Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000-2022 in Northeastern Italy: Implication for Using p16INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis

Paolo Boscolo-Rizzo; Jerry Polesel; Annarosa Del Mistro; Elisabetta Fratta; Chiara Lazzarin; Anna Menegaldo; Valentina Lupato; Giuseppe Fanetti; Fabrizio Zanconati; Maria Guido; Vittorio Giacomarra; Enzo Emanuelli; Margherita Tofanelli; Giancarlo Tirelli

doi:10.3390/cancers15092643

Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000-2022 in Northeastern Italy: Implication for Using p16^INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis

Cancers (Basel). 2023 May 7;15(9):2643. doi: 10.3390/cancers15092643.

Affiliations

¹ Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy.
² Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy.
³ Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy.
⁴ Unit of Immunopathology and Cancer Biomarkers, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy.
⁵ Unit of Otolaryngology, AULSS 2 Marca Trevigiana, Piazzale dell'Ospedale 1, 31100 Treviso, Italy.
⁶ Unit of Otolaryngology, General Hospital "S. Maria degli Angeli", Via Montereale 24, 33170 Pordenone, Italy.
⁷ Department of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy.
⁸ Department of Medical, Surgical and Health Sciences, Section of Pathology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy.
⁹ Department of Medicine, Section of Pathology, University of Padova, via Giustiniani 2, 35128 Padova, Italy.

Abstract

Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16^INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value.

Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16^INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16^INK4a overexpression.

Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000-2006 to 50% in 2019-2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16^INK4a positive predictive value was 89% for the former and 29% for the latter.

Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16^INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.

Keywords: biomarker; epidemiology; head and neck cancer; human papillomavirus; oropharyngeal cancer; p16INK4a; prevalence; squamous cell carcinoma.

Grants and funding

The work of J.P., E.F. and G.F. was partially supported by Italian Ministry of Health (Ricerca Corrente) and 5 × 1000 Intramural Grant from CRO.