The role of acid and alkaline reflux in laryngeal squamous cell carcinoma

Laryngoscope. 2002 Oct;112(10):1861-5. doi: 10.1097/00005537-200210000-00030.


Hypothesis: At present, main factors considered responsible for the onset of squamous cell carcinoma are tobacco smoking, alcohol abuse, and exposure to viral and toxic agents. In last years, great interest has been focused on gastroesophageal reflux as independent carcinogenic factor and co-carcinogen in association with smoking and alcohol assumption.

Study design: Initially, the aim of this study was to objectively evaluate the presence of distal and proximal esophageal reflux with multielectrode pH measurement in patients with cancer of the larynx and/or hypopharynx (group A). However, in the course of the study, pharyngolaryngeal cancer was also observed in 4 patients with achlorhydria; therefore, the hypothesis that alkaline reflux might be involved in the onset of laryngeal cancer was tested (group B).

Methods: Twenty-one consecutive patients with laryngeal or hypopharyngolaryngeal squamous cell carcinoma (group A) entered the study. Twenty-one patients without laryngo-pharyngeal diseases were used as control subjects. A validated questionnaire of the clinical history was completed by all patients who underwent 24-hour pH monitoring. Group B included 40 consecutive gastrectomized patients (28 males and 12 females) in whom biliary or alkaline reflux was directly consequent to Billroth I or Billroth II operation. The control group was composed of 40 non-gastrectomized dyspeptic patients. The clinical history was controlled and obtained; EDGS and ENT examination with videolaryngoscopy was performed in all patients.

Results: In group A, pH measurement showed pathological reflux in 80.9% (17 of 21) of patients with no typical symptoms in 63.7% of them. The difference was significant with respect to the control group. In group B, 6 of 40 (15%) had preneoplastic lesions or a history of laryngeal tumor. The difference was significant with respect to the control group. A total of 7.5% of group B patients had previously undergone CO2 laser cordectomy for laryngeal squamous cell carcinoma and 7.5% had leukoplakia. We found a significantly higher incidence (<.05) of neoplastic and preneoplastic disease of the larynx in patients undergoing Billroth II and total gastrectomy than in those undergoing Billroth I and Roux-en-Y resection. We also found a significant increase (<.01) in ENT lesions in the group of patients who had undergone gastrectomy more than 20 years previously.

Conclusions: In agreement with literature reports, results obtained in group A confirmed that gastroesophageal reflux is often present in patients with neoplastic lesions of the pharynx and larynx. Furthermore, gastric resection is indicated for the first time as an additional risk factor or cofactor of precancerosis and squamous cell carcinoma of the pharynx or larynx. Further studies are necessary to establish the cause and effect relationship between biliary reflux and pharyngo-laryngeal tumors.

MeSH terms

  • Adult
  • Aged
  • Bile Reflux / complications*
  • Carcinoma, Squamous Cell / etiology*
  • Duodenogastric Reflux / complications
  • Duodenogastric Reflux / diagnosis
  • Esophagus / metabolism
  • Female
  • Gastrectomy / adverse effects
  • Gastric Acidity Determination
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / diagnosis
  • Humans
  • Hydrogen-Ion Concentration
  • Laryngeal Neoplasms / etiology*
  • Laryngoscopy
  • Leukoplakia / etiology
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Pharyngeal Neoplasms / etiology
  • Risk Factors
  • Smoking / adverse effects