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?

Abstract

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.

Fig 1. Age-adjusted incidence trends by calendar year of diagnosis for head and neck squamous cell carcinoma (HNSCC) by sites and gender.

Panel a and b show a significant decrease in the incidence of HNSCC from human papillomavirus (HPV)-unrelated sites (the oral cavity and the larynx/hypopharynx) in males; for females a significant increase was observed for oral cavity HNSCC and a stable trend for larynx/hypopharynx HNSCC. The incidence of HNSCC from HPV-related sites has been significantly increasing in females, but it is stable in males; bars indicate the 95% confidence interval.

Fig 2. Age-adjusted incidence trends by calendar year of diagnosis for head and neck squamous cell carcinoma (HNSCC) by sites, gender, and age group.

Panels a and b outline the incidence trends in HPV-related HNSCC by age class showing the largest increase in females over 60 and a decrease in the males between 40 and 49. Panel c and d depict a significant increase in the incidence of oral cavity cancers in females over 50; a decline was observed in the males over 40. Panel e and f depict incidence trends for laryngeal and hypopharyngeal SCCs showing a significant decrease in females over 60 and a significant decrease in males in all age groups. APC annual percent change (star indicates significant difference at P < 0.05).

Fig 3. Five-year age standardized relative survival by calendar year and different head and neck sites.

The figure shows a significantly improved survival in patients with head and neck squamous cell carcinomas arising from human papillomavirus-related sites and from the oral cavity. Expected survival was calculated using the Ederer II method. Age standardized relative survival since diagnosis is the weighted average of age-specific relative survival according to the International Cancer Survival Standard. Bars indicate confidence interval at 95%. APC annual percent change (star indicates significant difference at P < 0.05).