Advertisement

Postoperative Treatment of Oropharyngeal Cancer in the Era of Human Papillomavirus

  • Jessica L. GeigerEmail author
  • Jamie A. Ku
Head and Neck Cancer (CP Rodriguez, Section Editor)
  • 231 Downloads
Part of the following topical collections:
  1. Topical Collection on Head and Neck Cancer

Opinion statement

Despite an overall decline in the incidence of tobacco-related cancers, human papillomavirus (HPV)–related head and neck squamous cell carcinoma (HNSCC) of the oropharynx is on the rise. The prognosis of HPV-related oropharynx cancer (HPV-OPC) is generally favorable even in locoregionally advanced disease, and a variety of treatment options are available. Though the primary treatment modality of choice remains definitive radiation (RT), surgical resection followed by appropriate adjuvant therapy remains an option, especially in those patients who may not be favorable candidates for definitive radiotherapy, particularly when concurrent chemotherapy is warranted. Upfront resection may offer a chance to avoid the well-described acute toxicity and long-term morbidity associated with concurrent chemoradiotherapy (CRT) in select patients. Despite the overall favorable prognosis of HPV-OPC, indications for therapy remain unchanged from the recommendations for treatment in tobacco-related OPC and other anatomic sites of HNSCC. Ongoing studies assessing deintensification strategies in HPV-OPC are focused on maintaining high cure rates while improving treatment-related toxicities. Currently, no clear guidelines exist for the choice of primary therapy, surgical resection, or RT in patients with HPV-OPC, highlighting the need for multidisciplinary discussion and review of the individual patient before selecting the most appropriate curative modality. This review seeks to present the data for postoperative therapy in HPV-related oropharyngeal HNSCC.

Keywords

Head and neck cancer Oropharyngeal cancer Human papillomavirus Squamous cell carcinoma of the head and neck 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

