Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between
hydrochlorothiazide (
HCTZ) exposure and skin, lip and
oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped:
squamous cell carcinoma (SCC)
skin cancer;
basal cell carcinoma (BCC)
skin cancer;
melanoma;
lip cancer and
oral cancer. Patients within the
lip cancer and
oral cancer groups were accepted with a history of non-
melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of
cancer. Patients with a history of
organ transplantation, human immunodeficiency virus (HIV) or
immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to
cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for
lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC,
melanoma,
lip cancer and
oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative
HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year
HCTZ exposure lag-time and a five-year
HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative
HCTZ exposure, the number of patients needed to treat to cause one additional
cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and
lip cancer was significantly elevated with every use of
HCTZ. Relative incidence of
melanoma and
oral cancer was not significantly elevated with
HCTZ exposure. Smoking was inversely associated with BCC and
melanoma risk, but significantly increased the risk of lip and oral cavity
cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC
melanoma and oral cavity
cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and
lip cancer in a UK population is increased with cumulative high-dose
HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.