Exogenous Estrogen in the Development of Head and Neck Cancer

Abstract

ImportanceSex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones.ObjectiveTo assess the role of exogenous estrogen exposure in the development of HNC in female patients.Design, Settings, and ParticipantsThis large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023.Main Outcome and MeasuresDiagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI.ResultsAmong the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use.Conclusions and RelevanceThe findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

Exogenous Estrogen and Head and Neck Cancer

“…To the Editor We read with great interest the article from Doll et al This study showed that oral contraceptives (OCs) are associated with increased risk of head and neck cancer (HNC), while hormone replacement therapy (HRT) was associated with decreased risk of HNC. To further elucidate the findings and enhance the robustness of the conclusions, we would like to propose several recommendations for consideration.…”

“…The authors did not explicitly deliberate the management of cases where individuals ceased HRT for personal reasons. Besides, the definition of OC/HRT user is unclear in the Methods section . We would like to know whether the authors define OC/HRT user by Anatomical Therapeutic Chemical code or documentation in medical records.…”

Exogenous Estrogen and Head and Neck Cancer—Reply

“…In Reply We are pleased with the ongoing scientific discussion on the role of oral contraceptives (OCs) and hormone replacement therapy (HRT) in the development of head and neck cancer (HNC) . We have read with great interest 2 Letters to the Editor by Lin et al and Yang et al and would like to address the concerns raised.…”

Exogenous Estrogen and Head and Neck Cancer

“…To the Editor We read with great interest the article by Doll et al regarding exogenous estrogen in the development of head and neck cancers. We appreciated the results of this cohort study that head and neck cancer prevalence may be higher in female patients taking oral contraceptives and lower in female patients taking hormone replacement therapy.…”