Cancer treatment and research communications · 2026
Human host factors Secretory leukocyte protease inhibitor and Annexin A2 modulate the presence of human papillomavirus DNA, but not Epstein-Barr virus, in nasopharyngeal carcinoma from non-endemic regions.
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Quabius Elgar S, Stuhlmann-Laeisz Christiane M, Zech Henrike B A A, Schultz Johannes, Remmert Stephan, Strüder Daniel F, Idel Christian, Park Jonas J-H, Seuthe Inga M C, Blaurock Markus, Geddert Helene, Wiegand Susanne, Hoffmann Markus
Аннотация
BACKGROUND: The human host factors Secretory leukocyte protease inhibitor (SLPI) and Annexin A2 (AnxA2) influence susceptibility of epithelial cells to human papillomavirus (HPV)-infections. Although nasopharyngeal carcinoma (NPC) is classically associated with Epstein-Barr virus (EBV), increasing evidence indicates that a subset of NPCs from non-endemic regions harbours HPV DNA, suggesting biological overlap with HPV-associated head and neck cancers. Therefore, we studied whether this host-driven mechanism also shapes NPC-biology.
METHODS: Retrospectively 44 histopathological confirmed NPC cases from non-endemic German regions were analysed. Nucleic acids were extracted from FFPE tissue. DNA was used for PCR-based detection of HPV and EBV, RNA was used for RT-PCR detection of HPV transcriptional activity and RT-qPCR for quantification of SLPI- and AnxA2-expression. Associations between viral-status, host factor expression, and clinicopathological parameters were assessed using Fisher's exact test, Student's t-test, and one way-ANOVA.
RESULTS: EBV was detected in 65.9% cases, HPV-DNA in 29.6%, all harboured HPV16-DNA; none expressed HPV16-RNA. EBV-status had no effect on SLPI-expression and was associated with lower AnxA2-levels. HPV-presence was associated with significantly lower SLPI- and higher AnxA2-expression, indicating a permissive epithelial environment for viral entry. Combined-status analyses confirmed that host factor expression paralleled the HPV-DNA- but not EBV-status.
CONCLUSIONS: These findings indicate that in NPC from non-endemic regions, SLPI- and AnxA2-expression defines a host microenvironment permissive for HPV-DNA, whereas EBV-status appears independent of these factors. As no HPV-RNA was detected, these results reflect HPV-presence rather than transcriptionally active infection, suggesting that these host factors may govern viral entry without determining subsequent infection.
METHODS: Retrospectively 44 histopathological confirmed NPC cases from non-endemic German regions were analysed. Nucleic acids were extracted from FFPE tissue. DNA was used for PCR-based detection of HPV and EBV, RNA was used for RT-PCR detection of HPV transcriptional activity and RT-qPCR for quantification of SLPI- and AnxA2-expression. Associations between viral-status, host factor expression, and clinicopathological parameters were assessed using Fisher's exact test, Student's t-test, and one way-ANOVA.
RESULTS: EBV was detected in 65.9% cases, HPV-DNA in 29.6%, all harboured HPV16-DNA; none expressed HPV16-RNA. EBV-status had no effect on SLPI-expression and was associated with lower AnxA2-levels. HPV-presence was associated with significantly lower SLPI- and higher AnxA2-expression, indicating a permissive epithelial environment for viral entry. Combined-status analyses confirmed that host factor expression paralleled the HPV-DNA- but not EBV-status.
CONCLUSIONS: These findings indicate that in NPC from non-endemic regions, SLPI- and AnxA2-expression defines a host microenvironment permissive for HPV-DNA, whereas EBV-status appears independent of these factors. As no HPV-RNA was detected, these results reflect HPV-presence rather than transcriptionally active infection, suggesting that these host factors may govern viral entry without determining subsequent infection.