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

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(32):4294–301.CrossRefGoogle Scholar
  4. 4.
    Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer–systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, et al. Annual report to the nation on the status of cancer, 1975–2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013;105(3):175–201.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Stein AP, Saha S, Kraninger JL, Swick AD, Yu M, Lambert PF, et al. Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. Cancer J. 2015;21(3):138–46.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol. 2010;2:15.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    •• Lydiatt WM, Patel SG, O’Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, et al. Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122–37. New staging system guidelines with pertinent changes for HPV-related disease.PubMedCrossRefGoogle Scholar
  9. 9.
    Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007;121(8):1813–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Nichols AC, Faquin WC, Westra WH, Mroz EA, Begum S, Clark JR, et al. HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009;140(2):228–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Hafkamp HC, Manni JJ, Haesevoets A, Voogd AC, Schepers M, Bot FJ, et al. Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer. 2008;122(12):2656–64.PubMedCrossRefGoogle Scholar
  13. 13.
    Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2006;24(36):5630–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(30):3365–73.CrossRefGoogle Scholar
  15. 15.
    Deeken JF, Newkirk K, Harter KW, Marshall MB, Banovac F, Johnson L, et al. Effect of multimodality treatment on overall survival for patients with metastatic or recurrent HPV-positive head and neck squamous cell carcinoma. Head Neck. 2015;37(5):630–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Kramer S, Gelber RD, Snow JB, Marcial VA, Lowry LD, Davis LW, et al. 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Fletcher GH, Evers WT. Radiotherapeutic management of surgical recurrences and postoperative residuals in tumors of the head and neck. Radiology. 1970;95(1):185–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Snow GB, Annyas AA, van Slooten EA, Bartelink H, Hart AA. Prognostic factors of neck node metastasis. Clin Otolaryngol Allied Sci. 1982;7(3):185–92.PubMedCrossRefGoogle Scholar
  19. 19.
    Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy. Cancer. 2005;104(7):1408–17.PubMedCrossRefGoogle Scholar
  20. 20.
    Bastit L, Blot E, Debourdeau P, Menard J, Bastit P, Le Fur R. Influence of the delay of adjuvant postoperative radiation therapy on relapse and survival in oropharyngeal and hypopharyngeal cancers. Int J Radiat Oncol Biol Phys. 2001;49(1):139–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Peters LJ, Goepfert H, Ang KK, Byers RM, Maor MH, Guillamondegui O, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys. 1993;26(1):3–11.PubMedCrossRefGoogle Scholar
  22. 22.
    Sanguineti G, Richetti A, Bignardi M, Corvo R, Gabriele P, Sormani MP, et al. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter phase III study. Int J Radiat Oncol Biol Phys. 2005;61(3):762–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Suwinski R, Bankowska-Wozniak M, Majewski W, Idasiak A, Maciejewski A, Ziolkowska E, et al. Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high-risk squamous cell head and neck cancer. Radiother Oncol. 2008;87(2):155–63.PubMedCrossRefGoogle Scholar
  24. 24.
    Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–52.PubMedCrossRefGoogle Scholar
  26. 26.
    Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27(10):843–50.CrossRefPubMedGoogle Scholar
  27. 27.
    Guan J, Zhang Y, Li Q, Zhang Y, Li L, Chen M, et al. A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC). Oncotarget. 2016;7(43):70185–93.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996;36(5):999–1004.PubMedCrossRefGoogle Scholar
  29. 29.
    Szturz P, Wouters K, Kiyota N, Tahara M, Prabhash K, Noronha V, et al. Weekly low-dose versus three-weekly high-dose cisplatin for concurrent chemoradiation in locoregionally advanced non-nasopharyngeal head and neck cancer: a systematic review and meta-analysis of aggregate data. Oncologist. 2017;22(9):1056–66.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Smid L, Budihna M, Zakotnik B, Soba E, Strojan P, Fajdiga I, et al. Postoperative concomitant irradiation and chemotherapy with mitomycin C and bleomycin for advanced head-and-neck carcinoma. Int J Radiat Oncol Biol Phys. 2003;56(4):1055–62.PubMedCrossRefGoogle Scholar
  31. 31.
    Racadot S, Mercier M, Dussart S, Dessard-Diana B, Bensadoun RJ, Martin M, et al. Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. Radiother Oncol. 2008;87(2):164–72.PubMedCrossRefGoogle Scholar
  32. 32.
    Argiris A, Karamouzis MV, Johnson JT, Heron DE, Myers E, Eibling D, et al. Long-term results of a phase III randomized trial of postoperative radiotherapy with or without carboplatin in patients with high-risk head and neck cancer. Laryngoscope. 2008;118(3):444–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Mesia R, Rueda A, Vera R, Lozano A, Medina JA, Aguiar D, et al. Adjuvant therapy with cetuximab for locally advanced squamous cell carcinoma of the oropharynx: results from a randomized, phase II prospective trial. Ann Oncol. 2013;24(2):448–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: a phase III randomized noninferiority trial. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(11):1064–72.CrossRefGoogle Scholar
  35. 35.
    Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, et al. 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. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22(1):69–76.CrossRefGoogle Scholar
  36. 36.
    Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21(1):92–8.CrossRefGoogle Scholar
  37. 37.
    Trotti A, Pajak TF, Gwede CK, Paulus R, Cooper J, Forastiere A, et al. TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. Lancet Oncol. 2007;8(7):613–24.PubMedCrossRefGoogle Scholar
  38. 38.
    Bossi P, Cossu Rocca M, Corvo R, Depenni R, Guardamagna V, Marinangeli F, et al. The vicious circle of treatment-induced toxicities in locally advanced head and neck cancer and the impact on treatment intensity. Crit Rev Oncol Hematol. 2017;116:82–8.PubMedCrossRefGoogle Scholar
  39. 39.
    van der Laan HP, Bijl HP, Steenbakkers RJ, van der Schaaf A, Chouvalova O, Vemer-van den Hoek JG, et al. Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia. Radiother Oncol. 2015;115(1):56–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Mortensen HR, Jensen K, Aksglaede K, Behrens M, Grau C. Late dysphagia after IMRT for head and neck cancer and correlation with dose-volume parameters. Radiother Oncol. 2013;107(3):288–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Frowen J, Hornby C, Collins M, Senthi S, Cassumbhoy R, Corry J. Reducing posttreatment dysphagia: support for the relationship between radiation dose to the pharyngeal constrictors and swallowing outcomes. Pract Radiat Oncol. 2013;3(4):e187–94.PubMedCrossRefGoogle Scholar
  42. 42.
    Vlacich G, Spratt DE, Diaz R, Phillips JG, Crass J, Li CI, et al. Dose to the inferior pharyngeal constrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer. Radiother Oncol. 2014;110(3):435–40.PubMedCrossRefGoogle Scholar
  43. 43.
    • 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-associated resectable squamous cell carcinoma of the oropharynx—ECOG-ACRIN Cancer Research Group. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(5):490–7 Large clinical study first reported looking at deintensifying treatment for HPV-OPC.CrossRefGoogle Scholar
  44. 44.
    Ma D. Two year results for MC1273, a phase II evaluation of aggressive dose de-escalation for adjuvant chenoradiation in HPV+ oropharynx squamous cell carcinomas (OPSCC) ASTRO 2017; Abstract LBA-14.Google Scholar
  45. 45.
    Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, 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. 2018.Google Scholar
  46. 46.
    Liederbach E, Lewis CM, Yao K, Brockstein BE, Wang CH, Lutfi W, et al. A contemporary analysis of surgical trends in the treatment of squamous cell carcinoma of the oropharynx from 1998 to 2012: a report from the National Cancer Database. Ann Surg Oncol. 2015;22(13):4422–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Chen MM, Roman SA, Kraus DH, Sosa JA, Judson BL. Transoral robotic surgery: a population-level analysis. Otolaryngol Head Neck Surg. 2014;150(6):968–75.PubMedCrossRefGoogle Scholar
  48. 48.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Dowthwaite SA, Franklin JH, Palma DA, Fung K, Yoo J, Nichols AC. The role of transoral robotic surgery in the management of oropharyngeal cancer: a review of the literature. ISRN Oncol. 2012;2012:945162.PubMedPubMedCentralGoogle Scholar
  50. 50.
    de Almeida JR, Li R, Magnuson JS, Smith RV, Moore E, Lawson G, et al. Oncologic outcomes after transoral robotic surgery: a multi-institutional study. JAMA Otolaryngol Head Neck Surg. 2015;141(12):1043–51.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Kelly JR, Park HS, An Y, Yarbrough WG, Contessa JN, Decker R, et al. Upfront surgery versus definitive chemoradiotherapy in patients with human papillomavirus-associated oropharyngeal squamous cell cancer. Oral Oncol. 2018;79:64–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Sinha P, Lewis JS Jr, Piccirillo JF, Kallogjeri D, Haughey BH. Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma. Cancer. 2012;118(14):3519–30.PubMedCrossRefGoogle Scholar
  53. 53.
    Maxwell JH, Ferris RL, Gooding W, Cunningham D, Mehta V, Kim S, et al. Extracapsular spread in head and neck carcinoma: impact of site and human papillomavirus status. Cancer. 2013;119(18):3302–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Lewis JS Jr, Tarabishy Y, Luo J, Mani H, Bishop JA, Leon ME, et al. Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases. Oral Oncol. 2015;51(11):985–90.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Sinha P, Pipkorn P, Thorstad WL, Gay HA, Haughey BH. Does elimination of planned postoperative radiation to the primary bed in p16-positive, transorally-resected oropharyngeal carcinoma associate with poorer outcomes? Oral Oncol. 2016;61:127–34.PubMedCrossRefGoogle Scholar
  56. 56.
    Lazarev S, Todorov B, Tam J, Gupta V, Miles BA, Lee N, et al. Adjuvant radiation in the TORS era: is there a benefit to omitting the tumor bed? Pract Radiat Oncol. 2017;7(2):93–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Fried D, Lehman-Davis M, Willson A, Kostich M, Hackman T, Lian J, et al. Dosimetric feasibility of sparing the primary site for oropharyngeal squamous cell carcinoma after transoral laser microsurgery in patients with unilateral positive neck nodes. Pract Radiat Oncol. 2013;3(4):282–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Hematology and Medical Oncology, Taussig Cancer InstituteCleveland ClinicClevelandUSA
  2. 2.Department of Head and Neck Oncologic Surgery, Head and Neck InstituteCleveland ClinicClevelandUSA
  3. 3.Department of Facial Plastic & Microvascular Surgery, Head and Neck InstituteCleveland ClinicClevelandUSA

Personalised recommendations