Population-based evidence of increased survival in human papillomavirus-related head and neck cancer

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Abstract

Background

Evidence from clinical, population-based and molecular studies has shown that human papillomavirus (HPV) infection can be a causal risk factor for a subset of head and neck squamous cell carcinomas (HNSCC). It is proposed that HPV-associated oropharyngeal cancer is a new disease entity that requires treatment and prevention strategies distinct from present recommendations.

Methods

In our population-based study we estimated incidence and survival trends in 8270 patients with HPV-related HNSCC (HPV+HNSCC) and HPV-unrelated HNSCC (HPVHNSCC) in Norway over the past three decades.

Results

In the period 1981–1995, patients with HPV+HNSCC had poorer survival than HPVHNSCC (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.14–1.44). By 1996–2007, survival had increased in both groups, but the increase was significantly greater among HPV+HNSCC patients (HR 0.57, 95% CI: 0.48–0.67). During the same period, incidence also increased, but only for HPV+HNSCCs. From 1981–1995 to 1996–2007, median age at diagnosis for HPV+HNSCC decreased from 63.2 to 59.8 years, while for HPVHNSCC median age at diagnosis of 66.6 years remained unchanged.

Conclusions

We demonstrate a population level improvement in survival among patients with oropharyngeal squamous cell cancers commonly related to infection with HPV. In contrast, patients with HNSCC not related to HPV only showed a modest improvement in survival in the period 1981–2007. A concomitant increase in incidence and survival was observed for HPV-related cancers only. This trend cannot be explained by changes in treatment, cancer registration nor screening, but is most likely due to an increased prevalence of HPV-positive tumours.

Introduction

Recently, an increase in the incidence of oropharyngeal cancer has been observed in Europe and the United States (US).1, 2, 3, 4 In Norway, oropharyngeal cancer rates exhibited a mean annual increase of 5% in contrast to declining trends of tumours of other pharyngeal sites.5 Increased exposure to infection with high-risk human papillomavirus (HPV) types and reduced exposure to tobacco in the population have been proposed as explanations.

Prognosis for the heterogenic group of pharyngeal cancers is relatively poor, with a five-year relative survival rate of about 30% in Norway in the diagnostic period 1999–2003.6 Of particular interest, however, is the fact that patients with detectable HPV in their oropharyngeal tumors have been observed to have 1.4–2.7 times better survival relative to same-tumour patients tested negative for HPV.7, 8, 9

Among head and neck squamous cell carcinomas (HNSCC), HPV DNA is most readily detected in oropharyngeal tumours.10, 11 The proportion of oropharyngeal cancers containing HPV DNA ranges from almost two-thirds to 90%.10, 12 Oropharyngeal cancers diagnosed in the last decade have been shown to harbour HPV DNA two to four times more frequently than such cancers diagnosed in the 1970s.9, 12, 13 HPV type 16 was the most commonly detected of 15 oncogenic HPV types,14 being found in 90–95% of HPV-positive cancers. Based on data emerging from clinical and microbiological studies, it has been suggested that HPV-positive HNSCCs are a distinct biological entity.2, 15, 16

In the current study we are using data from the population-based Cancer Registry of Norway and describe time trends in oral, pharyngeal and laryngeal cancer incidence rates and survival proportions over the period 1981–2007, dichotomised into categories that recognise subsites, on the basis of existing epidemiological evidence, as being broadly HPV-related or HPV-unrelated HNSCCs.

Section snippets

Material and methods

Incident cases of HNSCC extracted from the national, population-based Cancer Registry of Norway in 1981–2007 were categorised as HPV-related (HPV+HNSCC) or HPV-unrelated (HPVHNSCC).16, 17 Cancers of the base of tongue, tonsils and oropharynx (International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD 10): C01,C09–10), all oropharyngeal sites according to the TNM Classification,18, 19 were defined as HPV+HNSCC, and cancers of mobile tongue, floor of

Results

Fig. 1 shows the age-specific all cause survival proportions together with a number of patients alive at the beginning of each follow-up year, separately for patients with HPV+HNSCC (panels A and B) and HPVHNSCC (Panels C and D), in 1981–1995 (panels A and C) and 1996–2007 (panels B and D). Median age at diagnosis for HPV+HNSCC patients was 63.2 years in 1981–1995, and 59.8 years in 1996–2007. For HPVHNSCC patients, median age at diagnosis was 66.6 years in both periods. The proportion of

Discussion

Our population-based study provides further evidence that anatomic sites of the mouth and oropharynx acquired different risk profiles with respect to cancer over the past three decades in Norway. Given the concomitant increase in the incidence of and survival from oropharyngeal cancer, our results support the notion of an emerging and distinct group of head and neck cancers located within oropharynx. Cancers of the base of the tongue, tonsils and oropharynx are known to be common aetiological

Conflict of interest statement

None declared.

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