Volume 127, Issue 10 pp. 2270-2278

Head and Neck

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States

Matthew H. Stenmark MD,

Matthew H. Stenmark MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Dean Shumway MD,

Corresponding Author

Dean Shumway MD

[email protected]

orcid.org/0000-0001-7758-8891

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Send correspondence to Dean Shumway, MD, Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109. E-mail: [email protected]Search for more papers by this author

Cui Guo MS,

Cui Guo MS

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Jeffrey Vainshtein MD,

Jeffrey Vainshtein MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Michelle Mierzwa MD,

Michelle Mierzwa MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Reshma Jagsi MD, DPhil,

Reshma Jagsi MD, DPhil

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Jennifer J. Griggs MD, MPH,

Jennifer J. Griggs MD, MPH

Department of Internal Medicine, Hematology and Oncology Division, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Mousumi Banerjee PhD,

Mousumi Banerjee PhD

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Matthew H. Stenmark MD,

Matthew H. Stenmark MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Dean Shumway MD,

Corresponding Author

Dean Shumway MD

[email protected]

orcid.org/0000-0001-7758-8891

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Cui Guo MS,

Cui Guo MS

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Jeffrey Vainshtein MD,

Jeffrey Vainshtein MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Michelle Mierzwa MD,

Michelle Mierzwa MD

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Reshma Jagsi MD, DPhil,

Reshma Jagsi MD, DPhil

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Jennifer J. Griggs MD, MPH,

Jennifer J. Griggs MD, MPH

Department of Internal Medicine, Hematology and Oncology Division, University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

Mousumi Banerjee PhD,

Mousumi Banerjee PhD

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, U.S.A.

Search for more papers by this author

First published: 17 March 2017

https://doi.org/10.1002/lary.26566

Citations: 36

Dr. Banerjee's research was partially funded by grant CA 046592 from the National Cancer Institute. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Share a link

Email
Wechat
Bluesky

Abstract

Objective

Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing.

Study Design

Retrospective, cross-sectional study.

Methods

We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status.

Results

Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P < 0.001). Advanced primary tumor stage was associated with HPV-negative disease (P < 0.001), whereas increasing nodal burden was associated with HPV-positive disease (P < 0.001). Despite less-advanced nodal disease, HPV-negative tumors were associated with a higher likelihood of metastasis at presentation (P < 0.001).

Conclusion

HPV now accounts for the majority of newly diagnosed oropharyngeal carcinoma in the United States and is associated with a distinct clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer.

