| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
1 Departments of Pathology,
2 Oncology,
3 Molecular Microbiology and Immunology, and
4 Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Purpose: Patients with head and neck squamous cell carcinoma (HNSCC) often come to clinical attention with a neck mass due to metastatic spread to lymph nodes. Treatment is dictated by the subsequent determination of primary tumor site and stage. However, the primary site remains elusive in some patients even after an exhaustive examination. Human papillomavirus type 16 (HPV-16) is an important etiologic agent for HNSCCs that arise within the oropharynx but less so for tumors from nonoropharyngeal sites. Detection of HPV-16 or a surrogate marker may be useful in localizing tumor origin in patients who present with metastatic HNSCC.
Experimental Design: We performed in situ hybridization (ISH) for HPV-16 on lymph node metastases from 68 patients with HNSCC. P16 immunohistochemistry was also performed because HPV-16 integration disrupts the retinoblastoma pathway and induces an overexpression of p16.
Results: HPV-16 was detected in 22 of the 68 (32%) cases by ISH. When stratified by site of origin, HPV-16 was detected in 22 of 31 (71%) metastases from the oropharynx, but in none of the 37 (0%) metastases from other sites (P < 0.001; Fisher’s exact). P16 expression was associated with the presence of HPV-16 by ISH: 21 of 22 HPV-16 positive tumors exhibited p16 expression, whereas only 4 of the 46 HPV-16-negative tumors were p16 positive (95% versus 9%; P < 0.001; Fisher’s exact). P16 expression in the node metastases also correlated with site of tumor origin: 24 of 31 oropharyngeal tumors were p16 positive, whereas only 1 of 37 nonoropharyngeal tumors was p16 positive (77% versus 3%; P < 0.001; Fisher’s exact).
Conclusions: For patients with metastatic HNSCC, detection of HPV-16 is a reliable way to establish origin from the oropharynx, either directly by ISH or indirectly by immunohistochemistry for p16 overexpression.
This article has been cited by other articles:
|
|
 |
|
  B. Kumar, K. G. Cordell, J. S. Lee, F. P. Worden, M. E. Prince, H. H. Tran, G. T. Wolf, S. G. Urba, D. B. Chepeha, T. N. Teknos, 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., July 1, 2008; 26(19): 3128 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fakhry, W. H. Westra, S. Li, A. Cmelak, J. A. Ridge, H. Pinto, A. Forastiere, and M. L. Gillison Improved Survival of Patients With Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial J Natl Cancer Inst, February 20, 2008; 100(4): 261 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Begum, M. L. Gillison, T. L. Nicol, and W. H. Westra Detection of Human Papillomavirus-16 in Fine-Needle Aspirates to Determine Tumor Origin in Patients with Metastatic Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., February 15, 2007; 13(4): 1186 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Gillison Human Papillomavirus and Prognosis of Oropharyngeal Squamous Cell Carcinoma: Implications for Clinical Research in Head and Neck Cancers J. Clin. Oncol., December 20, 2006; 24(36): 5623 - 5625. [Full Text] [PDF]
|
|
|
|
|
|
L. Licitra, F. Perrone, P. Bossi, S. Suardi, L. Mariani, R. Artusi, M. Oggionni, C. Rossini, G. Cantu, M. Squadrelli, et al. High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma J. Clin. Oncol., December 20, 2006; 24(36): 5630 - 5636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fakhry and M. L. Gillison Clinical Implications of Human Papillomavirus in Head and Neck Cancers J. Clin. Oncol., June 10, 2006; 24(17): 2606 - 2611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Perez-Ordonez, M Beauchemin, and R C K Jordan Molecular biology of squamous cell carcinoma of the head and neck. J. Clin. Pathol., May 1, 2006; 59(5): 445 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Weinberger, Z. Yu, B. G. Haffty, D. Kowalski, M. Harigopal, J. Brandsma, C. Sasaki, J. Joe, R. L. Camp, D. L. Rimm, et al. Molecular Classification Identifies a Subset of Human Papillomavirus-Associated Oropharyngeal Cancers With Favorable Prognosis J. Clin. Oncol., February 10, 2006; 24(5): 736 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Begum, D. Cao, M. Gillison, M. Zahurak, and W. H. Westra Tissue Distribution of Human Papillomavirus 16 DNA Integration in Patients with Tonsillar Carcinoma Clin. Cancer Res., August 15, 2005; 11(16): 5694 - 5699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yu, P. M. Weinberger, B. G. Haffty, C. Sasaki, C. Zerillo, J. Joe, D. Kowalski, J. Dziura, R. L. Camp, D. L. Rimm, et al. Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma Clin. Cancer Res., February 1, 2005; 11(3): 1160 - 1166. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
