Elsevier

European Journal of Cancer

Volume 51, Issue 15, October 2015, Pages 2130-2143
European Journal of Cancer

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study

https://doi.org/10.1016/j.ejca.2015.07.043Get rights and content

Abstract

Background

Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time.

Methods

We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999–2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site.

Results

Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999–2001 to 2005–2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx).

Conclusions

This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.

Introduction

Head and neck (H&N) cancers accounted for an estimated number of 140,000 new cases and 63,500 deaths in Europe in 2012, about 4% of all cancers arising in Europe [1]. Men have a four times higher risk having a H&N cancer comparing to women [1]. In Europe, the oral cavity and pharyngeal cancers mortality reached a peak during the nineties thereafter clearly reduced, while mortality for laryngeal cancers started to decline in the early eighties reaching very low rates in 2010. The positive trends were more clear for men [2].

H&N cancers are a heterogeneous group of tumour entities anatomically close to each other, but different in terms of aetiology, histology, diagnostic and treatment approaches. About 91% of all H&N cancer are squamous cell carcinomas, 2% are sarcomas and the other 7% are adenocarcinomas, melanomas and not well specified tumours [3]. H&N cancers are mainly associated with tobacco and alcohol use [4]. Other known risk factors are human papillomavirus (HPV) [5] and Epstein-Barr virus (EBV) infections [6], and low consumption of fruit and vegetables [7]. Despite declining smoking prevalence in Europe [8], incidence of epithelial cancers of nasopharynx, hypopharynx and larynx incidence remained quite stable, while those of oropharynx and oral cavity statistically increased [3].

Previous studies on H&N cancers survival showed disparities across Europe [9], [10], with the lowest and the highest figures observed for Eastern and Northern Europe, respectively. Interestingly, differences in anatomical distribution explained a considerable portion of the survival differences by country for patients with H&N cancers. In fact, H&N sub-sites are important determinants of prognosis: among mouth–pharynx sites, hypopharynx, base of tongue, lateral and posterior wall of the oropharynx are characterised by relatively poor survival, while among laryngeal sites, the supraglottic and subglottic sub-sites have poor survival. Due to differing risk factor prevalence, the distribution of sub-sites in European countries is not homogeneous. Incidence of oral cavity and oropharyngeal cancers are lower in the United Kingdom (UK) and Ireland and the Northern countries and higher in the Eastern and Southern European countries [11], [12].

There are other well-established risk factors which are also prognostic factors. It has been shown that H&N cancer related tumours of HPV infection, e.g. tongue base, tonsil and oropharynx, [13] have better prognosis compared with the other H&N sites. The high consumption of fruit and vegetables has been associated with better prognoses for laryngeal [14] and hypopharyngeal cancers [15]. Also, smoking was recognised to influence the efficacy of treatment [16], [17]. Furthermore, for H&N cancer patients, there is a marked socioeconomic gradient in survival between affluent and deprived patients. Survival is substantially higher in more affluent men than in the more deprived [18], [19].

Nasopharyngeal cancer, which is related to viral exposure, is a rare disease in Europe, while is endemic in Southeast Asia. EBV is, together with smoke, alcohol and wood dust related occupations, among the well known risk factors for this tumours [6], [20].

The EUROCARE-5 study assessed cancer survival in the largest European population so far, with a much greater participation of cancer registries from Eastern Europe with respect to previous studies. In this study we analyse survival for patients with H&N cancers (nasal cavities, thyroid and salivary glands excluded) and diagnosed up to the end of 2007 in populations covered by population-based cancer registries participating in EUROCARE-5 [21], in relation to tumour site and sub-site as prognostic factors. Our aim is to assess whether survival differences between countries have changed, and to investigate whether H&N cancer survival changed from previous periods.

Section snippets

Materials and methods

The analysis included first and subsequent malignant H&N cancers diagnosed in adults (age ⩾15 years) up to the end of 2007 and followed up until 31st December 2008. We included tongue and lingual tonsil (topography codes C01–C02), oral cavity (C03–C06), oropharynx and tonsil (C09–C10), nasopharynx (C11), hypopharynx (C12–C13) and larynx (C32) and all H&N tumours combined except larynx (C01–C06, C09–C13). For brevity the first and the third entity will be named ‘tongue’ and ‘oropharynx’ along the

Results

Table 1 shows two indicators of quality of diagnosis: microscopically verified (MV) and unspecified sub-site for larynx (NOS, C32.9) cases. For most countries (except Wales, Croatia, Latvia and Poland), 95% or more cases were MV and about 28% of laryngeal cases were classified as located in a not well defined sub-site of the larynx. Their proportions were more that 70% in Finland, Croatia and Poland.

Five-year age-standardised RS was the poorest for hypopharynx and the highest for larynx

Discussion

During the period 1999–2007, 5-year survival for patients with oral cavity, oropharyngeal and hypopharyngeal cancer significantly improved by 3–5% (absolute difference), while for larynx it remained stable.

Over the last decade, there has been a substantial improvement in diagnosis, staging and treatment of patients with H&N cancers, and overall the natural history of H&N cancers has also evolved. Current management based on multimodality approach, is still quite complex, and often deals with

Role of funding source

Compagnia di San Paolo, Fondazione Cariplo Italy, Italian Ministry of Health (Ricerca Finalizzata 2009, RF-2009-1529710) and European Commission for two projects: (i) European Action Against Cancer, EPAAC, Joint Action No 20102202, and (ii) ‘Information network on rare cancers’, Grant No. 2000111201.

The funding sources had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Conflict of interest statement

None declared.

Acknowledgements

We thank Riccardo Capocaccia for the data interpretation and comments; Lucia Buratti, Chiara Margutti, Simone Bonfarnuzzo and Camilla Amati for secretarial assistance.

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    Sources of support (grants): Compagnia di San Paolo, Fondazione Cariplo Italy, Italian Ministry of Health (Ricerca Finalizzata 2009, RF-2009-1529710) and European Commission for two projects: (i) European Action Against Cancer, EPAAC, Joint Action No 20102202, and (ii) ‘Information network on rare cancers’, Grant No. 2000111201.

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