Level of Evidence

4. Laryngoscope, 127:2270–2278, 2017

BIBLIOGRAPHY

1 Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29: 4294–4301.
10.1200/JCO.2011.36.4596
PubMed Web of Science® Google Scholar
2 Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol 2013; 31: 4550–4559.
10.1200/JCO.2013.50.3870
PubMed Web of Science® Google Scholar
3 Auluck A, Hislop G, Bajdik C, et al. Trends in oropharyngeal and oral cavity cancer incidence of Human Papillomavirus (HPV)-related and HPV-unrelated sites in a multicultural population: The British Columbia experience. Cancer 2010; 116: 2635–2644.
10.1002/cncr.25087
CAS PubMed Web of Science® Google Scholar
4 Hammarstedt L, Lindquist D, Dahlstrand H, et al. Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer 2006; 119: 2620–2623.
10.1002/ijc.22177
CAS PubMed Web of Science® Google Scholar
5 Braakhuis BJM, Visser O, Leemans CR. Oral and oropharyngeal cancer in The Netherlands between 1989 and 2006: Increasing incidence, but not in young adults. Oral Oncol 2009; 45: e85–e89.
10.1016/j.oraloncology.2009.03.010
PubMed Web of Science® Google Scholar
6 Conway DI, Stockton DL, Warnakulasuriya KAAS, et al. Incidence of oral and oropharyngeal cancer in United Kingdom (1990–1999)-recent trends and regional variation. Oral Oncol 2006; 42: 586–592.
10.1016/j.oraloncology.2005.10.018
CAS PubMed Web of Science® Google Scholar
7 Gillison ML. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000; 92: 709–720.
10.1093/jnci/92.9.709
CAS PubMed Google Scholar
8 Mehanna H, Beech T, Nicholson T, 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: 747–755.
10.1002/hed.22015
PubMed Web of Science® Google Scholar
9 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.
10.1200/JCO.2010.29.2904
CAS PubMed Web of Science® Google Scholar
10 Kian Ang K, Ang KK, Harris J, et al. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Engl J Med 2010; 363: 24–35.
10.1056/NEJMoa0912217
CAS PubMed Web of Science® Google Scholar
11 Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: A subset analysis from an international phase III trial. Ann Oncol 2011; 22: 1071–1077.
10.1093/annonc/mdr006
CAS PubMed Web of Science® Google Scholar
12 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: 261–269.
10.1093/jnci/djn011
CAS PubMed Web of Science® Google Scholar
13 Gillison ML, D'Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 2008; 100: 407–420.
10.1093/jnci/djn025
PubMed Web of Science® Google Scholar
14 Settle K, Posner MR, Schumaker LM, et al. Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev Res 2009; 2: 776–781.
10.1158/1940-6207.CAPR-09-0149
PubMed Web of Science® Google Scholar
15 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: 362–366.
10.1002/ijc.24339
CAS PubMed Web of Science® Google Scholar
16 Lassen P, Eriksen JG, Krogdahl A, et al. The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: evaluation of the randomised DAHANCA 6&7 trial. Radiother Oncol 2011; 100: 49–55.
10.1016/j.radonc.2011.02.010
CAS PubMed Web of Science® Google Scholar
17 Ryerson AB, Peters ES, Coughlin SS, et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998–2003. Cancer 2008; 113: 2901–2909.
10.1002/cncr.23745
PubMed Web of Science® Google Scholar
18 Chaturvedi AK, Engels EA, Anderson WF, et al. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008; 26: 612–619.
10.1200/JCO.2007.14.1713
PubMed Web of Science® Google Scholar
19 Bilimoria KY, Stewart AK, Winchester DP, et al. The National Cancer data base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 2008; 15: 683–690.
10.1245/s10434-007-9747-3
PubMed Web of Science® Google Scholar
20 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: 543–550.
10.1200/JCO.2012.44.0164
CAS PubMed Web of Science® Google Scholar
21 Lin BM, Wang H, D'Souza G, et al. Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer 2013; 119: 3462–3471.
10.1002/cncr.28250
PubMed Web of Science® Google Scholar
22 Vainshtein JM, Spector ME, McHugh JB, et al. Refining risk stratification for locoregional failure after chemoradiotherapy in human papillomavirus-associated oropharyngeal cancer. Oral Oncol 2014; 50: 513–519.
10.1016/j.oraloncology.2014.02.001
PubMed Web of Science® Google Scholar
23 Worsham MJ, Stephen JK, Chen KM, et al. Improved survival with HPV among African Americans with oropharyngeal cancer. Clin Cancer Res 2013; 19: 2486–2492.
10.1158/1078-0432.CCR-12-3003
PubMed Web of Science® Google Scholar
24 Zevallos JP, Sandulache VC, Hamblin J, et al. Impact of race on oropharyngeal squamous cell carcinoma presentation and outcomes among veterans. Head Neck 2016; 38: 44–50.
10.1002/hed.23836
PubMed Web of Science® Google Scholar
25 D'Souza G, Agrawal Y, Halpern J, et al. Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis 2009; 199: 1263–1269.
10.1086/597755
PubMed Web of Science® Google Scholar
26 Roetzheim RG, Pal N, Tennant C, et al. Effects of health insurance and race on early detection of cancer. J Natl Cancer Inst 1999; 91: 1409–1415.
10.1093/jnci/91.16.1409
CAS PubMed Web of Science® Google Scholar
27 Chen AY, Schrag NM, Halpern MT, et al. The impact of health insurance status on stage at diagnosis of oropharyngeal cancer. Cancer 2007; 110: 395–402.
10.1002/cncr.22788
PubMed Web of Science® Google Scholar
28 Huang SH, Perez-Ordonez B, Weinreb I, et al. Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol 2013; 49: 79–85.
10.1016/j.oraloncology.2012.07.015
PubMed Web of Science® Google Scholar
29 Nguyen-Tan PF, Zhang Q, Ang KK, et al. 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: 3858–3867.
10.1200/JCO.2014.55.3925
CAS PubMed Web of Science® Google Scholar
30 Jordan RC, Lingen MW, Perez-Ordonez B, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 2012; 36: 945–954.
10.1097/PAS.0b013e318253a2d1
PubMed Web of Science® Google Scholar
31 Sturgis EM, Dahlstrom KR, Garden AS, et al. Proposed staging system for patients with HPV-related oropharyngeal cancer based on nasopharyngeal cancer N categories. J Clin Oncol 2016; 34: 1848–1854.
10.1200/JCO.2015.64.6448
PubMed Web of Science® Google Scholar
32 Huang SH, Xu W, Waldron J, et al. Refining American joint committee on cancer/union for international cancer control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol 2015; 33: 836–845.
10.1200/JCO.2014.58.6412
PubMed Web of Science® Google Scholar
33 Quon H, Forastiere AA. Controversies in treatment deintensification of human papillomavirus-associated oropharyngeal carcinomas: should we, how should we, and for whom? J Clin Oncol 2013; 31: 520–522.
10.1200/JCO.2012.46.7746
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume127, Issue10

October 2017

Pages 2270-2278

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States

Abstract

Objective

Study Design

Methods

Results

Conclusion

Level of Evidence

BIBLIOGRAPHY

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States

Abstract

Objective

Study Design

Methods

Results

Conclusion

Level of Evidence

BIBLIOGRAPHY

Citing Literature

References

Related

Information