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

Abstract

ObjectivesThe 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 Methods49 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, p16INK4A immunohistochemical staining, HPV DNA and mRNA-detection. Patient characteristics and follow-up data on SPTs were obtained.Results26 of 49 (53%) OPSCC were positive for HPV DNA and p16INK4A. 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.ConclusionsHPV 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.