Research Article: The evolution of the epidemiological landscape of head and neck cancer in Italy: Is there evidence for an increase in the incidence of potentially HPV-related carcinomas?

Date Published: February 7, 2018

Publisher: Public Library of Science

Author(s): Paolo Boscolo-Rizzo, Manuel Zorzi, Annarosa Del Mistro, Maria Cristina Da Mosto, Giancarlo Tirelli, Carlotta Buzzoni, Massimo Rugge, Jerry Polesel, Stefano Guzzinati, Maria Lina Tornesello.


The current study aimed to investigate the incidence and survival patterns of HNSCCs arising from different anatomic sites, potentially related (the oropharynx) or unrelated (the oral cavity, the larynx/hypopharynx) to HPV, to provide clues on possible growing impact of HPV in the epidemiology of HNSCC in Italy. Epidemiological data were retrieved from ten long-term Cancer Registries covering a population of 7.8 million inhabitants. Trends were described by means of the estimated annual percent change (APC) stratified by age and gender, and compared between HPV-related and HPV-unrelated anatomical sites. The data regarding 28,295 HNSCCs diagnosed in Italy between 1988 and 2012 were analyzed. In males, the incidence rate (IR) of cancers arising from sites unrelated to HPV infection significantly decreased in all age groups (APC:-3.31 for larynx/hypopharynx; APC:-1.77 for oral cavity), whereas stable IR were observed for cancers arising from sites related to HPV infection. In females, IR for cancers from HPV-related sites increased significantly over the observed period; the largest increment was noted in those over 60 (APC:2.92%) who also showed a significantly lower number of HNSCCs from the larynx/hypopharynx (APC:- 0.84) and a significantly higher number of oral cavity tumors (APC = 2.15). The five-year relative survival remained largely unchanged in the patients with laryngeal/hypopharyngeal SCC and, conversely, significantly improved in the patients with SCC at HPV-related sites. The trends observed suggest a potential increasing impact of HPV infection on the epidemiology of HNSCC in Italy, but to a lesser extent and with a different pattern from that observed in other Western countries.

Partial Text

In 2020, head and neck cancer (HNC) is expected to affect approximately 833,000 and 151,000 new patients worldwide and in Europe, respectively [1]. HNC is a frequently lethal cancer that mainly develops in the epithelial linings of the upper aero-digestive tract (the oral cavity, the oropharynx, the hypopharynx, and the larynx). Most HNCs are squamous cell carcinomas (HNSCCs) traditionally considered tobacco and alcohol exposure related [2]. High risk alpha human papillomaviruses (HPV)s, mainly HPV type 16 (HPV16), have recently been recognized as causally related to a subset of oropharyngeal squamous cell carcinomas (OPSCCs) arising from the crypt epithelium of the palatine and lingual tonsils as well as to a substantial fraction of SCCs from unknown primary metastatic to the neck nodes. Both of these entities benefit from a significantly better prognosis [3–5]. Thus, HNSCC can be classified in HPV-related when arising from sites in which a substantial, though geographically varying, proportion of cases is caused by HPV infection and in HPV-unrelated when arising from head and neck sites where the etiological contribution of HPV is extremely marginal. As a sexually transmitted disease, the odds of HPV-positive OPSCC are associated, in a dose-dependent fashion, with several collinear sexual behaviors [6].

This cancer registry-based study addressed trends in HNSCC incidence at different anatomic sites in Italy in relation to their potential association with HPV infection in Italy over a 25-year period. Overall, the analysis of APC basically identified three different patterns: 1. cancers whose incidence is increasing (SCC at HPV-related and oral cavity sites, both in females); 2. cancers whose incidence is decreasing (SCC of the oral cavity and the larynx/hypopharynx, both in males); 3. cancers whose incidence was substantially constant over the observation period (SCC at HPV-related sites in males and SCC of the larynx/hypopharynx in females). Thus, the analysis confirmed that the incidence rates varied depending on the site and gender.

Topographically restricted to the oropharynx, HPV-driven HNSCCs, which exhibit a survival benefit compared to HPV-unrelated tumors, have been increasing rapidly in several Western countries. Although to a lesser extent and following different patterns with respect to those observed in other Western countries, the trends in HNSCC incidence and survival rates at the different sites examined here suggest a potential increasing impact of HPV infection on oropharyngeal oncogenesis in Italy. One thousand five hundred sixty-five SCCs are expected to arise from HPV-related sites in Italy in 2017. According to the recent analyses, the fraction of OPSCCs driven by HPV infection in Southern Europe is estimated at between 20 and 30% [8]. Besides its connection to cervical cancer, HPV is also causally related to other anogenital cancers in both females and males. HPV cancer burden can be reduced if primary and secondary prevention strategies are prioritized in both genders. Particularly, every effort should be made to reinforce the adherence to HPV vaccination programs. Finally, future research should aim to identify new causative factors in SCC arising from the oral cavity.




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