN, Zhao C, et al. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase III multicentre randomised controlled trial. Eur J Cancer. 2019;119:87–96. https://doi.org/10.1016/j.ejca.2019.07.007.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019;381(12):1124–35. https://doi.org/10.1056/NEJMoa1905287.

    Article  CAS  PubMed  Google Scholar 

  37. Brockstein B, Haraf DJ, Rademaker AW, Kies MS, Stenson KM, Rosen F, Mittal BB, Pelzer H, Fung BB, Witt ME, Wenig B, Portugal L, Weichselbaum RW, Vokes EE. Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience. Ann Oncol. 2004;15(8):1179–86. https://doi.org/10.1093/annonc/mdh308.

    Article  CAS  PubMed  Google Scholar 

  38. Petit C, Lacas B, Pignon JP, Le QT, Grégoire V, Grau C, et al. Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis. Lancet Oncol. 2021;22(5):727–36. https://doi.org/10.1016/s1470-2045(21)00076-0.

    Article  CAS  PubMed  Google Scholar 

  39. Ensley JF, Jacobs JR, Weaver A, Kinzie J, Crissman J, Kish JA, Cummings G, al-Sarraf M. Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer. 1984;54(5):811–4. https://doi.org/10.1002/1097-0142(19840901)54:5<811::aid-cncr2820540508>3.0.co;2-e.

    Article  CAS  PubMed  Google Scholar 

  40. Hong WK, Bromer RH, Amato DA, Shapshay S, Vincent M, Vaughan C, Willett B, Katz A, Welch J, Fofonoff S, Strong MS. Patterns of relapse in locally advanced head and neck cancer patients who achieved complete remission after combined modality therapy. Cancer. 1985;56(6):1242–5. https://doi.org/10.1002/1097-0142(19850915)56:6<1242::aid-cncr2820560603>3.0.co;2-z.

    Article  CAS  PubMed  Google Scholar 

  41. Urba S, Wolf G, Eisbruch A, Worden F, Lee J, Bradford C, Teknos T, Chepeha D, Prince M, Hogikyan N, Taylor J. Single-cycle induction chemotherapy selects patients with advanced laryngeal cancer for combined chemoradiation: a new treatment paradigm. J Clin Oncol. 2006;24(4):593–8. https://doi.org/10.1200/jco.2005.01.2047.

    Article  CAS  PubMed  Google Scholar 

  42. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9. https://doi.org/10.1093/jnci/djn011.

    Article  CAS  PubMed  Google Scholar 

  43. O’Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B, et al. Deintensification candidate subgroups in human papillomavirus–related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013;31(5):543–50. https://doi.org/10.1200/jco.2012.44.0164.

    Article  PubMed  Google Scholar 

  44. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. https://doi.org/10.1056/NEJMoa0912217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. • O’Sullivan B, Huang SH, Su J, Garden AS, Sturgis EM, Dahlstrom K, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. The Lancet Oncology. 2016;17(4):440–51. https://doi.org/10.1016/s1470-2045(15)00560-4 Large, multicenter cohort study developing and validating a new staging system for HPV+ OPSCC that formed the basis of the AJCC 8th edition staging system.

    Article  PubMed  Google Scholar 

  46. Amin MB, American Joint Committee on Cancer., American Cancer Society. AJCC cancer staging manual. Eight edition / editor-in-chief, Mahul B. Amin, MD, FCAP ; editors, Stephen B. Edge, MD, FACS and 16 others ; Donna M. Gress, RHIT, CTR - Technical editor ; Laura R. Meyer, CAPM - Managing editor. ed. Chicago IL: American Joint Committee on Cancer, Springer; 2017.

  47. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, Dalby M, Mistry P, Sen M, O'Toole L, al Booz H, Dyker K, Moleron R, Whitaker S, Brennan S, Cook A, Griffin M, Aynsley E, Rolles M, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51–60. https://doi.org/10.1016/s0140-6736(18)32752-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chera BS, Amdur R, Shen CJ, Gupta GP, Tan X, Knowles M, et al. Mature results of the LCCC1413 phase II trial of de-intensified chemoradiotherapy for HPV+ oropharyngeal squamous cell carcinoma. J Clin Oncol. 2019;37(15_suppl):6022. https://doi.org/10.1200/JCO.2019.37.15_suppl.6022.

    Article  Google Scholar 

  49. Chera BS, Amdur RJ, Green R, Shen C, Gupta G, Tan X, Knowles M, Fried D, Hayes N, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Zevallos J, Blumberg J, Patel S, Kasibhatla M, Sheets N, et al. Phase II trial of de-intensified chemoradiotherapy for human papillomavirus-associated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2019;37(29):2661–9. https://doi.org/10.1200/jco.19.01007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40–50. https://doi.org/10.1016/s0140-6736(18)32779-x.

