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Reflux linked to head and neck cancers in elderly
Elderly patients with gastroesophageal reflux disease showed a higher risk for malignancies of the upper aerodigestive tract in a recent case-control study.
“Population-level data suggests a link between gastroesophageal reflux disease and cancer of the throat and sinuses in adults over 65 years of age,” Edward D. McCoul, MD, MPH, of the department of otolaryngology, head and neck surgery, at Tulane University School of Medicine, and the Ochsner Clinic Foundation in New Orleans, told Healio Gastroenterology and Liver Disease. “The strength of association between reflux and cancer is strongest for anatomic sites closest to the esophagus, where acid and other stomach contents may have the greatest exposure.”
Prior studies on the link between GERD and malignancies of the upper aerodigestive tract (UADT) have produced conflicting results, and studies in older patients are lacking, McCoul and colleagues wrote.
Therefore, they reviewed SEER data from 2003 through 2011 on 27,610 Medicare recipients (median age, 74 years; 75.24% men), 13,805 of whom had a malignancy of the larynx (60.5%), hypopharynx (5.4%), oropharynx (5.2%), tonsil (14.4%), nasopharynx (5.5), or paranasal sinuses (9%). Researchers compared GERD rates between these cancer patients and a random sample of Medicare recipients without cancer matched by age, sex and year of diagnosis.
They found that patients with GERD showed a greater risk for developing malignancies of the larynx (adjusted odds ratio [aOR] = 2.86; 95% CI, 2.65-3.09), hypopharynx (aOR = 2.54; 95% CI, 1.97-3.29), oropharynx (aOR = 2.47; 95% CI, 1.90-3.23), tonsil (aOR = 2.14; 95% CI, 1.82-2.53), nasopharynx (aOR = 2.04; 95% CI, 1.56-2.66), and paranasal sinuses (aOR = 1.4; 95% CI, 1.15-1.70). The risk was lowest for cancers of the paranasal sinuses and highest for cancers of the larynx.
McCoul and colleagues also noted the associations remained significant even when they accounted for GERD exposure time.
They concluded that the data suggest elderly patients with GERD are 3.47 times more likely to receive a diagnosis of laryngeal cancer, 3.23 times more likely to receive a diagnosis of hypopharyngeal cancer, 2.88 times more likely to receive a diagnosis of oropharyngeal cancer and 2.37 times more likely to receive a diagnosis of tonsillar cancers in the U.S.
While these results indicate an opportunity for earlier detection and intervention, future research should evaluate these associations in younger patients and evaluate their underlying causes, they noted.
“It is important to point out that a causative link cannot be established from this type of data,” McCoul said. “It is unclear what effect acid exposure may have on tumor development, although chronic inflammation is a possibility. Further research should focus on assessing these associations in a younger population and investigating mechanisms of causation.” – by Adam Leitenberger
Disclosures: The authors report no relevant financial disclosures.
Perspective
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The development of esophageal carcinoma has been attributed to chronic inflammation due to gastroesophageal reflux. Could gastroesophageal reflux also cause malignancies further up in the aerodigestive tract, such as in the larynx, oropharynx or even the paranasal sinuses? This is the question that the investigators ask in this case control study using Medicare-linked data from the SEER database.
This is not the first study to investigate this question, but it is the largest, with 27,610 elderly patients with head and neck cancer compared with a control group of 13,805 patients without head and neck cancer. GERD was associated with greater odds of developing cancers in a variety of head and neck sites. For any head and neck subsite, the odds of developing a cancer increased with proximity to the esophageal inlet. Consequently, GERD was associated with a greater increase in the odds for developing larynx and hypopharynx cancer (2.5- to 3-fold) than paranasal sinus cancer (1.5-fold). Further, the odds of developing cancer also increased with the duration of GERD prior to diagnosis, independent of potential cofounders. The presence of GERD for less than 12 months was associated with a less than 1.5-fold increased odds of developing tonsil cancer; GERD for over 2 years was associated with a greater than fourfold increased odds of developing tonsil cancer.
There are some provocative findings in this study that support the notion that airway inflammation caused by GERD promote the development of head and neck cancers. GERD is more strongly associated with the development of cancers closer anatomically to the esophageal inlet. Additionally, the duration of GERD is positively associated with the risk for developing cancer. Taken together, these observations suggest but don’t prove a causal relationship.
The limitations of the study cast doubt on this conclusion, however. The study fails to account for well-known risk factors for head and neck cancer, such as smoking history. Smoking history is not collected by SEER or Medicare, and could not be included in the analysis. However, a previous study that evaluated the effect of GERD on risk for head and neck cancer showed that when smoking history was included, associations between GERD and cancer risk lost significance. It’s possible that GERD is merely a confounder rather than an independent factor or cofactor. A higher risk for cancer is attributable to greater tobacco exposure in individuals with GERD, rather than the inflammation from GERD itself.
It’s important to remember that GERD is very common, affecting 10% to 30% of the population. In contrast, head and neck cancers are rare. Even among the elderly who are considered at higher risk, the odds of developing such cancers are small. For the time being, screening individuals with GERD for head and neck cancer is premature. Persistent hoarseness, sore throat, a neck mass, dysphagia should prompt otolaryngology referral. Tobacco cessation should remain a priority. GERD symptoms should be managed by means of established, evidence-based recommendations.