Epstein-Barr Virus and Human Papillomavirus Infections and Genotype Distribution in Head and Neck Cancers

Abstract

ObjectiveTo investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).Methods and MaterialsHPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER) was examined by in situ hybridization.ResultsOf the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1–3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).ConclusionsOur findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.

Human Papillomavirus Laboratory Testing: the Changing Paradigm

“…Compiled studies have shown that most OPSCC are mediated by HPV16 (76 to 95%), followed by HPV18 (1 to 8%) with HPV33, -35, -56, -58, and -67 found infrequently (37,44,45). In 2009, the IARC recognized HPV16 as a causal agent in OPSCC (46).…”

The interaction between human papillomavirus and other viruses

“…Elevated IgA antibody titers to EBV capsid and early antigens is predictive of NPC development within a window of about 3 years (Henle et al, 1970; Ji et al, 2007). Despite the nearly complete association of EBV in type 2/3 endemic NPC, HPV has been detected at frequencies ranging from 10 – 47% in endemic NPC cohorts from Japan, Iran, Morocco, and China (Deng et al, 2014; Laantri et al, 2011; Mirzamani et al, 2006; Tung et al, 1999). Although both low-risk and high-risk HPVs (6, 11, 16, and 18) were detected, HPV16 and 18 were more prevalent, accounting for 66.7% of HPV-positive NPC tumors in a Chinese cohort (Tung et al, 1999).…”

Viruses and Head and Neck Cancers

“…A study recently performed on a cohort of Japanese HNC to investigate the frequency of EBV and HPV in fresh frozen samples to analyze the effect of co-infection on different types of HNC. The findings revealed that although HPV and EBV are highly prevalent in subset of oropharynx and nasopharynx of HNC simultaneous infection or co-infection is rare [1]. Another report published this year by Cooper et al reported that although oncolytic reovirus demonstrate significant destruction of HNC cells the oncolysis is significantly greater in HPV negative HNC cell lines as compared to HPV positive ones [9].…”

“…Many cancers including the head and neck group of cancers (HNC) are caused by oncogenic strains of viruses like Human papillomavirus (HPV) and Epstein -Barr virus (EBV) [1]. Interestingly certain viruses also possess the cancer eliminating properties and reovirus (RV) a double stranded RNA virus is a prominent one with significant research guided relevance [2].…”

“…The herpes viruses consist of generally large, complex DNA viruses, able to encode about 100 different proteins, and are one of the largest virus groups [1]. This virus affects more than 90% of the world's adult population in some form or other.…”