    Article  CAS  PubMed  Google Scholar 

  51. Chera BS, Amdur RJ, Tepper JE, Tan X, Weiss J, Grilley-Olson JE, Hayes DN, Zanation A, Hackman TG, Patel S, Sheets N, Weissler MC, Mendenhall WM. Mature results of a prospective study of deintensified chemoradiotherapy for low-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cancer. 2018;124(11):2347–54. https://doi.org/10.1002/cncr.31338.

    Article  CAS  PubMed  Google Scholar 

  52. Riaz N, Sherman E, Pei X, Schöder H, Grkovski M, Paudyal R, Katabi N, Selenica P, Yamaguchi TN, Ma D, Lee SK, Shah R, Kumar R, Kuo F, Ratnakumar A, Aleynick N, Brown D, Zhang Z, Hatzoglou V, et al. Precision radiotherapy: reduction in radiation for oropharyngeal cancer in the 30 ROC trial. J Natl Cancer Inst. 2021;113(6):742–51. https://doi.org/10.1093/jnci/djaa184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Holsinger FC, Ferris RL. Transoral endoscopic head and neck surgery and its role within the multidisciplinary treatment paradigm of oropharynx cancer: robotics, lasers, and clinical trials. J Clin Oncol. 2015;33(29):3285–92. https://doi.org/10.1200/jco.2015.62.3157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Nichols AC, Theurer J, Prisman E, Read N, Berthelet E, Tran E, Fung K, de Almeida JR, Bayley A, Goldstein DP, Hier M, Sultanem K, Richardson K, Mlynarek A, Krishnan S, le H, Yoo J, MacNeil SD, Winquist E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol. 2019;20(10):1349–59. https://doi.org/10.1016/s1470-2045(19)30410-3.

    Article  CAS  PubMed  Google Scholar 

  55. Ferris RL, Flamand Y, Weinstein GS, Li S, Quon H, Mehra R, et al. Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: a trial of the ECOG-ACRIN Cancer Research Group (E3311). J Clin Oncol. 2020;(38, 15_suppl):6500. https://doi.org/10.1200/JCO.2020.38.15_suppl.6500.

  56. Cmelak A, Li S, Marur S, Zhao W, Westra WH, Chung CH, et al. Symptom reduction from IMRT dose deintensification: results from ECOG 1308 using the Vanderbilt Head and Neck Symptom Survey version 2 (VHNSS V2). J Clin Oncol. 2015;33(15_suppl):6021. https://doi.org/10.1200/jco.2015.33.15_suppl.6021.

    Article  Google Scholar 

  57. Rosenberg A, Agrawal N, Pearson AT, Seiwert TY, Gooi Z, Blair EA, et al. Nivolumab, nabpaclitaxel, and carboplatin followed by risk/response adaptive de-escalated locoregional therapy for HPV+ oropharyngeal cancer: OPTIMA II trial. J Clin Oncol. 2021;39(15_suppl):6011. https://doi.org/10.1200/JCO.2021.39.15_suppl.6011.

    Article  Google Scholar 

  58. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, Dalby M, Mistry P, Sen M, O'Toole L, al Booz H, Dyker K, Moleron R, Whitaker S, Brennan S, Cook A, Griffin M, Aynsley E, Rolles M, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51–60. https://doi.org/10.1016/S0140-6736(18)32752-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Foster CC, Seiwert TY, MacCracken E, Blair EA, Agrawal N, Melotek JM, Portugal L, Brisson RJ, Gooi Z, Spiotto MT, Vokes EE, Haraf DJ. Dose and volume de-escalation for human papillomavirus-positive oropharyngeal cancer is associated with favorable posttreatment functional outcomes. Int J Radiat Oncol Biol Phys. 2020;107(4):662–71. https://doi.org/10.1016/j.ijrobp.2020.04.014.

    Article  PubMed  Google Scholar 

  60. Ma DJ, Price KA, Moore EJ, Patel SH, Hinni ML, Garcia JJ, Graner DE, Foster NR, Ginos B, Neben-Wittich M, Garces YI, Chintakuntlawar AV, Price DL, Olsen KD, van Abel KM, Kasperbauer JL, Janus JR, Waddle M, Miller R, et al. Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiotherapy in human papillomavirus–associated oropharynx squamous cell carcinoma. J Clin Oncol. 2019;37(22):1909–18. https://doi.org/10.1200/JCO.19.00463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Rosenberg AJ, Vokes EE. Optimizing treatment de-escalation in head and neck cancer: current and future perspectives. Oncologist. 2021;26(1):40–8. https://doi.org/10.1634/theoncologist.2020-0303.

