ECHO: the epidemiology of HPV infection in oropharyngeal, oral cavity, and laryngeal cancer in Ireland

Abstract

Human Papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). There is mounting evidence from North America and Europe to suggest that HPV-related HNSCC is becoming the principal driver of increasing incidence trends amongst all HNSCC. HPV-unrelated cases have seen a plateau or a decline in incidence in the last 20 to 30 years. No data on the epidemiology of HPV infection in oropharyngeal, oral cavity, and laryngeal SCC in Ireland currently exists in the literature, and thus the ECHO study was carried out to investigate the epidemiology of HPV infection in oropharyngeal, oral cavity, and laryngeal SCC in Ireland between 1994 and 2013. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC cases, identified through the National Cancer Registry, were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). A prevalence of 17.1% (CI: 14.6, 19.6) HPV DNA positivity was detected in the study population. Prevalence in oropharyngeal cases was 41.1% (CI: 34.5, 47.8); in oral cavity cases was 10.9% (CI: 7.5, 14.2); and in laryngeal cases was 7.8% (CI: 4.9, 10.7). High-risk carcinogenic HPV16 was the overwhelmingly dominant genotype amongst HPV positive cases regardless of sub-site. HPV-related oropharyngeal cases saw the highest average annual percentage change in incidence of 16.4% (p<0.0001) over the time period. Significant predictors of HPV positivity amongst all cases were younger age, oropharyngeal sub-site, and never- and ex-smoking status. HPV positive cases also presented disproportionately at later TNM stage with higher extent of nodal involvement. Both overall and cancer-specific survival were significantly improved amongst HPV positive all patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV positive patients in the oropharynx, surgery alone maximized survival, alluding to the potential for de-escalation of treatment in HPV-related OSCC in particular. Cumulatively, these findings highlight the importance of introducing boys in to the national HPV vaccination programme in Ireland, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention, two changes the Irish government will be implementing in September 2019.