International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation: Head and Neck Cancer
Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis Matthew H. Stenmark, MD,* Jonathan B. McHugh, MD,y Matthew Schipper, PhD,*,z Heather M. Walline, MA,x Christine Komarck, BS,x Felix Y. Feng, MD,* Francis P. Worden, MD,jj Gregory T. Wolf, MD,x Douglas B. Chepeha, MD,x Mark E. Prince, MD,x Carol R. Bradford, MD,x Suresh K. Mukherji, MD,{ Avraham Eisbruch, MD,* and Thomas E. Carey, PhDx Departments of *Radiation Oncology, yPathology, zBiostatistics, xHead and Neck Surgery, jjMedical Oncology, and { Radiology, University of Michigan Medical Center, Ann Arbor, Michigan Received Oct 3, 2013, and in revised form Nov 13, 2013. Accepted for publication Nov 25, 2013.
Summary This study identifies a unique subset of Epstein-Barr virus (EBV)-negative nasopharyngeal carcinoma among white patients that is strongly associated with oncogenic human papillomavirus (HPV). Patients with HPV-positive nasopharyngeal carcinoma exhibit distinct clinical behavior from those with EBV-positive nasopharyngeal carcinoma, with increased risks of locoregional relapse and death. The differences in clinical outcomes, however, cannot be attributed to viral status alone, given a correlation between tobacco exposure and HPV-positive tumors.
Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBVand high-risk HPV. EBV status was determined by the use of in situ hybridization for EBVencoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPVpositive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBVand HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation: Head and Neck Cancer
Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis Matthew H. Stenmark, MD,* Jonathan B. McHugh, MD,y Matthew Schipper, PhD,*,z Heather M. Walline, MA,x Christine Komarck, BS,x Felix Y. Feng, MD,* Francis P. Worden, MD,jj Gregory T. Wolf, MD,x Douglas B. Chepeha, MD,x Mark E. Prince, MD,x Carol R. Bradford, MD,x Suresh K. Mukherji, MD,{ Avraham Eisbruch, MD,* and Thomas E. Carey, PhDx Departments of *Radiation Oncology, yPathology, zBiostatistics, xHead and Neck Surgery, jjMedical Oncology, and { Radiology, University of Michigan Medical Center, Ann Arbor, Michigan Received Oct 3, 2013, and in revised form Nov 13, 2013. Accepted for publication Nov 25, 2013.
Summary This study identifies a unique subset of Epstein-Barr virus (EBV)-negative nasopharyngeal carcinoma among white patients that is strongly associated with oncogenic human papillomavirus (HPV). Patients with HPV-positive nasopharyngeal carcinoma exhibit distinct clinical behavior from those with EBV-positive nasopharyngeal carcinoma, with increased risks of locoregional relapse and death. The differences in clinical outcomes, however, cannot be attributed to viral status alone, given a correlation between tobacco exposure and HPV-positive tumors.
Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBVand high-risk HPV. EBV status was determined by the use of in situ hybridization for EBVencoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPVpositive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBVand HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P
