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Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin.
Clin Cancer Res. 2003 Dec 15; 9(17):6469-75.CC

Abstract

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.

Authors+Show Affiliations

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14695150

Citation

Begum, Shahnaz, et al. "Detection of Human Papillomavirus in Cervical Lymph Nodes: a Highly Effective Strategy for Localizing Site of Tumor Origin." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 9, no. 17, 2003, pp. 6469-75.
Begum S, Gillison ML, Ansari-Lari MA, et al. Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res. 2003;9(17):6469-75.
Begum, S., Gillison, M. L., Ansari-Lari, M. A., Shah, K., & Westra, W. H. (2003). Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 9(17), 6469-75.
Begum S, et al. Detection of Human Papillomavirus in Cervical Lymph Nodes: a Highly Effective Strategy for Localizing Site of Tumor Origin. Clin Cancer Res. 2003 Dec 15;9(17):6469-75. PubMed PMID: 14695150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. AU - Begum,Shahnaz, AU - Gillison,Maura L, AU - Ansari-Lari,M Ali, AU - Shah,Keerti, AU - Westra,William H, PY - 2003/12/26/pubmed PY - 2004/8/6/medline PY - 2003/12/26/entrez SP - 6469 EP - 75 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 9 IS - 17 N2 - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/14695150/Detection_of_human_papillomavirus_in_cervical_lymph_nodes:_a_highly_effective_strategy_for_localizing_site_of_tumor_origin_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=14695150 DB - PRIME DP - Unbound Medicine ER -