Incidence trends and survival of human papillomavirus-related oropharyngeal cancer in the province of Girona (1994-2018): a population-based study of oropharyngeal cancer in Southern Europe

Abstract

Background: A shift in etiology in oropharyngeal cancer (OPC) has caused a change in the epidemiological trends of head and neck cancer (HNC): whilst overall HNC incidence has decreased, OPC incidence has sharply increased, giving rise to an epidemic of a new subtype of OPC related to human papillomavirus (HPV), which has been attributed better prognosis and distinct clinicopathological characteristics. The emergence of this entity has predominantly been studied in regions of high burden of oral HPV infection, such as North America and Northern/Western Europe, but little is known about the onset of HPV-related OPC in Southern Europe. Main objective: To determine the trends in the incidence of OPC, overall and in relation with p16 expression, between 1994 and 2018 in the population of the province of Girona. Design: A population-based retrospective observational cohort study conducted between October 2020 and November 2021. Methods: 509 cases of patients diagnosed with primary OPC from 1994 to 2018 were identified from the Cancer Registry of Girona (CRG) database. Incidence trends for overall OPC were calculated subsequently. All identified OPC cases from calendar periods 1998-1999, 2003-2005, 2009-2011, and 2016-2018, 227 cases in total, were selected for a p16 expression-based analysis to assess trends in incidence and survival of HPV-related OPC. Tumor samples of these cases were identified and determination of immunohistochemical expression of p16INK4a protein, which served as a surrogate biomarker for HPV involvement, was performed. Results: A significant increase in incidence (Annual Percentage Change (APC): 4.1) was observed between 2001 and 2018 in overall OPC. In the p16 expression-based analysis, a sharp, significant increase in incidence was observed as well in HPV-related OPC (APC: 12.8) from 1998 to 2018, whilst the incidence in HPV-unrelated OPC in this same period experienced no significant changes. Significant differences were found between HPV-related and HPV-unrelated OPC regarding 5-year observed survival, which was determined to be higher in HPV-related OPC (64.8% versus 43.4%), and distribution among sexes, but none regarding age at diagnosis. Conclusions: There has been a significant increase in the incidence of overall OPC from 2001 to 2018 and in that of HPV-related OPC from 1998 to 2018 in the province of Girona