Smoking-Induced SLPI Expression Hinders HPV Infections Also in Squamous Cell Carcinomas of the Vulva

Elgar S Quabius; Julius Loehr; Dirk Haaser; Veronika Günther; Nico Maass; Christoph Röcken; Micaela Mathiak; Ibrahim Alkatout; Markus Hoffmann

doi:10.1016/j.tranon.2018.09.004

Smoking-Induced SLPI Expression Hinders HPV Infections Also in Squamous Cell Carcinomas of the Vulva

Transl Oncol. 2019 Jan;12(1):36-42. doi: 10.1016/j.tranon.2018.09.004. Epub 2018 Sep 26.

Authors

Elgar S Quabius¹, Julius Loehr², Dirk Haaser², Veronika Günther³, Nico Maass³, Christoph Röcken⁴, Micaela Mathiak⁴, Ibrahim Alkatout³, Markus Hoffmann⁵

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany; Institute of Immunology Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
² Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
³ Department of Gynecology and Obstetrics, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany.
⁴ Institute for Pathology, Christian-Albrechts-University of Kiel, Germany.
⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, D-24105 Kiel, Germany. Electronic address: markus.hoffmann@uksh.de.

Abstract

In HNSCC, protein- and mRNA-expression of the antileukoproteinase SLPI are significantly inverse correlated with HPV-infection suggesting that elevated expression of SLPI protects against HPV-infections. Moreover, SLPI-expression is up-regulated in HNSCC-patients reporting a smoking habit. Here, we investigate the described correlation in other HPV-driven cancers, namely vulvar squamous cell carcinoma (VSCC). FFPE samples of 99 VSCC were analyzed by PCR for HPV-DNA-expression and by RT-qPCR for SLPI-mRNA-expression. Of 99 VSCC 10 (10.1%) are HPV-positive; 9 were HPV16; 1 HPV18; all were E6/E7 mRNA-positive. 33 of the 99 patients (33.3%) reported a smoking habit; 7 (21.1%) of these were HPV-positive. Of 66 (66.7%) non-smokers 3 (4.5%) were HPV-positive. SLPI-expression was 4.0-fold lower in HPV-positive than HPV-negative patients. Smoking resulted in 2.3-fold higher SLPI expression. The data presented here indicate that SLPI plays a pivotal role in HPV-infection not only in HNSCC but also in VSCC and possibly also in other HPV-driven cancers. This however, needs to be analyzed in future studies. Furthermore these data lead to the hypothesis that the smoking induced SLPI-increase is systemic rather than local, as assumed based on the HNSCC data.