Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis

Eur J Clin Pharmacol. 2022 Jun;78(6):919-930. doi: 10.1007/s00228-022-03299-x. Epub 2022 Mar 8.


Purpose: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development.

Methodology: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0).

Results: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg.

Conclusions: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Keywords: Carcinoma squamous cell; Diuretics; Hydrochlorothiazide; Nonmelanoma skin cancer; Photosensitising reaction; Skin cancer.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell* / chemically induced
  • Carcinoma, Squamous Cell* / complications
  • Carcinoma, Squamous Cell* / epidemiology
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects
  • Lip / pathology
  • Lip Neoplasms* / chemically induced
  • Lip Neoplasms* / complications
  • Lip Neoplasms* / epidemiology
  • Male
  • Skin Neoplasms* / chemically induced
  • Skin Neoplasms* / epidemiology


  • Hydrochlorothiazide