COMBINED EPSTEIN-BARR-VIRUS AND HUMAN-PAPILLOMAVIRUS INFECTION IN NASOPHARYNGEAL CARCINOMA

Epstein Barr virus (EBV) has been shown to be a Likely etiologic agent in nasopharyngeal carcinogenesis. Human papillomaviruses (HPVs) have previously been identified in numerous upper aerodigestive tract carci nomas. This pilot study was undertaken to investigate the prevalence o f combined EBV and HPV infection in 17 patients with nasopharyngeal ca rcinoma (NPCA) using polymerase chain reaction (PCR). The primary goal was to determine if the presence of HPV could be correlated with mole cular, histologic, or clinical parameters. There were seven patients w ith undifferentiated NPCA (World Health Organization [WHO] type III) a nd 10 patients with squamous cell carcinoma (WHO type I). All 17 patie nts had stage IV disease at presentation. EBV was identified in 15 pat ients (88.2%), and HPV subtypes were identified in samples from nine p atients (52.9%). All HPV-positive cases were also EBV positive. Wester n blot analysis of six samples showed a high level of expression of c- myc and cdc2 kinase and a low level of p53 protein in NPCAs that conta ined both HPV and EBV (n = 3). Increased expression of c-myc and cdc2 kinase was seen in the cases that contained EBV only, but to a lesser extent (n = 2). These findings indicate an effect of the virus on cell ular proliferation and differentiation. Similarly, an elevated level o f Rb protein was found only in the HPV-containing NPCAs. Moderate diff erentiation (keratinization) occurred in four of eight HPV-negative an d none of the nine HPV-positive NPCAs. (All HPV-positive cases were po orly differentiated or undifferentiated.) This difference is statistic ally significant For this sample size (P < 0.03). There was a trend fo r the group that was HPV positive to have WHO III histology and for th e HPV negative group to have WHO I. The presence of HPV could not be c orrelated with any clinical parameters in this small group of patients with advanced disease; however, these data suggest that coexistence o f EBV and HPV infection may be a factor in the pathogenesis of NPCA an d may have an effect on regulation of cellular proliferation and diffe rentiation.