Epstein‐Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: A nationwide study in Finland

Abstract

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.

Epstein‐Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country

“…The role of smoking as a risk factor has been examined in several studies in both, low incidence and endemic regions, and the risk associated with smoking has been shown to be higher in low incidence countries 11 . More recently, several studies also described human papillomavirus (HPV) as a risk factor for NPCs in low incidence regions, although the causal link remains under debate 12‐15 …”

“…In OPCs, early antigen HPV serology (especially antibodies against the HPV16 oncoprotein E6) has been shown to be very strongly associated with molecularly defined HPV‐positive OPCs, both at diagnosis and prospectively 17,20,21 . HPV detection in NPCs has been limited to p16 immunohistochemistry (IHC) and HPV DNA detection by PCR or in situ hybridization (ISH) 12‐15 . Currently, no serological assay has been validated for detecting HPV‐positive NPCs.…”

Epstein–Barr virus (EBV) and polyomaviruses are detectable in oropharyngeal cancer and EBV may have prognostic impact

“…Several viruses have been detected in head and neck squamous cell carcinoma (HNSCC) [1][2][3][4][5][6][7]. Their etiologic and prognostic role is of great interest in cancer prevention and new management practices including immunotherapy [8][9][10] and treatment de-escalation [11][12][13].…”

Mapping of human papilloma virus, p16, and epstein‐barr virus in non‐malignant tonsillar disease

“…31 In a study from 2019, Ruuskanen et al demonstrated presence of EBV in 62%, and HPV in 14% of cases of nasopharyngeal carcinoma, without coinfection. 60 Drop et al reported HPV/EBV co-infection in cancer of the oropharynx, larynx, and oral cavity in 28.6%, 21.4%, and 50%, respectively. 61 However, most patients in this study also had classical risk factors (smoking and alcohol abuse) for developing oropharyngeal cancer, which also could influence susceptibility to infection.…”

“…Co‐infection was not found in epithelial tumors of the head and neck by Atula et al, but could be seen in a study by Jiang et al in tonsillar cancer and cancer of the base of tongue in 25% and 70% of cases, respectively . In a study from 2019, Ruuskanen et al demonstrated presence of EBV in 62%, and HPV in 14% of cases of nasopharyngeal carcinoma, without co‐infection . Drop et al reported HPV/EBV co‐infection in cancer of the oropharynx, larynx, and oral cavity in 28.6%, 21.4%, and 50%, respectively .…”