Proton pump inhibitors and histamine 2 blockers are associated with improved overall survival in patients with head and neck squamous carcinoma

Cancer Prev Res (Phila). 2014 Dec;7(12):1258-69. doi: 10.1158/1940-6207.CAPR-14-0002.


It has been postulated that gastroesophageal reflux plays a role in the etiology of head and neck squamous cell carcinomas (HNSCC) and contributes to complications after surgery or during radiotherapy. Antacid medications are commonly used in patients with HNSCC for the management of acid reflux; however, their relationship with outcomes has not been well studied. Associations between histamine receptor-2 antagonists (H2RA) and proton pump inhibitors (PPI) use and treatment outcomes were determined in 596 patients with previously untreated HNSCC enrolled in our SPORE epidemiology program from 2003 to 2008 (median follow-up 55 months). Comprehensive clinical information was entered prospectively in our database. Risk strata were created on the basis of possible confounding prognostic variables (age, demographics, socioeconomics, tumor stage, primary site, smoking status, HPV16 status, and treatment modality); correlations within risk strata were analyzed in a multivariable model. Patients taking antacid medications had significantly better overall survival (OS; PPI alone: P < 0.001; H2RA alone, P = 0.0479; both PPI + H2RA, P = 0.0133). Using multivariable Cox models and adjusting for significant prognostic covariates, both PPIs and H2RAs used were significant prognostic factors for OS, but only H2RAs use for recurrence-free survival in HPV16-positive oropharyngeal patients. We found significant associations between the use of H2RAs and PPIs, alone or in combination, and various clinical characteristics. The findings in this large cohort study indicate that routine use of antacid medications may have significant therapeutic benefit in patients with HNSCC. The reasons for this association remain an active area of investigation and could lead to identification of new treatment and prevention approaches with agents that have minimal toxicities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Follow-Up Studies
  • Gastroesophageal Reflux / drug therapy
  • Gastroesophageal Reflux / mortality*
  • Gastroesophageal Reflux / pathology
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / mortality*
  • Head and Neck Neoplasms / pathology
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Survival Rate


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors