Hormone factors play a favorable role in female head and neck cancer risk

Abstract

Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34–0.77). Pregnancy (OR = 0.61; 95% CI: 0.42–0.90) and giving birth (OR = 0.59; 95% CI: 0.38–0.90) at <35 years of age were inversely associated with HNCs. An inverse association with HNC was observed with age at start of HRT use (OR = 0.59; 95% CI: 0.39–0.90) for each additional 10 years and with duration of use (OR = 0.87; 95% CI: 0.76–0.99 for every 3 years). Exogenous female hormone use is associated with a nearly twofold risk reduction in female HNCs. The lower female HNC incidence may, in part, be explained by endogenous and exogenous estrogen exposures.

Treatment modality and outcomes in larynx cancer patients: A sex‐based evaluation

“…27 Additionally, estrogen may lend a protective effect (both endogenous and exogenous in the case of hormone replacement therapy) even mitigating the effects of tobacco and alcohol use. 28 Women who experience menopause (either natural or surgically induced) at a younger age (<52 y) also have a higher risk of head and neck cancer, which in part could be related to the loss of the protective effects of estrogen. 28 One large British study examining inequalities in larynx cancer in England and Wales between 1991 and 2006 found the 5-year OS in women to be 8% lower than in men.…”

“…28 Women who experience menopause (either natural or surgically induced) at a younger age (<52 y) also have a higher risk of head and neck cancer, which in part could be related to the loss of the protective effects of estrogen. 28 One large British study examining inequalities in larynx cancer in England and Wales between 1991 and 2006 found the 5-year OS in women to be 8% lower than in men. 29 Ellis et al reported lower 5-year OS in women across all three time periods of 1991-1995, 1996-2000, and 2000-2006.…”

Human papillomavirus as a driver of head and neck cancers

“…Similarly, a higher risk of HNSCC is associated with menopause onset before 52 years of age. 75 Furthermore, oestrogen-related and progesterone-related factors interact with common risk factors, such as smoking and alcohol, that are known to biologically affect female hormone pathways. Indeed, tobacco smoking increases oestrogen catabolism, 76 while liver metabolism, affected by alcohol drinking, is involved in oestrogen homoeostasis.…”

“…77 The higher oestrogen levels present in alcohol drinkers can act synergistically with the presence of endogenous/ exogenous hormones to decrease the HNSCC risk in women. 75 It is most likely, however, that there are intrinsic biochemical and molecular differences between female and male cells that have an impact on tumorigenesis, independently of sex hormones. For example, differences in the global demethylation pattern of induced pluripotent stem cells have been observed between males and females, 78 and it is well established that HPV modifies the epigenetic landscape of host cells by upregulating DNA methyltransferase 1 (DNMT1).…”

Effects of green tea on miRNA and microbiome of oral epithelium

“…Interestingly, one of these hub miRNAs, miR-181a-5p, and the 7 co-expressed miRNAs, target mRNAs associated with the estrogen receptors signaling pathway. GT catechin have been shown to both inhibit or stimulate in a concentration dependent manner, different components of the estrogen receptor signaling pathway including ER alpha itself 55 Estrogen receptor and estrogen levels are thought to be important in head and neck SCC outcomes 56 . The epidermal growth factor receptor is activated during carcinogensis in many head and neck cancers and is thought to be a key driver of that state 57 .…”