Clinical Value of the Epstein-Barr Virus and p16 Status in Patients with Nasopharyngeal Carcinoma: A Single-Centre Study in Japan

Abstract

Background: The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC). Methods: We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA. Results: Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically >60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (<60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival. Conclusion: In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous.

Association Between LMP-1 and p16 Expression with Prognostic Factor of Nasopharyngeal Carcinoma

“…12 Other studies report that p16 expression of nasopharynx cancer is higher than usual or chronic inflammation of nasopharyngeal tissue. 16 In the current study, univariate and multivariate analyses revealed that the association between p16 expression with nodal status/pN and staging/ S were significantly correlated (P< 0.05). A previous study found that p16 regulates nodal spread via integrin.…”

Human papillomavirus and World Health Organization type III nasopharyngeal carcinoma: Multicenter study from an endemic area in Southern China

“…23 Data from the nonendemic countries of Asia also demonstrated that HPV/p16 expression is uncommon in patients with NPC. 24,25 There are reports from other nonendemic regions of the world demonstrating a possible association between HPV and NPC and its potential influence on carcinogenesis. 26 In addition, there are postulations regarding the biological plausibility of the vertical, perinatal transmission of oncogenic HPV to newborns that puts them at risk of developing NPC subsequently, and hence the potential role of community control of HPV infection and newborn vaccination.…”

“…Jiang et al investigated 86 patients with NPC who were treated at The University of Texas MD Anderson Cancer Center in Houston between 2000 and 2014 and reported that p16 overexpression was found to be associated with improved progression‐free survival and locoregional control in patients with EBV+ NPC; they concluded that p16 expression may complement EBV status in predicting treatment outcomes for patients with NPC . Data from the nonendemic countries of Asia also demonstrated that HPV/p16 expression is uncommon in patients with NPC . There are reports from other nonendemic regions of the world demonstrating a possible association between HPV and NPC and its potential influence on carcinogenesis .…”

Clinicopathological and prognostic significance of p16 protein in nasopharynx cancer patients

“…Finally, 5 papers were further removed because of repeated data, and 35 articles with 2612 nasopharyngeal cancer patients were included. [16–50] 6 articles were English language and 29 literatures were Chinese language in the eligible studies. (Table 1, Table 2; Fig.…”