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. 2014 Mar 1;88(3):580-8.
doi: 10.1016/j.ijrobp.2013.11.246.

Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis

Matthew H Stenmark  1 , Jonathan B McHugh  2 , Matthew Schipper  3 , Heather M Walline  4 , Christine Komarck  4 , Felix Y Feng  5 , Francis P Worden  6 , Gregory T Wolf  4 , Douglas B Chepeha  4 , Mark E Prince  4 , Carol R Bradford  4 , Suresh K Mukherji  7 , Avraham Eisbruch  5 , Thomas E Carey  4
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Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis

Matthew H Stenmark et al. Int J Radiat Oncol Biol Phys. .

Abstract

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 EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded 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 HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001).

Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

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Figures

Figure 1
Figure 1
Increasing incidence of human papillomavirus (HPV)-positive nasopharyngeal carcinoma over time.
Figure 2
Figure 2
Kaplan-Meier plots stratified by viral status (EBV-positive, HPV-positive, and EBV/HPV-negative). Overall survival (A), progression-free survival (B), locoregional control (C), and distant control (D).
See this image and copyright information in PMC

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