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.
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: Carole Fakhry; Qiang Zhang; Phuc Felix Nguyen-Tân; David I Rosenthal; Randal S Weber; Louise Lambert; Andy M Trotti; William L Barrett; Wade L Thorstad; Christopher U Jones; Sue S Yom; Stuart J Wong; John A Ridge; Shyam S D Rao; James A Bonner; Eric Vigneault; David Raben; Mahesh R Kudrimoti; Jonathan Harris; Quynh-Thu Le; Maura L Gillison Journal: J Clin Oncol Date: 2017-08-04 Impact factor: 44.544
Authors: K Kian Ang; Jonathan Harris; Richard Wheeler; Randal Weber; David I Rosenthal; Phuc Felix Nguyen-Tân; William H Westra; Christine H Chung; Richard C Jordan; Charles Lu; Harold Kim; Rita Axelrod; C Craig Silverman; Kevin P Redmond; Maura L Gillison Journal: N Engl J Med Date: 2010-06-07 Impact factor: 91.245
Authors: K Kian Ang; Qiang Zhang; David I Rosenthal; Phuc Felix Nguyen-Tan; Eric J Sherman; Randal S Weber; James M Galvin; James A Bonner; Jonathan Harris; Adel K El-Naggar; Maura L Gillison; Richard C Jordan; Andre A Konski; Wade L Thorstad; Andy Trotti; Jonathan J Beitler; Adam S Garden; William J Spanos; Sue S Yom; Rita S Axelrod Journal: J Clin Oncol Date: 2014-09-20 Impact factor: 44.544
Authors: Justin A Bishop; Zahra Maleki; Alexandra Valsamakis; Takenori Ogawa; Xiaofei Chang; Sara I Pai; William H Westra Journal: Cancer Cytopathol Date: 2011-07-12 Impact factor: 5.284
Authors: Kara S Davis; J Kenneth Byrd; Vikas Mehta; Simon I Chiosea; Seungwon Kim; Robert L Ferris; Jonas T Johnson; Umamaheswar Duvvuri Journal: Otolaryngol Head Neck Surg Date: 2014-05-08 Impact factor: 3.497