Skip to main content
Erschienen in: Annals of Surgical Oncology 13/2015

01.12.2015 | Head and Neck Oncology

Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer

verfasst von: N. Gopalakrishna Iyer, MD, PhD, Snjezana Dogan, MD, Frank Palmer, BA, Rahmatullah Rahmati, MD, Iain J. Nixon, MD, Nancy Lee, MD, Snehal G. Patel, MD, Jatin P. Shah, MD, Ian Ganly, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 13/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

Oropharyngeal cancers (OPC) secondary to human papillomavirus (HPV) infections likely represent a completely different disease compared with conventional head and neck cancers. Our objective was to analyze a surgically treated cohort to determine predictors of outcome in HPV-positive versus HPV-negative patients.

Methods

HPV positivity was inferred based on p16-immunohistochemistry. Data was available for 201 patients with OPC treated with surgical resection with/without adjuvant radiotherapy between 1985 and 2005. Subsite distribution was: 66 (33 %) tonsil, 46 (23 %) soft palate, and 89 (44 %) tongue base. Patients were classified into low-, intermediate-, and high-risk groups based on p16 status and smoking history. Outcomes stratified by p16 status and risk groups were determined by the Kaplan–Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses.

Results

In this cohort, 30 % had locally advanced disease (pT3/T4) and 71 % had nodal metastasis. The 5-year overall (OS), disease-specific, and recurrence-free survival rates were 60, 76, and 66 %, respectively. There were 22 % low-, 34 % intermediate-, and 44 % high-risk patients. Patients who were p16-positive had better survival compared with p16-negative (OS, 74 vs. 44 %; p < .001). Similarly, low-risk group patients had a better survival compared with intermediate- and high-risk groups (OS, 76, 68, 45 %, respectively, p < .001). Independent predictors of survival in p16-negative patients included margin status, lymphovascular invasion, pN status, and extracapsular spread. In contrast, none of these were predictive in p16-positive patients.

