Prevalence of Transcriptionally Active HPV Infection in Tumor-Free Oropharyngeal Tissue of OPSCC-Patients

Vittoria Guarda; Lea Schroeder; Michael Pawlita; Kristian Ikenberg; Niels J Rupp; Wolfram Jochum; Sandro J Stoeckli; Dana Holzinger; Martina A Broglie

doi:10.3389/fonc.2022.835814

Prevalence of Transcriptionally Active HPV Infection in Tumor-Free Oropharyngeal Tissue of OPSCC-Patients

Front Oncol. 2022 Apr 22:12:835814. doi: 10.3389/fonc.2022.835814. eCollection 2022.

Authors

Vittoria Guarda¹, Lea Schroeder², Michael Pawlita², Kristian Ikenberg³, Niels J Rupp³, Wolfram Jochum⁴, Sandro J Stoeckli⁵, Dana Holzinger², Martina A Broglie¹

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
² Infections and Cancer Epidemiology, Infection Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland.
⁴ Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Abstract

Objectives: The natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is still largely unknown. Since reports of second primary tumors (SPTs) in patients with HPV-related OPSCCs are increasing, a multifocal HPV infection, hinting a «virus-induced field effect», has been hypothesized. This study aimed to investigate the HPV-prevalence in normal appearing oropharyngeal tissue in patients with OPSCCs.

Materials and methods: 49 OPSCC patients undergoing panendoscopy were prospectively enrolled. Tumor specimens and biopsies of normal appearing oropharyngeal tissue adjacent to and distant from the index OPSCC underwent histopathological examination, p16^INK4A immunohistochemical staining, HPV DNA and mRNA-detection. Patient characteristics and follow-up data on SPTs were obtained.

Results: 26 of 49 (53%) OPSCC were positive for HPV DNA and p16^INK4A. HPV mRNA was detected in 23 of 26 (88%) of these tumor samples. HPV DNA was detected in 36% adjacent mucosa and in 17% distant mucosa samples and only in patients with an HPV-related index OPSCC. HPV mRNA could not be detected in tumor-free distant and adjacent mucosa samples. No evidence of association between HPV detection in normal appearing mucosa and development of second primary tumors was found.

Conclusions: HPV was detectable but not transcriptionally active in adjacent/distant tumor-free oropharyngeal tissue. This suggests that a multifocal HPV infection, hinting a «virus-induced fielcd cancerization», may not be pertaining to HPV-related OPSCC.

Keywords: head and neck cancer; human papillomavirus; human papillomavirus DNA tests; oropharynx cancer; second primary neoplasms.