Laryngorhinootologie 2021; 100(10): 832-844
DOI: 10.1055/a-1523-9045
Facharztwissen HNO

Update zur Therapie des HPV-16-positiven Oropharynxkarzinoms

Update Treatment HPV-16-positive Oropharyngeal Carcinoma
Andreas Dietz
1   Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Plastische Operationen, Universität Leipzig, Leipzig, Germany
,
Gunnar Wichmann
,
Susanne Wiegand
› Author Affiliations

Das Oropharynxkarzinom stellt aufgrund seiner weltweiten Inzidenzzunahme und Assoziation mit dem humanen Papillomavirus-16, aber auch chronischem Tabak- und Alkoholkonsum eine genetisch heterogene Tumorgruppe mit hoher prognostischer Diversität dar. Die auf Basis retrospektiver Daten erstellte 8. Edition der TNM-Klassifikation und die wenigen prospektiven Daten zur Therapiedesintensivierung ermahnen aktuell eher zu einem konservativen Vorgehen.

Abstract

Background Oropharynx carcinoma (OPSCC) is a genetically heterogeneous tumor group with high prognostic diversity due to its worldwide increase in incidence and the association with the human papillomavirus HPV 16, but also chronic tobacco/alcohol consumption.

Objective The review attempts to present the current view on therapy and prevention of OPSCC with respect to association with HPV 16.

Material & Methods The overview is based on the current relevant literature as well as current studies.

Results & Discussion The OPSCC presents itself as a very complex, genetically heterogeneous group of head and neck tumors, which should therefore be considered in detail. The currently contradictory trial situation of retrospective studies versus prospective trials, the current TNM classification (8th edition) and the scarce prospective data arguing for non-inferiority of therapy de-intensification attempts currently admonish to encourage a more conservative treatment.