    Article  PubMed  Google Scholar 

  62. Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: recent advances and future directions. Oral Oncol. 2019;99:104460. https://doi.org/10.1016/j.oraloncology.2019.104460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Galvis MM, Borges GA, Oliveira TBD, Toledo IPD, Castilho RM, Guerra ENS, et al. Immunotherapy improves efficacy and safety of patients with HPV positive and negative head and neck cancer: a systematic review and meta-analysis Crit Rev Oncol/Hematol 2020;150:102966. https://doi.org/10.1016/j.critrevonc.2020.102966.

  64. Lee NY, Ferris RL, Psyrri A, Haddad RI, Tahara M, Bourhis J, Harrington K, Chang PMH, Lin JC, Razaq MA, Teixeira MM, Lövey J, Chamois J, Rueda A, Hu C, Dunn LA, Dvorkin MV, de Beukelaer S, Pavlov D, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450–62. https://doi.org/10.1016/s1470-2045(20)30737-3.

    Article  CAS  PubMed  Google Scholar 

  65. Bourhis J, Sire C, Tao Y, Martin L, Alfonsi M, Prevost JB, et al. LBA38 Pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC): results of the GORTEC 2015-01 &#x201c;PembroRad&#x201d; randomized trial. Ann Oncol. 2020;31:S1168. https://doi.org/10.1016/j.annonc.2020.08.2268.

    Article  Google Scholar 

  66. Bourhis J, Tao Y, Sun X, Sire C, Martin L, Liem X, Coutte A, Pointreau Y, Thariat J, Miroir J, Rolland F, Kaminsky MC, Borel C, Maillard A, Sinigaglia L, Guigay J, Saada-Bouzid E, Even C, Aupérin A. Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): randomized phase III GORTEC-REACH trial. Ann Oncol. 2021;32:S1283–S346. https://doi.org/10.1016/annonc/annonc741.

    Article  Google Scholar 

  67. Schoenfeld JD, Hanna GJ, Jo VY, Rawal B, Chen YH, Catalano PS, Lako A, Ciantra Z, Weirather JL, Criscitiello S, Luoma A, Chau N, Lorch J, Kass JI, Annino D, Goguen L, Desai A, Ross B, Shah HJ, et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in untreated oral cavity squamous cell carcinoma: a phase 2 open-label randomized clinical trial. JAMA Oncol. 2020;6(10):1563–70. https://doi.org/10.1001/jamaoncol.2020.2955.

    Article  PubMed  Google Scholar 

  68. Uppaluri R, Chernock R, Mansour M, Jackson R, Rich J, Pipkorn P, et al. Enhanced pathologic tumor response with two cycles of neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2021;39(15_suppl):6008. https://doi.org/10.1200/JCO.2021.39.15_suppl.6008.

    Article  Google Scholar 

  69. Wise-Draper TM, Takiar V, Mierzwa ML, Casper K, Palackdharry S, Worden FP, et al. Association of pathological response to neoadjuvant pembrolizumab with tumor PD-L1 expression and high disease-free survival (DFS) in patients with resectable, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2021;39(15_suppl):6006. https://doi.org/10.1200/JCO.2021.39.15_suppl.6006.

    Article  Google Scholar 

  70. Sloane H, Izumchenko E, Mattox A, Hasina R, Patel A, Jones F, et al. Ultra-sensitive detection and quantification of HPV DNA in the plasma of patients with oropharyngeal squamous cell carcinoma (OPSCC) enrolled in the OPTIMA 2 treatment de-escalation trial. J Clin Oncol. 2021;39(15_suppl):6048. https://doi.org/10.1200/JCO.2021.39.15_suppl.6048.

    Article  Google Scholar 

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  1. Department of Medicine, Section of Hematology and Oncology, University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL, 60637, USA

    James M. Dolezal MD & Ari J. Rosenberg MD

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James M. Dolezal declares that he has no conflict of interest. Ari J. Rosenberg has received research funding (paid to his institution) from Bristol-Myers Squibb.

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Dolezal, J.M., Rosenberg, A.J. Induction Chemotherapy in Low-Risk HPV+ Oropharyngeal Cancer. Curr. Treat. Options in Oncol. 23, 54–67 (2022). https://doi.org/10.1007/s11864-022-00941-9

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