Background Nasopharyngeal carcinoma (NPC) is related to Epstein‐Barr virus (EBV) in endemic areas; however, the role of viruses in nonendemic countries is unclear. Our nationwide study investigated the prevalence and prognostic significance of EBV and human papillomaviruses (HPVs) in Finnish NPC tumors. Methods We analyzed samples from 150 patients diagnosed between 1990 and 2009. Viral status was determined using EBV and HPV RNA in situ hybridizations, and p16 immunohistochemistry. Patient and treatment characteristics were obtained from patient records. Results In our white patient cohort, 93 of 150 (62%) patients were EBV‐positive and 21/150 (14%) patients were HPV‐positive with no coinfections. Thirty‐six (24%) tumors were negative for both viruses. The 5‐year disease‐specific survival for patients with EBV‐positive, HPV‐positive, and EBV/HPV‐negative tumors was 69%, 63%, and 39%, respectively. In multivariable‐adjusted analysis, overall survival was better among patients with EBV‐positive ( P = .005) and HPV‐positive ( P = .03) tumors compared to patients with EBV/HPV‐negative tumors. Conclusions In our low‐incidence population, EBV and HPV are important prognostic factors for NPC.

The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been studied recently in many cancers. For the first time in a nonendemic region, we have evaluated the prognostic value of TILs in a whole population-based nationwide cohort of nasopharyngeal carcinoma (NPC) in Finland. A total of 115 cases from Finnish hospitals were included. TILs were analyzed using hematoxylin and eosin-stained slides according to the criteria of the International Immuno-Oncology Biomarker Working Group. TILs were evaluated separately in stromal and tumor compartments. The log-rank test and univariable and multivariable analyses were used to compare survival in patients with tumors with low and high TILs. A significant positive correlation was observed between the occurrence of intratumoral and stromal TILs (P < .001). In multivariable analysis, NPC cases with low intratumoral TILs had poor overall survival with a hazard ratio (HR) of 2.55 and 95% confidence interval (95% CI) of 1.60 to 4.05 (P < .001). Cases with low intratumoral TILs also had poor disease-specific survival (HR, 2.02; 95% CI, 1.16-3.52; P = .015). Keratinized tumors with low intratumoral TILs were associated with an even poorer overall survival (HR, 3.94; 95% CI, 2.17-7.15; P < .001) and a poor disease-specific survival (HR, 2.97; 95% CI, 1.46-6.05; P = .009). Our study demonstrates that the evaluation of TILs is simple and can be assessed routinely in NPC.

Background Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. Methods In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. Results We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2 nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2 nucl /TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). Conclusions TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.