Sex Disparity for Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review

Abstract

The incidence of head and neck cutaneous squamous cell carcinoma (HNcSCC) is unevenly distributed between men and women. At present, the mechanism behind this disparity remains elusive. This study conducted a systematic review and meta-analysis of proportions to investigate the disparity between sexes for patients with HNcSCC. PubMed, Scopus, EMBASE, MEDLINE, Emcare and CINAHL were searched in November 2021 and June 2022 (N > 50, English, human), and studies which examined the association between sex and HNcSCC were included. Analysis was conducted using RStudio with data and forest plots displaying males as a proportion of total patients with HNcSCC. Two independent researchers performed study selection, data extraction, data analysis and risk of bias. Eighty-two studies (1948 to 2018) comprising approximately 186,000 participants (67% male, 33% female) from 29 countries were included. Significantly more males had HNcSCC overall (71%; CI: 67–74). Males were also significantly more affected by cSCC of the ear (92%; CI: 89–94), lip (74%; CI: 66–81), and eyelid (56%; CI: 51–62). This study found HNcSCC disproportionately affected males overall and across all subtypes. Improving our understanding of sex-specific mechanisms in HNcSCC will better inform our preventive, therapeutic and prognostic practices.

A retrospective analysis of drugs associated with the development of cutaneous squamous cell carcinoma reported by patients on the FDA’s adverse events reporting system

“…[19][20][21] Cases of cSCC in the general population indicate that it is more prevalent in males than females. 22 However, this is likely because men spend more time exposed to the sun without adequate protection. 23,24 Similarly, our investigation found that reports of cSCC as an adverse event to medications were overall most prevalent amongst males; however, in certain medication classes, such as monoclonal antibodies, cSCC was more prevalent in females.…”

A retrospective analysis of drugs associated with the development of cutaneous squamous cell carcinoma reported by patients on the FDA’s adverse events reporting system

“…Cases of cSCC in the general population indicate that it is more prevalent in males than females [ 22 ]. However, this is likely because men spend more time exposed to the sun without adequate protection [ 23 , 24 ].…”

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

“…46,47 Further, none are derived from a female; while males are more predominately affected by metastatic cSCC, there is increasing suggestion of a sex-related influence on disease progression requiring greater preclinical representation. 48,49 These limitations are compounded by the time to establish these cell lines by clonal outgrowth, followed by a minimum of four but usually beyond 10 passages. 13,14 This is notwithstanding the laborious efforts to comprehensively validate the cell lines to facilitate meaningful correlations between tumour properties and therapeutic sensitivity for responder stratification.…”

“…Given distinct differences in the molecular alterations and TME characteristics of tumours of immunocompromised compared to immunocompetent patients, comprehensive screening of both cohorts is critical 46,47 . Further, none are derived from a female; while males are more predominately affected by metastatic cSCC, there is increasing suggestion of a sex‐related influence on disease progression requiring greater preclinical representation 48,49 . These limitations are compounded by the time to establish these cell lines by clonal outgrowth, followed by a minimum of four but usually beyond 10 passages 13,14 .…”