IJC International Journal of Cancer
Trends in head and neck cancer incidence in Denmark, 1978–2007: focus on human papillomavirus associated sites Maria Blomberg1, Ann Nielsen1, Christian Munk1 and Susanne Kru¨ger Kjaer1,2 1 2
Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark Gynaecological Clinic, Rigshospitalet, University of Copenhagen, Denmark
Introduction The term head-and-neck cancer (HNC) covers a broad spectrum of anatomical sites, most of which are considered to be relatively rare in comparison with other malignant tumors. Nevertheless, in 2008 HNC was the fifth commonest cancer in men and the eleventh commonest in women in Denmark.1 These cancers are found predominantly in men, but the male: female ratio varies worldwide and by anatomical site. There is no consensus about which sites to include under the term ‘‘HNC,’’ but the lip, oral cavity, salivary glands, tonsils, oropharynx, nasopharynx, hypopharynx, nasal cavity, middle ear, paranasal sinuses, larynx and thyroid can be included. As the thyroid differs considerably from the other sites, it is often excluded in both clinical and epidemiological reports of HNC. Morphologically, squamous cell carcinomas predominate. HNC mortality depends on the location and stage of the tumor at diagnosis. Survivors of HNC often have longterm side-effects of surgery or radiation, which affect their quality of life. Long-term sequelae involves emotional, social and physical disabilities, including disfigurement, Key words: Head-and-neck cancer, human papillomavirus, Denmark, squamous cell carcinoma, epidemiology DOI: 10.1002/ijc.25699 History: Received 18 May 2010; Accepted 8 Sep 2010; Online 28 Sep 2010 Correspondence to: Susanne Kru¨ger Kjaer, Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark, Fax: þ45 35257731, E-mail:
[email protected]
C 2010 UICC Int. J. Cancer: 129, 733–741 (2011) V
motor and sensory nerve damage, eating difficulties, caries, xerostomia, dysphagia, weight loss and cutaneous fibrosis. In many patients, the tumors are diagnosed when they are young. The impact on public health costs of young age at diagnosis and long-term effects after curative treatment is substantial. The well-known risk factors for HNC are tobacco and alcohol use, which acts synergistically, but also poor oral hygiene is regarded a possible risk factor for oral cavity cancer.2 Oral and oropharyngeal cancers are therefore most commonly seen in countries where tobacco and alcohol consumption are high, including southern Africa, Australia, Brazil, France, India, The Netherlands, Papua-New Guinea and Switzerland.3 In line with this the overall HNC rates have decreased in the US where tobacco and alcohol use is declining.4 Epidemiological studies worldwide have shown, however, increasing trends in the incidence of HNC at specific sites, despite the declining use of tobacco.5–7 These findings suggest that other etiological factors are involved, and high-risk types of human papillomavirus (HPV) have been reported to be risk factors for oral and oropharyngeal cancer.8,9 The aim of our study was to assess the overall incidence of HNC among Danish men and women in 1978–2007, to describe the distribution and trends in incidence rates of HNCs at specific anatomical sites and to assess whether the incidence of cancers possibly associated with HPV infection is increasing. Previous studies of HNC incidence addressed trends in the incidence of tumors at one site (often tonsils),7,10–12 from only one region of a country,6,10,12,13 or during a shorter period.5,6,12–14 We examined the nationwide trends for HNCs overall and for 11 specific sites over a 30-year period.
Epidemiology
The aim of our study was to assess the overall trends in the incidence of head-and-neck cancer (HNC) among Danish men and women in 1978–2007, to describe the distribution and incidences of HNCs at different anatomical sites, and to determine whether the incidence of human papillomavirus (HPV)-associated cancers is increasing. Data were extracted from the nationwide Cancer Registry database. To assess the possible impact of HPV infection, the sites of squamous cell carcinomas were categorized as HPV-associated, potentially HPV-associated or HPV-unrelated. In total, 26,474 incident cases were identified and the overall incidence increased throughout the period. Significantly increasing incidence rates were notably seen for tumors in the oral cavity (2.2% per year), tonsils (4.8% per year), oropharynx (3.5% per year) and hypopharynx (4.4% per year). A significantly decreasing incidence of lip cancer was observed among men (–5.0% per year). Cancers at HPV-associated sites (n 5 3650) showed strongly increasing incidence rates, primarily in individuals < 60 years. In contrast, HNCs at sites not related to HPV infection showed a significant decrease (in men) or virtually no change in incidence (in women). Our results suggest a marked impact of HPV infection on the epidemiology of HNCs in Denmark. HPV16 is the type most often found in HNCs; thus, the recent introduction of vaccination against HPV may in the future prevent HPV-associated cancers of the head and neck.
