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
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