Evidence suggests that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have antineoplastic properties of potential importance for survival of head and neck cancer.
We conducted a nationwide cohort study including all individuals with primary head and neck squamous cell carcinoma in Denmark during 2000–2016 at age 30–84 years, with no history of cancer (except non-melanoma skin cancer), and alive at 1 year after diagnosis. Nationwide registries provided information on drug use, causes of death and potential confounders, and additional clinical information was obtained for a subpopulation. We conducted Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between post-diagnosis non-aspirin NSAID use (defined as ≥1 filled prescription within first year after diagnosis) and cancer-specific mortality.
Among 10,770 head and neck cancer 1-year survivors, the HR for cancer-specific mortality with non-aspirin NSAID use was 1.68 at 1 year after diagnosis, but declined and stabilized around 1.15 (95% CI 1.02–1.29) at 2 years after diagnosis. Among 2-year survivors, the HRs for cancer-specific mortality with non-aspirin NSAID use remained slightly increased in analyses stratified by age, sex, stage, and pre-diagnosis non-aspirin NSAID use. Similar results were seen in the subpopulation (n = 1029) with additional clinical information, and among 5-year survivors with additional non-aspirin NSAID exposure assessment.
In this nationwide cohort of patients with head and neck cancer, use of non-aspirin NSAIDs was associated with a slightly increased mortality risk, warranting further evaluation.
Non-aspirin (NA)-NSAID use has been suggested to reduce head and neck cancer mortality.
This nationwide cohort study found a slightly increased mortality with NA-NSAIDs.
The increased mortality with NA-NSAIDs persisted across age, sex and stage.
No clear trends were found according to patterns of use or COX-2-selectivity.
Globally, squamous cell carcinoma (SCC) of the head and neck (HNSCC) constitute the seventh most common cancer group and a major cause of cancer mortality, with an estimated 890,000 new cancer cases and 450,000 cancer deaths worldwide in 2018 . Although survival of HNSCC has improved over the last decades, the overall 5-year relative survival of patients with HNSCC in Denmark was only 66% in 2018 . Identification of measures that could improve survival in patients with HNSCC is therefore needed.
Non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) are commonly used for pain relief and inflammatory conditions . NSAIDs have been hypothesized to possess antineoplastic properties due to inhibition of the enzyme cyclooxygenase (COX)‐2, which is overexpressed in inflamed tissue and malignant cells of several cancer types . Upregulated levels of COX-2 have also been found in HNSCC and are associated with increased cell proliferation, promotion of angiogenesis, metastatic invasion, and poor prognosis .
Preclinical studies have shown that NA-NSAIDs inhibit growth and induce apoptosis in HNSCC cell lines and decrease HNSCC tumor growth and mortality in laboratory animals . Previously, we found indications of a protective effect of long-term consistent use of NA-NSAIDs against development of HNSCC . However, the few observational studies that have examined mortality after HNSCC with NA-NSAID use have reported inconsistent results . Evaluation of exposure patterns and identification of potential differential effects according to patient characteristics is limited.
This prompted us to investigate the association between NA-NSAID use and cancer-specific mortality among patients with HNSCC, based on data from nationwide Danish registries providing accurate individual-level information of high coverage.