734
Head-and-neck cancer and HPV infection in Denmark
Table 1. Classification of head-and-neck cancers (ICD-10) by anatomical site and in relation to the anticipated strength of association with human papillomavirus (HPV) infection, Denmark, 1978–2007 All HNC (n 5 26 474)1
Anatomical sites of HNCs and ICD-10 code
Squamous cell HNCs and code in relation to strength of association with HPV (n 5 23 466)
C00-C14
Lip
C00
HPV-associated:
Oral cavity
C01-C06
Tonsils incl. Waldeyer ring
C09, C14.2
Salivary glands
C07-C08
Base of tongue and lingual tonsil
C01.9, C02.4
Tonsils
C09
Other oro-pharyngeal sites
Oro-pharynx
C10
Naso-pharynx
C11
Hypo-pharynx
C12-C13
C30-C32
C02.8, C10.2, C10.8, C10.9, C14.0, C14.8
Potentially HPV-associated: Tongue
C02.0-C02.3, C02.9
Others (lip, oral cavity, pharynx)
C14
Other oral cavity sites
C03, C04, C05.0, C06
Nasal cavity, middle ear
C30
Larynx
C32
Sinuses
C31
Other oro-pharyngeal sites
Larynx
C32
C05.1, C05.2, C05.8, C05.9, C10.0, C10.1, C10.3
Potentially unrelated to HPV Remaining HNC sites
C00, C07, CO8, C10.4 C11-13, C14.1, C30, C31
1
Except lymphomas, sarcomas and others (n ¼ 1298).
Epidemiology
Material and Methods Cases of HNC were identified from the population-based Danish Cancer Registry database, which covers the entire Danish population of 5.5 million (2009).15 Since 1943, hospitals, general practitioners and specialists have reported all new cancer cases to the database. It contains information on virtually all newly diagnosed cases, including topography, morphology, date of diagnosis and birth date of each patient. To ensure that registration is as complete as possible, the Cancer Registry is continuously supplemented with information from the Causes of Death Registry and the National Patient Registry. Since 1978, HNCs have been classified by both topography and histological type, and we therefore studied the incidence trends from 1978 to 2007. The study was approved by the Danish Data Protection Agency.
Identification and classification of HNCs
To identify cases of HNC in 1978–2007 we extracted categories C00–C14 and C30–C32 of the International Classification of Diseases, 10th edition (ICD-10) (Table 1). Information about morphology was available from the International classification of diseases for oncology (ICD-O) morphology codes. Only invasive cancers were included (i.e., with three as the last digit). We excluded lymphomas, sarcomas (including Karposi sarcoma) and a few other tumors (primarily nerve tumors), with ICD-O3 codes 8800–8936, 8950–9110, 9120, 9124, 9130, 9140 and 9170–9948. The HNCs were then grouped into 11 anatomical sites: lip, oral cavity, salivary glands, tonsils, oropharynx, nasopharynx, hypopharynx, nasal cavity including middle ear, sinuses, larynx, etc. (lip, oral cavity, pharynx) (Table 1).
All HNC cases of squamous cell origin (morphology codes 8050–8084, 8120–8131) were classified into three groups: The first two groups, the HPV-associated sites and the potentially HPV-associated sites, were created based on the classification made by Ryerson et al.5 (Table 1). They defined the HPVassociated sites as those reported as being associated with HPV in previous studies. Cancers of the potentially HPVassociated sites, Ryerson et al. chose on the basis of their anatomical similarity to the cancers in the first group, even though an association with HPV infection has not yet been established. Finally we created a third group, the HPV-unrelated sites. This group consisted of the remaining sites, which we assumed were unrelated to HPV infection (Table 1). Statistical analyses
Incidence rates were reported as numbers of new cases per 100,000 person–years, and they were age-standardized according to the 2000 standard world population.16 Incidence rates were calculated by 5-year periods according to gender and age (60 years (APC, 0.0%), while no difference was noted for women (APC