Conclusions

Surgically treated patients with p16-positive OPC have superior survival compared with p16-negative patients. Outcomes in p16-positive and p16-negative OPC are determined by different prognostic factors supporting the notion that these are very different diseases. These should be incorporated into future clinical trials design.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467–75.CrossRefPubMed Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467–75.CrossRefPubMed
2.
Zurück zum Zitat Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol. 2006;24:2606–11.CrossRefPubMed Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol. 2006;24:2606–11.CrossRefPubMed
3.
Zurück zum Zitat Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110:1429–35.CrossRefPubMed Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110:1429–35.CrossRefPubMed
4.
Zurück zum Zitat Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.CrossRefPubMed Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.CrossRefPubMed
5.
6.
Zurück zum Zitat Hong AM, Dobbins TA, Lee CS, et al. Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 2010;103:1510–7.PubMedCentralCrossRefPubMed Hong AM, Dobbins TA, Lee CS, et al. Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 2010;103:1510–7.PubMedCentralCrossRefPubMed
7.
Zurück zum Zitat Parsons JT, Mendenhall WM, Stringer SP, et al. Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both. Cancer. 2002;94:2967–80.CrossRefPubMed Parsons JT, Mendenhall WM, Stringer SP, et al. Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both. Cancer. 2002;94:2967–80.CrossRefPubMed
8.
Zurück zum Zitat Lee NY, de Arruda FF, Puri DR, et al. A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;66:966–74.CrossRefPubMed Lee NY, de Arruda FF, Puri DR, et al. A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;66:966–74.CrossRefPubMed
9.
Zurück zum Zitat Pernot M, Luporsi E, Hoffstetter S, et al. Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients). Int J Radiat Oncol Biol Phys. 1997;37:577–85.CrossRefPubMed Pernot M, Luporsi E, Hoffstetter S, et al. Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients). Int J Radiat Oncol Biol Phys. 1997;37:577–85.CrossRefPubMed
10.
Zurück zum Zitat Sturgis EM, Ang KK. The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms? J Natl Compr Cancer Netw. 2011;9:665–73. Sturgis EM, Ang KK. The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms? J Natl Compr Cancer Netw. 2011;9:665–73.
11.
Zurück zum Zitat Laccourreye O, Hans S, Menard M, Garcia D, Brasnu D, Holsinger FC. Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: II. An analysis of the incidence, related variables, and consequences of local recurrence. Arch Otolaryngol Head Neck Surg. 2005;131:592–9.CrossRefPubMed Laccourreye O, Hans S, Menard M, Garcia D, Brasnu D, Holsinger FC. Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: II. An analysis of the incidence, related variables, and consequences of local recurrence. Arch Otolaryngol Head Neck Surg. 2005;131:592–9.CrossRefPubMed
12.
Zurück zum Zitat Holsinger FC, McWhorter AJ, Menard M, Garcia D, Laccourreye O. Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: I. Technique, complications, and functional results. Arch Otolaryngol Head Neck Surg. 2005;131:583–91.CrossRefPubMed Holsinger FC, McWhorter AJ, Menard M, Garcia D, Laccourreye O. Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: I. Technique, complications, and functional results. Arch Otolaryngol Head Neck Surg. 2005;131:583–91.CrossRefPubMed
13.
Zurück zum Zitat Grant DG, Salassa JR, Hinni ML, Pearson BW, Perry WC. Carcinoma of the tongue base treated by transoral laser microsurgery, part one: Untreated tumors, a prospective analysis of oncologic and functional outcomes. Laryngoscope. 2006;116:2150–5.CrossRefPubMed Grant DG, Salassa JR, Hinni ML, Pearson BW, Perry WC. Carcinoma of the tongue base treated by transoral laser microsurgery, part one: Untreated tumors, a prospective analysis of oncologic and functional outcomes. Laryngoscope. 2006;116:2150–5.CrossRefPubMed
14.
Zurück zum Zitat O’Malley BW, Jr., Weinstein GS, Snyder W, Hockstein NG. Transoral robotic surgery (TORS) for base of tongue neoplasms. Laryngoscope. 2006;116:1465–72.CrossRefPubMed O’Malley BW, Jr., Weinstein GS, Snyder W, Hockstein NG. Transoral robotic surgery (TORS) for base of tongue neoplasms. Laryngoscope. 2006;116:1465–72.CrossRefPubMed
15.
Zurück zum Zitat Weinstein GS, O’Malley BW, Jr., Snyder W, Sherman E, Quon H. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg. 2007;133:1220–6.CrossRefPubMed Weinstein GS, O’Malley BW, Jr., Snyder W, Sherman E, Quon H. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg. 2007;133:1220–6.CrossRefPubMed
16.
Zurück zum Zitat Iyer NG, Kim L, Nixon IJ, Palmer F, Shah JP, Patel SG, Ganly I. Outcome of patients with early T1 and T2 squamous cell carcinoma of the base of tongue managed by conventional surgery with adjuvant postoperative radiation. Head Neck. 2013;35:999–1006.CrossRefPubMed Iyer NG, Kim L, Nixon IJ, Palmer F, Shah JP, Patel SG, Ganly I. Outcome of patients with early T1 and T2 squamous cell carcinoma of the base of tongue managed by conventional surgery with adjuvant postoperative radiation. Head Neck. 2013;35:999–1006.CrossRefPubMed