Publication History

Article published online:
06 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Dietz A, Pirlich M, Wiegand S. et al. Current Status of therapy and prophylaxis of oropharyngeal carcinoma]. Laryngorhinootologie 2018; 97 (02) 123-137
  • 2 Andl T, Kahn T, Pfuhl A. et al. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res 1998; 58 (01) 5-13
  • 3 Wichmann G. Variation of HPV Subtypes with Focus on HPV-Infection and Cancer in the Head and Neck Region. Recent Results Cancer Res 2017; 206: 113-122
  • 4 Wagner S, Würdemann N, Hübbers C. et al. HPV-associated head and neck cancer : mutational signature and genomic aberrations. HNO 2015; 63 (11) 758-767
  • 5 Wichmann G, Rosolowski M, Krohn K. et al. Leipzig Head and Neck Group (LHNG). The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer. Int J Cancer 2015; 137 (12) 2846-2857
  • 6 Smeets SJ, Hesselink AT, Speel EJM. et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 2007; 121: 2465-2472
  • 7 Rischin D, Young RJ, Fisher R. et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 2010; 28: 4142-4148
  • 8 Freitag J, Wald T, Kuhnt T. et al. Extracapsular extension of neck nodes and absence of human papillomavirus 16-DNA are predictors of impaired survival in p16-positive oropharyngeal squamous cell carcinoma. Cancer 2020; 126 (09) 1856-1872
  • 9 8th Edition of the UICC TNM Classification of Malignant Tumours. January 1, 2017.
  • 10 Boscolo-Rizzo P, Dietz A. The AJCC/UICC eighth edition for staging head and neck cancers: Is it wise to de-escalate treatment regimens in p16-positive oropharyngeal cancer patients?. Int J Cancer 2017; 141 (07) 1490-1491
  • 11 O'Sullivan B, Huang SH, Su J. 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. Lancet Oncol 2016; 17 (04) 440-451
  • 12 STIKO 2019 http://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Faktenblaetter/HPV.html.
  • 13 Dietz A, Fischer M, Magill C. et al. Principles and New Approaches in Surgical Reconstruction. In: Bernier J, (ed.) Head and Neck Cancer. 2. Aufl. Springer; 2016: doi:10.1007/978-3-319-27601-4_32.
  • 14 Robbins KT, Shaha AR, Medina JE. et al. Consensus statement on the classification and terminology of neck dissection. Arch Otolaryngol Head Neck Surg 2008; 134: 536-538
  • 15 Domenge C, Hill C, Lefebvre JL. et al. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC). Br J Cancer 2000; 83 (12) 1594-1598
  • 16 Licitra L, Grandi C, Guzzo M. et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 2003; 21 (02) 327-333
  • 17 Zhong LP, Zhang CP, Ren GX. et al. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol 2013; 31 (06) 744-751
  • 18 Pignon JP, Le Maitre A, Maillard E. et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NH): An update on 93 randomised trials and 17346 patients. Radiother Oncol 2009; 92: 4-14
  • 19 Budach W, Hehr T, Budach V. et al. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer 2006; 6: 28
  • 20 Ang KK, Harris J, Wheeler R. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363 (01) 24-35
  • 21 Haughey BH, Hinni ML, Salassa JR. et al. Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a United States multicenter study. Head Neck 2011; 33 (12) 1683-1694
  • 22 Sinha P, Lewis JS, Piccirillo JF. et al. Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma. Cancer 2012; 118 (14) 3519-3530
  • 23 Weinstein GS, O’Malley BW, Magnuson JS. et al. Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins. Laryngoscope 2012; 122 (08) 1701-1707
  • 24 Mattheis S, Hasskamp P, Holtmann L. et al. Flex Robotic System in transoral robotic surgery: The first 40 patients. Head Neck 2017; 39 (03) 471-475
  • 25 Adelstein DJ, Ridge JA, Gillison ML. et al. Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head Neck 2009; 31: 1393-1422
  • 26 Cramer JD, Ferris RL, Duvvuri U. Treatment deintensification to surgery only for stage I human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2018; 36 (Suppl. 15)
  • 27 Langer C, Wittekindt C, Jensen AD. The role of chemoradiotherapy in curative treatment of head and neck cancer. Laryngorhinootologie 27.01.2021;
  • 28 Nichols AC, Theurer J, Prisman 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) 1349-1359
  • 29 PRESSEMITTEILUNG DEGRO. 24. Januar 2020; Mund-Rachen-Krebs: Radiotherapie führt zu weniger Schluckstörungen als die Roboter-gesteuerte OP..
  • 30 O'Sullivan B, Huang SH, Siu LL. et al. Deintensification Candidate Subgroups in Human Papillomavirus-Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis. J Clin Oncol 2013; 31 (05) 543-550
  • 31 Brotherston DC, Poon I, Le T. et al. Patient preferences for oropharyngeal cancer treatment de-escalation. Head Neck 2013; 35 (02) 151-159
  • 32 Mehanna H, Kong A, Hartley A. et al. Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy. Ann Oncol 2018; 29 (Suppl. 08)
  • 33 Gillison ML, Trotti AM, Harris J. 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: 40-50
  • 34 Yom SS, Torres-Saavedra P, Caudell JJ. et al. Reduced-dose radiation therapy for HPV-associated oropharyngeal carcinoma (NRG Oncology HN002). J Clin Oncol 2021;
  • 35 Inhestern J, Schmalenberg H, Dietz A. et al. A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol 2017; 28 (08) 1917-1922
  • 36 Wichmann G, Krüger A, Boehm A. et al. Induction chemotherapy followed by radiotherapy for larynx preservation in advanced laryngeal and hypopharyngeal cancer: Outcome prediction after one cycle induction chemotherapy by a score based on clinical evaluation, computed tomography-based volumetry and 18F-FDG-PET/CT. Eur J Cancer 2017; 72: 144-155
  • 37 Dietz A, Wichmann G, Kuhnt T. et al. Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. Ann Oncol 2018; 29 (10) 2105-2114
  • 38 Seiwert TY, Foster CC, Blair EA. et al. OPTIMA: A phase II dose and volume de- escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol 2019; 30: 297-302
  • 39 Rosenberg A, Vokes EE. Optimizing Treatment De-Escalation in Head and Neck Cancer: Current and Future Perspectives. The Oncologist 2021; 26: 40-48
  • 40 National Cancer Institute. The Quarterback Trial. Bethesda, MD, USA: National Cancer Institute.. 2012
  • 41 Fakhry C, Zhang Q, Nguyen-Tan PF. et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol 2014; 32 (30) 3365-3373
  • 42 Goodwin WJ. Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means?. Laryngoscope 2000; 110 (Suppl. 93) 1-18
  • 43 Dietz A, Stöhr M, Zebralla V. et al. Immuno oncology treatment in head and neck cancer. Laryngorhinootologie 2021; 100 (04) 303-321