Use of nonaspirin nonsteroidal anti‐inflammatory drugs and risk of head and neck cancer: A nationwide case–control study

• Published in: International journal of cancer 2020-04, Vol.146 (8), p.2139-2146
• Main Authors: Cour, Cecilie D., Dehlendorff, Christian, Aalborg, Gitte L., Buchwald, Christian, Friis, Søren, Verdoodt, Freija, Kjaer, Susanne K.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Cancer; Case-Control Studies; Denmark - epidemiology; Female; Head & neck cancer; head and neck neoplasms; Head and Neck Neoplasms - epidemiology; human papilloma virus; Human papillomavirus; Humans; Inflammation; Male; Malignancy; Medical research; Middle Aged; Morbidity; Nonsteroidal anti-inflammatory drugs; nonsteroidal anti‐inflammatory agents; pharmacoepidemiology; Registries
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32544

Head and neck cancer (HNC) is the sixth most frequent malignancy with high mortality and substantial morbidity and hence there is a need for identification of preventive factors. Preclinical and observational studies have reported antineoplastic effects of nonaspirin nonsteroidal anti‐inflammatory drugs (NSAIDs), but studies of nonaspirin NSAID use and risk of HNC are sparse and with inconsistent results. We therefore conducted a register‐based case–control study nested in the entire Danish population. Cases (n = 12,389) comprised all Danish residents aged 30–84 years with a histologically verified primary HNC diagnosis during 2000–2015. Based on the literature, cases were categorized into four groups of anticipated association with human papillomavirus (HPV): strong, potential, no/weak and uncertain. Age‐ and sex‐matched population controls (n = 185,835) were selected by risk‐set‐sampling. We obtained information on filled prescriptions of nonaspirin NSAIDs, other drug use, comorbid conditions and socioeconomic parameters from nationwide Danish registries. Ever‐use (≥2 prescriptions) of nonaspirin NSAIDs was not associated with the overall risk of HNC after adjustment for potential confounders (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.95–1.03). However, long‐term consistent use (≥5 years) was associated with a 25% reduction in HNC risk (OR: 0.75, 95% CI: 0.62–0.90). Stratified analyses by anticipated HPV‐association showed no material differences in estimates. In conclusion, ever‐use of nonaspirin NSAIDs was not associated with the risk of HNC with no apparent influence on the estimates by the anticipated HPV‐association. However, long‐term consistent use may be associated with a reduced risk of HNC and merits further investigation. What's new? Non‐aspirin non‐steroidal anti‐inflammatory drugs (NSAIDs) have been associated with reduced risks of certain types of cancer, but the evidence for head and neck cancer (HNC) is limited and equivocal. In this nationwide nested case–control study with inclusion of 12,389 HNC cases and 185,835 population‐based controls, long‐term consistent use (≥5 years) of non‐aspirin NSAIDs was associated with a 25% reduction in HNC risk. No risk reductions were found with ever‐use or non‐consistent use of non‐aspirin NSAIDs. These potential preventive effects must be weighed against the well‐known side effects of non‐aspirin NSAIDs, especially if used as primary prevention in otherwise healthy people.