17.
Zurück zum Zitat Iyer NG, Nixon IJ, Palmer F, et al. Surgical management of squamous cell carcinoma of the soft palate: factors predictive of outcome. Head Neck. 2012;34:1071–80.CrossRefPubMed Iyer NG, Nixon IJ, Palmer F, et al. Surgical management of squamous cell carcinoma of the soft palate: factors predictive of outcome. Head Neck. 2012;34:1071–80.CrossRefPubMed
18.
Zurück zum Zitat Kumar B, Cordell KG, Lee JS, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008;26:3128–37.PubMedCentralCrossRefPubMed Kumar B, Cordell KG, Lee JS, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008;26:3128–37.PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Fakhry C, Westra WH, Li S, 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;100:261–9.CrossRefPubMed Fakhry C, Westra WH, Li S, 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;100:261–9.CrossRefPubMed
20.
Zurück zum Zitat Nasman A, Attner P, Hammarstedt L, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125:362–6.CrossRefPubMed Nasman A, Attner P, Hammarstedt L, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125:362–6.CrossRefPubMed
21.
Zurück zum Zitat Nasman A, Nordfors C, Holzhauser S, et al. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: A stabilisation of an epidemic of viral induced carcinoma? Eur J Cancer. 2015;51:55–61.CrossRefPubMed Nasman A, Nordfors C, Holzhauser S, et al. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: A stabilisation of an epidemic of viral induced carcinoma? Eur J Cancer. 2015;51:55–61.CrossRefPubMed
22.
Zurück zum Zitat D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New Engl J Med. 2007;356:1944–56.CrossRefPubMed D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New Engl J Med. 2007;356:1944–56.CrossRefPubMed
23.
Zurück zum Zitat Mitchell D, Audisio R, Cruickshank G, et al. Boys in the UK should be offered vaccination against human papillomavirus (HPV). BMJ. 2014;348:g3762.CrossRefPubMed Mitchell D, Audisio R, Cruickshank G, et al. Boys in the UK should be offered vaccination against human papillomavirus (HPV). BMJ. 2014;348:g3762.CrossRefPubMed
24.
Zurück zum Zitat 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;33:1683–94.CrossRefPubMed 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;33:1683–94.CrossRefPubMed
25.
Zurück zum Zitat Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p16 + oropharyngeal cancer. Laryngoscope. 2012;122 Suppl 2:S13–33.CrossRefPubMed Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p16 + oropharyngeal cancer. Laryngoscope. 2012;122 Suppl 2:S13–33.CrossRefPubMed
26.
Zurück zum Zitat Setton J, Caria N, Romanyshyn J, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial Sloan-Kettering Cancer Center experience. Int J Radiat Oncol Biol Phys. 2012;82:291–8.CrossRefPubMed Setton J, Caria N, Romanyshyn J, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial Sloan-Kettering Cancer Center experience. Int J Radiat Oncol Biol Phys. 2012;82:291–8.CrossRefPubMed
27.
Zurück zum Zitat Garden AS, Dong L, Morrison WH, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:941–7.CrossRefPubMed Garden AS, Dong L, Morrison WH, et al. Patterns of disease recurrence following treatment of oropharyngeal cancer with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:941–7.CrossRefPubMed
28.
Zurück zum Zitat Bernier J, Cooper JS, Pajak TF, 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;27:843–50.CrossRefPubMed Bernier J, Cooper JS, Pajak TF, 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;27:843–50.CrossRefPubMed
29.
Zurück zum Zitat Puri SK, Fan CY, Hanna E. Significance of extracapsular lymph node metastases in patients with head and neck squamous cell carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2003;11:119–23.CrossRefPubMed Puri SK, Fan CY, Hanna E. Significance of extracapsular lymph node metastases in patients with head and neck squamous cell carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2003;11:119–23.CrossRefPubMed
30.
Zurück zum Zitat Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. New Engl J Med. 2004;350:1945–52.CrossRefPubMed Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. New Engl J Med. 2004;350:1945–52.CrossRefPubMed
31.
Zurück zum Zitat Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. New Engl J Med. 2004;350:1937–44.CrossRefPubMed Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. New Engl J Med. 2004;350:1937–44.CrossRefPubMed
Metadaten
Titel
Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer
verfasst von
N. Gopalakrishna Iyer, MD, PhD
Snjezana Dogan, MD
Frank Palmer, BA
Rahmatullah Rahmati, MD
Iain J. Nixon, MD
Nancy Lee, MD
Snehal G. Patel, MD
Jatin P. Shah, MD
Ian Ganly, MD, PhD
Publikationsdatum
01.12.2015
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 13/2015
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4525-0

Weitere Artikel der Ausgabe 13/2015

Annals of Surgical Oncology 13/2015 Zur Ausgabe

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.