Das multizentrische Register „Oropharynxkarzinom“ des Deutschen Studienzentrums für HNO – erste Ergebnisse

Zusammenfassung

Hintergrund Die Zahl der durch humane Papillomaviren (HPV) verursachten oropharyngealen Plattenepithelkarzinome (OPSCC) hat in den letzten Jahrzehnten deutlich zugenommen. Es gibt bislang jedoch keine belastbaren Daten über die Häufigkeit von HPV-assoziiertem OPSCC in Mitteleuropa und dessen Behandlung.

Ziel der Arbeit Die epidemiologische Erfassung von Patienten mit OPSCC und des Anteils der p16-positiven Tumoren in der Deutschen Krebsgesellschaft (DKG) zertifizierten Kopf-Hals-Tumorzentren.

Material und Methoden Um die Evidenzlücke der Häufigkeit von p16-positiven OPSCC zu schließen, wurde ein multizentrisches Register eingerichtet, das Patienten mit OPSCC im deutschsprachigen Raum pseudonymisiert erfasst. Die Datenerfassung erfolgt prospektiv mit Research Electronic Data Capture (REDCap).

Ergebnisse Insgesamt wurden in den Jahren 2022–2023 1312 Patienten mit einem OPSCC aus 34 Zentren eingeschlossen. Bei 720 Patienten (58,2 %) konnte p16 im Tumor nachgewiesen werden. Die häufigsten Lokalisationen der p16-positiven OPSCC waren mit 49,9 % die Tonsille und mit 28,7 % der Zungengrund. 63,1 % der p16-positiven OPSCC wurden primär chirurgisch behandelt, wohingegen nur 48,0 % der p16-negativen Tumoren primär operiert wurden. Bei der adjuvanten Therapie von OPSCC zeigen sich ebenfalls deutliche Unterschiede: 58 % der p16-negativen OPSCC erhielten keine adjuvante Therapie nach Operation, verglichen mit nur 37,1 % der p16-positiven OPSCC.

Schlussfolgerung Der Start der Oropharynx-Registerstudie verlief reibungslos. Dieses Register gibt bereits jetzt einen Einblick in die aktuelle Versorgungssituation von OPSCC im deutschsprachigen Raum und wird durch die Teilnahme weiterer Zentren an Bedeutung gewinnen.

Abstract

Background The number of oropharyngeal squamous cell carcinomas (OPSCC) caused by human papillomavirus (HPV) has increased significantly in recent years. However, no robust data exist on the incidence of HPV-associated OPSCC as well as their treatment in central Europe.

Aim of the work The aim is to establish an epidemiological register of patients with OPSCC in central Europe.

Material and Methods To close the evidence gap on p16-positive OPSCC, a prospective multicenter registry on incidence, risk factors and treatment of OPSCC in certified Head and Neck Tumor Centers according to the German Cancer Society was established. Data collection was pseudonymously performed using the web-based Research Electronic Data Capture (REDCap).

Results In 2022 and 2023, 1312 patients with OPSCC from 34 centers were included. 720 patients (58.2 %) were p16-positive. The most common locations of p16-positive primary tumors were the tonsil (49.9 %) and the base of the tongue (28.7 %). 63.1 % of p16-positive OPSCC received primary surgical treatment, whereas only 48.0 % of p16-negative tumors received primary surgery. Differences are also evident in the adjuvant therapy: 58 % of p16-negative OPSCC did not receive adjuvant therapy after surgery, compared with 37.1 % of p16-positive OPSCC.

Conclusion The start of the OPSCC registry study was technically smooth. This registry provides an insight into the current care situation of OPSCC in German-speaking countries and will gain importance through the participation of more centers.

Schlüsselwörter

HPV - p16 - Registerstudie - OPSCC - Plattenepithelkarzinom - Oropharynxkarzinom

Keywords

oropharyngeal carcinoma - HPV - OSCC

^* Dirk Beutner und Nicholas Bevis teilen sich die Erstautorenschaft.

