Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis

Abstract

Background/Aim: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. Materials and Methods: Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. Results: Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. Conclusion: The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.Head-and-neck cancer comprises a group of malignancies affecting multiple sites including the oral cavity, the oropharynx, nasopharynx, hypopharynx, larynx and the salivary glands. Histologically, these lesions are most commonly squamous cell carcinomas (HNSCC) (1). An estimated 650,000 new cases occur yearly worldwide, along with 330 000 deaths from HNSCC (2). In the USA, HNSCC corresponds to 3% of all cancers with approximately 53,000 new cases and 10,800 deaths yearly. Males seem to be at higher risk, with a male to female ratio varying between 2:1 and 4:1 (3). Classically, alcohol and tobacco consumption have been identified as major risk factors for developing HNSCC (4, 5). Recently, infection with high-risk human papillomavirus (HPV) has been recognized as a risk factor for developing HNSCC (6). HPVpositive HNSCC is preferentially located at oropharyngeal sites, especially the tonsils and the tongue base, and shows distinguishing clinico-pathological features (7). Other risk factors for developing HNSCC include dietary or workplace exposure to environmental toxicants and genetic predisposition (8-10). Between 2005 and 2014, the incidence of HPV-positive HNSCC increased by 3% while that of classical lesions decreased by 2% (11). The increasing incidence of HPVpositive HNSCC motivated a significant effort to understand the biopathology of these lesions and adapt the current therapeutic approaches (12). A number of markers is currently in use or under study for identifying these lesions (e.g., immunohistochemistry for p16 IN...

Six-month mortality has decreased for patients with curative treatment intent for head and neck cancer in Sweden

“…Other studies have suggested that estrogen could have a beneficial impact on survival after HNC [ 28 – 31 ], however that correlation was not analyzed here. In consistency with other studies [ 8 , 12 , 24 , 26 , 27 , 32 , 33 ], we saw that higher age and performance status correlated with an increased rate of early death.…”

Six-month mortality has decreased for patients with curative treatment for head and neck cancer in Sweden

“…Other studies have suggested that estrogen could have a beneficial impact on survival after HNC [22–25], however that correlation was not analyzed here. In consistency with other studies [8, 12, 18, 20, 21, 26, 27], we saw that higher age and performance status correlated with an increased rate of early death.…”

Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan

“…According to an analysis of scientific literature about sex hormone receptors in head and neck squamous cell carcinoma (HNSCC), ERα plays various roles in the biopathology of HNSCC, particularly oropharyngeal cancer. These include promoting DNA hypermutation, facilitating HPV integration, and cooperating with epithelial growth factor receptor (EGFR) [ 82 ]. This may explain the increased mortality of lip/oral/pharyngeal cancer in our study.…”