Publication History

Received: 09 July 2024

Accepted: 24 July 2024

Article published online:
21 August 2024

• Literatur

• 1 Wittekindt C, Wagner S, Sharma SJ. et al. HPV – Das andere Kopf-Hals-Karzinom. Laryngorhinootologie 2018; 97: S48-S113
• 2 Zamani M, Grønhøj C, Jensen DH. et al. The current epidemic of HPV-associated oropharyngeal cancer: An 18-year Danish population-based study with 2,169 patients. Eur J Cancer 2020; 134: 52-59
• 3 Wittekindt C, Wagner S, Bushnak A. et al. Increasing Incidence rates of Oropharyngeal Squamous Cell Carcinoma in Germany and Significance of Disease Burden Attributed to Human Papillomavirus. Cancer Prev Res (Phila) 2019; 12: 375-382
• 4 Tinhofer I, Jöhrens K, Keilholz U. et al. Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence. Eur J Cancer 2015; 51: 514-521
• 5 D'Souza G, Westra WH, Wang SJ. et al. Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method. JAMA Oncol 2017; 3: 169-177
• 6 STIKO. Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut/Stand: August 2014. Robert Koch-Institut, Infektionsepidemiologie 2014;
• 7 Gross GE, Werner RN, Avila Valle GL. et al. German evidence and consensus-based (S3) guideline: Vaccination recommendations for the prevention of HPV-associated lesions. J Dtsch Dermatol Ges 2021; 19 (03) 479-494
• 8 Epid Bull 2024; 4: 1-72
• 9 Nielsen KJ, Jakobsen KK, Jensen JS. et al. The Effect of Prophylactic HPV Vaccines on Oral and Oropharyngeal HPV Infection-A Systematic Review. Viruses 2021; 13
• 10 Zhang Y, Fakhry C, D'Souza G. Projected Association of Human Papillomavirus Vaccination With Oropharynx Cancer Incidence in the US, 2020-2045. JAMA Oncol 2021; 7: e212907
• 11 Klussmann JP, Weissenborn SJ, Wieland U. et al. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 2001; 92: 2875-2884
• 12 Westra WH, Lewis JS. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx. Head Neck Pathol 2017; 11: 41-47
• 13 Klussmann JP, Gültekin E, Weissenborn SJ. et al. Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol 2003; 162: 747-753
• 14 Wagner S, Prigge E-S, Wuerdemann N. et al. Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation. Br J Cancer 2020; 123: 1114-1122
• 15 Mehanna H, Taberna M, von Buchwald C . et al. Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. Lancet Oncol 2023; 24: 239-251
• 16 Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol 2012; 6 (Suppl. 01) S16-S24
• 17 Wagner S, Wittekindt C, Sharma SJ. et al. Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer. Br J Cancer 2017; 116: 1604-1611
• 18 Sinha P, Karadaghy OA, Doering MM. et al. Survival for HPV-positive oropharyngeal squamous cell carcinoma with surgical versus non-surgical treatment approach: A systematic review and meta-analysis. Oral Oncol 2018; 86: 121-131
• 19 Zimmermann PH, Stuut M, Wuerdemann N. et al. Upfront Surgery vs. Primary Chemoradiation in an Unselected, Bicentric Patient Cohort with Oropharyngeal Squamous Cell Carcinoma-A Matched-Pair Analysis. Cancers (Basel) 2021; 13
• 20 Ang KK, Harris J, Wheeler R. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363: 24-35
• 21 Dietz A, Wichmann G, Wiegand S. et al. Update: Epidemiologie und Prävention des Oropharynxkarzinoms. Laryngorhinootologie 2024; 103: 296-313
• 22 Reuschenbach M, Tinhofer I, Wittekindt C. et al. A systematic review of the HPV-attributable fraction of oropharyngeal squamous cell carcinomas in Germany. Cancer Med 2019; 8: 1908-1918
• 23 Brierley JD. TNM Classification of Malignant Tumours. 8th ed. Chicester: John Wiley & Sons Incorporated; 2017
• 24 Kouka M, Gerlach L, Büntzel J. et al. Impact of Human Papillomavirus-Negative Dominance in Oropharyngeal Cancer on Overall Survival: A Population-Based Analysis in Germany from 2018 to 2020. Cancers (Basel) 2023; 15
• 25 Wuerdemann N, Doescher J, Laban S. et al. Humane Papillomaviren und das Oropharynxkarzinom. Onkologe 2019; 25: 224-231
• 26 Ma C, Xi B, Li Z. et al. Prevalence and trends in tobacco use among adolescents aged 13-15 years in 143 countries, 1999-2018: findings from the Global Youth Tobacco Surveys. Lancet Child Adolesc Health 2021; 5: 245-255
• 27 Johannsen J, Würdemann N, Wolber P, Klußmann JP. Der Inzidenztrend des HPV-assoziierten Oropharynxkarzinoms im Zeitraum 2004–2020 in Köln. In: Abstract- und Posterband – 93. Jahresversammlung der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie e.V., Bonn Interface – Fokus Mensch im Zeitalter der technisierten Medizin. Laryngo-Rhino-Otologie. Georg Thieme Verlag; 2022.
• 28 Klasen C, Wuerdemann N, Rothbart P. et al. Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study. BMC Cancer 2023; 23: 1054
• 29 Li H, Park HS, Osborn HA. et al. Sex differences in patients with high risk HPV-associated and HPV negative oropharyngeal and oral cavity squamous cell carcinomas. Cancers Head Neck 2018; 3: 4
• 30 Wittekindt C, Klussmann JP. Tumor Staging and HPV-Related Oropharyngeal Cancer. Recent Results Cancer Res 2017; 206: 123-133
• 31 Sharma SJ, Wagner S, Reder HSF. et al. The 8th edition AJCC/UICC TNM staging for p16-positive oropharyngeal carcinoma: is there space for improvement?. Eur Arch Otorhinolaryngol 2018; 275: 3087-3091
• 32 Wagner S, Prigge E-S, Wuerdemann N. et al. Correction: Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation. Br J Cancer 2021; 125: 307
• 33 Marklund L, Holzhauser S, de Flon C . et al. Survival of patients with oropharyngeal squamous cell carcinomas (OPSCC) in relation to TNM 8 – Risk of incorrect downstaging of HPV-mediated non-tonsillar, non-base of tongue carcinomas. Eur J Cancer 2020; 139: 192-200
• 34 Shinn JR, Davis SJ, Lang-Kuhs KA. et al. Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort. Am J Surg Pathol 2021; 45: 951-961
• 35 Carlander AF, Jakobsen KK, Bendtsen SK. et al. A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide. Viruses 2021; 13
• 36 Gillison ML, Chaturvedi AK, Anderson WF. et al. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol 2015; 33 (29) 3235-3242